SCIENTIFIC REPORT 2018-2019

RESEARCH CENTER FOR INFECTIOUS DISEASES (ZINF) ZINF NUMBERS ABOUT THE ZINF 2018-2019

The Research Center for Infectious Diseases (ZINF) is a MULTI-DISCIPLINARY NETWORK of researchers in Würzburg addressing molecular principles of host-pathogen interactions. It brings together experts from , PARASITOLOGY, , , CHEMISTRY, and CLINICAL PRACTICE and facilitates cross-faculty communication, initiation of joint research activities, as well as recruitment of extramural funding.

-V\UKLKPU ^P[OÄUHUJPHSZ\WWVY[MYVT[OL-LKLYHS4PUPZ[Y`VM9LZLHYJOHUK ;LJOUVSVN`HUK HM[LY^HYKZ [OL )H]HYPHU :[H[L 4PUPZ[Y` MVY 9LZLHYJO HUK (Y[ [OL ZINF represents the OLDEST ACADEMIC INSTITUTION in Germany devoted to interdisciplinary research on infectious diseases. With 35 professors in infection biology, infectious diseases research is a key area of biomedical research at the Julius 4H_PTPSPHUZ YaI\YN 14< ;OL A05- NYLH[S` ILULÄ[Z MYVT Z[YVUN PU[LYHJ[PVUZHJYVZZMHJ\S[PLZJSPUPJZHUKYLZLHYJOPUZ[P[\[PVUZV\[ZPKL[OL14<

( JVYL JVTWVULU[ VM [OL A05- OHZ ILLU P[Z YOUNG INVESTIGATOR GROUP WYVNYHT [OH[ VќLYZ H \UPX\L LU[Y` MVY `V\UN YLZLHYJOLYZ PU[V [OLPY V^U ZJPLU[PÄJ career. Research of the independent ZINF junior groups covered in the period of this report focuses on organoids as new infection models, high-throughput technologies [VZ[\K`[OLTVKLVMHJ[PVUVMHU[PIPV[PJJVTIPUH[PVUZYLN\SH[VY`95(TVSLJ\SLZPU anaerobic pathogens and in the microbiome, structural biology of mycobacteria, as well as the role of the microbiota in fungal infections.

;OLA05-PZHJLU[YHSZJPLU[PÄJMHJPSP[`VM[OL14<> YaI\YNHUKOHZL]VS]LKPU[VHU internationally recognized and accredited institution.

2 3 3.5 DEPARTMENT OF MICROBIOLOGY, THEODOR BOVERI INSTITUTE, BIOCENTER 64 CONTENT Thomas Rudel - Infection Biology of Bacteria 66  4HY[PU-YH\UOVSa*LSS\SHY4PJYVIPVSVN`   9V`.YVZZ7LY[\ZZPZ  ZINF SCIENTIFIC REPORT 2018-2019 Vera Kozjak-Pavlovic - Bacterial Invasion and Intracellular Survival 69

3.6 DEPARTMENT OF INTERNAL II 70 1. GENERAL REMARKS Hermann Einsele - Interaction of Aspergillus fumigatus ^P[O/\THU5H[\YHS2PSSLY*LSSZHUK+LUKYP[PJ*LSSZ   (UKYLHZ)LPSOHJR,_WLYPTLU[HS:[LT*LSS;YHUZWSHU[H[PVU  1.1 Speaker‘s Report / Bericht der Sprecherin 10  /HY[^PN2SPURLY+P]PZPVUVM0UMLJ[PV\Z+PZLHZLZ  1.2 Structure of the ZINF 14  1 YNLU3€ўLY0TT\UP[`HNHPUZ[AspergillusZWW  1.3 Events surrounding the ZINF 16

3.7 INSTITUTE OF SYSTEMS IMMUNOLOGY 76 2. YOUNG INVESTIGATOR GROUPS OF THE ZINF  .LVYN.HZ[LPNLY;PZZ\L0TT\UP[`   4LYJLKLZ.VTLaKL(N LYV/VZ[4PJYVIPHS0U[LYHJ[PVUZ   :PUH)HY[MLSK6YNHUVPKZHZ/VZ[4VKLSZ   4HY[PU=HL[O4L[HIVSPZTHUK0TT\UL*LSS:PNUHSSPUN   (UH9P[H)YVJOHKV:`Z[LTZ)PVSVN`VM(U[PIPV[PJ(J[PVU   -YHUaPZRH-HILY95()PVSVN`VM*SVZ[YPKPVPKLZKPѝJPSL   :LIHZ[PHU.LPILS:[Y\J[\YHS)PVSVN`VM4`JVIHJ[LYPH  3.8 HELMHOLTZ INSTITUTE FOR RNA-BASED INFECTION RESEARCH 82 Christian Perez - Regulatory Networks in Pathogenesis 30  3HYZ)HYX\PZ[0U[LNYH[P]L0UMVYTH[PJZMVY0UMLJ[PVU)PVSVN`   *OHZL)LPZLS95(:`U[OL[PJ)PVSVN`   5L]H*HSPZRHU9LJVKPUN4LJOHUPZTZPU0UMLJ[PVUZ   4H[OPHZ4\UZJOH\LY+LJVKPUN95(7YV[LPU0U[LYHJ[VTLZVM9LN\SH[VY`95(PU0UMLJ[PVU  3. MEMBERS OF THE ZINF  (U[VPUL,TTHU\LS:HSPIH:PUNSLJLSS(UHS`ZPZ 3.1 INSTITUTE OF MOLECULAR INFECTION BIOLOGY 34  9LKTVUK:T`[O.LUVTL(YJOP[LJ[\YLHUK,]VS\[PVUVM95(=PY\ZLZ  1€YN=VNLS95()PVSVN`   *`U[OPH:OHYTH+LLW:LX\LUJPUN(WWYVHJOLZ[V7H[OVNLULZPZ  3.9 ZINF MEMBER ASSOCIATED WITH OTHER INSTITUTES 90  /LPKY\U4VSS0UMLJ[PVU0TT\UVSVN`   ;OVTHZ+HUKLRHY)PVPUMVYTH[PJZ   1VHJOPT4VYZJOOp\ZLY4`JVSVN`   4HYR\Z,UNZ[SLY4VSLJ\SHYHUK7O`ZPJHS7HYHZP[VSVN`  Knut Ohlsen - Gram-positive Cocci 40  LZ[LYTHUU/VZ[7H[OVNLU4PJYVIPV[H0U[LYHJ[PVUZ  Caroline Kisker - Structure-based Design 95  >PSTHAPLI\OY5VZVJVTPHS0UMLJ[PVUZI`:[HWO`SVJVJJP   4HYJV4L[aNLY/\THU+;PZZ\L4VKLSZ[V:[\K`/VZ[7H[OVNLU0U[LYHJ[PVUZPU0UMLJ[PV\Z9LZLHYJO   1 YNLU:LPILS*OLTPZ[Y`VM3P]PUN:`Z[LTZ   (\N\Z[:[PJO;YVWPJHS4LKPJPUL 3.2 INSTITUTE FOR HYGIENE AND MICROBIOLOGY 44  4H[[OPHZ-YVZJO4VSLJ\SHY:\Y]LPSSHUJLVM0U]HZP]L)HJ[LYPHS0UMLJ[PVUZ   6SP]LY2\YaHP4LKPJHS4PJYVIPVSVN`HUK4`JVSVN`   2SH\Z)YLOT/LSTPU[O0UMLJ[PVUZ  4. RESEARCH PROGRAMS  *OYPZ[VWO:JOVLU4VSLJ\SHY+PHNUVZ[PJZHUK-\UJ[PVUHS.LUVTPJZVM/\THU7H[OVNLUPJ)HJ[LYPH  +-.*VSSHIVYH[P]L9LZLHYJO*LU[LY*9*:-);YHUZYLNPV   (SL_HUKYH:JO\ILY[

4 5 4. RESEARCH PROGRAMS 4.18 ,\YVWLHU9LZLHYJO(YLH5L[^VYRZ,9(5L[  4.19 International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) 113 4.20 0)+3HIUL[*VVYKPUH[PVUVM(J[P]P[PLZMVY3HIVYH[VY`:\Y]LPSSHUJLVM0U]HZP]L)HJ[LYPHS+PZLHZLZ  4.21 >LSSJVTL;Y\Z[:[YH[LNPJ(^HYK  4.22 ,SZL2Y€ULY*LU[LYMVY(K]HUJLK4LKPJHS 4LKPJHS/\THUP[HYPHU:[\KPLZ> YaI\YN¶4^HUaH;HUaHUPH  4.23 )H]HYPHU9LZLHYJO5L[^VYRIH`YLZXUL[ 

5. INFRASTRUCTURE 5.1 593MVY4LUPUNVJVJJPHUK/HLTVWOPS\ZPUÅ\LUaHL  5.2 ;OL*VUZ\S[PUN3HIVYH[VY`MVY,JOPUVJVJJVZPZ  5.3 German Center for Infection Research (DZIF) 119 5.4 Interdisciplinary Center for Clinical Research (IZKF) 119 5.5 *VYL

6. TRAINING THE NEXT GENERATION 6.1 .YHK\H[L:JOVVSVM3PML:JPLUJLZ.:3:  6.2 +-.9LZLHYJO;YHPUPUN.YV\W.YHK\PLY[LURVSSLN.92+0UMLJ[  6.3 +-.9LZLHYJO;YHPUPUN.YV\W.YHK\PLY[LURVSSLN.92<)0  6.4 +-.9LZLHYJO;YHPUPUN.YV\W.YHK\PLY[LURVSSLN.92 :7/05.605-  

7. APPENDIX 7.1 A05-@V\UN0U]LZ[PNH[VY.YV\W3LHKLYZ(S\TUP  7. 2 4LL[PUNZHUK>VYRZOVWZJVVYNHUPaLKI`A05-4LTILYZ  7. 3 :LTPUHYZHUK*VSSVX\PH  7. 4 Funding 140 7. 5 7\ISPJH[PVUZ  7. 6 +PYLJ[VY`VM7LVWSL(ZZVJPH[LK^P[O[OLA05- 

6 7 1.1 GENERAL REMARKS

1 GENERAL REMARKS

8 9 *'*LI>:D>KLK>IHKM

genome architecture and its impact on antigenic variation JVUZVY[P\T1€YN=VNLS-YHUaPZRH-HILYHUK3HYZ)HYX\PZ[ *'*LI>:D>KLK>IHKM of trypanosomes, which was performed by his group in KL]LSVWUL^WYVNYHTTHISL95(IHZLKHU[PIPV[PJZHNHPUZ[ > YaI\YN ;OPZ Z[\K` HSZV PUJS\KLK [OL ÄYZ[ ZJ95(ZLX T\S[PYLZPZ[HU[WH[OVNLUZ(UH9P[H)YVJOHKVHUKT`ZLSM analysis of trypanosomes, which his lab set up jointly with [VNL[OLY ^P[O *OYPZ[PHU 4 SSLY 4\UPJO ^PSS LTWSV` OPNO 2018-2019 [OL:HSPIHNYV\W0U [OLNYV\WVM:LIHZ[PHU.LPILS throughput approaches to decipher stress pathways reported the cryo-electron microscopy resolution of the involved in antibiotics resistance and virulence of pathogens structure of the core complex of the type VII secretion in our StressRegNet consortium. Dear readers, system from mycobacteria in Nature. The success of the Besides the organization of several conferences A05-PZHSZVYLÅLJ[LKI`WYVMLZZVYZOPWVќLYZ[VJ\YYLU[A05- and symposia by ZINF members, we were happy to Infectious diseases remain one of the central challenges for VM [OL :(9:*V= 95( HUK [OL O\THU OVZ[ WYV[LVTL @0.SLHKLYZHUKI`[OLA05-@0.(S\TUPOVSKPUNUH[PVUHS welcome many international scientists and guest speakers ZJPLUJLHUKTLKPJPULPU[OLst century. The ongoing global (5H[\YL 4PJYVIPVSVN` PU WYLZZ >P[OPU [OL .92 + or international professorships or group leader positions. H[V\YJVSSVX\PHHUKZLTPUHYZLYPLZPU> YaI\YNW :(9:*V= WHUKLTPJ OHZ JSLHYS` ZOV^U [OH[ [OL ÄNO[ 0UMLJ[UL^WYVQLJ[ZVU:(9:*V=OH]LILLUSH\UJOLK 4VZ[YLJLU[S`^LJVUNYH[\SH[L:PUH)HY[MLSKVUHUVќLYMVY   ,HYSPLY PU  [OL -HJ\S[` VM )PVSVN` H^HYKLK HU against infectious diseases is of particular social, political, and, together with the lab of Chase Beisel, my group has a Full Professor (W3) position as well as Christian Pérez on honorary doctorate to the renowned infection biologist and and economic importance. The global challenges of a been developing a CRISPR/Cas-based diagnostic method OPZUL^WVZP[PVUHZ(ZZVJPH[L7YVMLZZVYH[<;/LHS[OHUK vaccinologist Rino Rappuoli (Siena). Peter Fineran from the rising threat of zoonotic pathogens such as coronaviruses [OH[ JHU KPZ[PUN\PZO KPќLYLU[ YLZWPYH[VY` ]PY\ZLZ PUJS\KPUN wish him a great start in Houston. LYULY.VLILSHUKJVSSLHN\LZHUKZ\WWVY[LK an internationally recognized and accredited institution. We HUKTPULPU >LSVVRMVY^HYK[VOVZ[PUNOPTHNHPUPU new technologies and innovative strategies to study I` [OL -LKLYHS 4PUPZ[Y` VM 9LZLHYJO HUK ;LJOUVSVN`HUK would like to express our deepest gratitude to the members [VJVU[PU\LV\YQVPU[^VYRVU[OLYLN\SH[PVUVM infection processes and develop novel therapeutics and afterwards the Bavarian Government, Würzburg gained VMV\Y:()HUK^LYLKLSPNO[LK[V^LSJVTL4LSHUPL)SVRLZJO bacterial CRISPR-Cas immune systems. vaccines. H JLU[YHS ZJPLU[PÄJ PUZ[P[\[PVU KLKPJH[LK [V JYVZZMHJ\S[` ,7-33H\ZHUULHUK1H`/PU[VU YaI\YN ;VKH[L 1€YN=VNLS1VPU[S`^P[O[OL0UZ[P[\[LVM4VSLJ\SHY0UMLJ[PVU Z[HY[!HUK^PZOOLYHSS[OLILZ[MVYOLYUL^YVSLPU WH[OVNLUZPUJS\KPUN]PY\ZLZ4VYLV]LY[OLPTWVY[HUJLVM the ZINF network comprises 50 principal investigators )PVSVN` 040) [OL A05- JLSLIYH[LK P[Z th birthday in leading the German Research Foundation. M\UKHTLU[HSYLZLHYJOPZOPNOSPNO[LKUV[SLHZ[I`[OL MYVT [OYLL MHJ\S[PLZ 4LKPJPUL )PVSVN` HUK *OLTPZ[Y`    [VNL[OLY ^P[O UH[PVUHS HUK PU[LYUH[PVUHS N\LZ[Z The past two years have been exceedingly rewarding Nobel Prize in Chemistry to Emmanuelle Charpentier and 7OHYTHJ`[OL/LSTOVS[a0UZ[P[\[LMVY95(IHZLK0UMLJ[PVU friends, and colleagues at an anniversary symposium and the achievements and research excellence of several Jennifer Doudna for the development of a novel CRISPR- 9LZLHYJO/090HUK[OL4H_7SHUJR9LZLHYJO.YV\WZVU W:WLHRLYZPUJS\KLK(SMYLK-VYJOLS7YLZPKLU[VM ZINF members were recognized by awards, honors, and Cas based genome editing method. Intriguingly, the Cas9 Systems Immunology. Research of ZINF members focuses 14<4HYPVU:JOpMLY)SHRL4HQVYLZZVM> YaI\YNA05- HWWVPU[TLU[ZPU  ;OLZLPUJS\KLT\S[PWSLOPNOS` ¸+5( ZJPZZVYZ¹ ^LYL PKLU[PÄLK PU [OL O\THU WH[OVNLU on molecular principles of host-pathogen interactions of ZJPLU[PÄJHK]PZVY`IVHYKTLTILYZ;VUL;¥UQ\T6ZSVHUK competitive and prestigious ERC (European Research :[YLW[VJVJJ\ZW`VNLULZ\UKLYZJVYPUN[OLYLX\PYLTLU[MVY diverse bacterial, fungal, eukaryotic, and viral pathogens, ,YPJ7HTLY*OPJHNVA05-(S\TU\Z+HUPLS3VWLa4HKYPK *V\UJPS .YHU[Z! HU (K]HUJLK .YHU[ [V ;OVTHZ 9\KLS continuous basic research on infectious diseases besides [OLOVZ[PTT\ULYLZWVUZL[OLYVSLVM95(PUPUMLJ[PVUZ 1€YN =VNLS +PYLJ[VY VM 040)/090 HUK 1€YN /HJRLY Consolidator Grants to Wolfgang Kastenmüller and Chase ÄUKPUNUV]LS^H`Z[V[YLH[[OLT;OLA05-WYV]PKLZHUPKLHS and the development of new infection models or anti- 7YLZPKLU[ VM [OL 5H[PVUHS (JHKLT` 3LVWVSKPUH ;OL Beisel, a Proof-Of-Concept Grant to Lars Dölken and network to join these tasks and I am looking forward to the infectives.  9VILY[2VJO.VSK4LKHS(^HYKLL:[HќHU5VYTHYR -SVYPHU,YOHYKHUKTVZ[YLJLU[S`H:[HY[PUN.YHU[[V next years of its infectious disease research activities. High-  ;VÄNO[ [OL :(9:*V= WHUKLTPJ YLZLHYJOLYZ HSS gave a Robert Koch Lecture and the current ZINF young 5L]H*HSPZRHU-\Y[OLYTVYL-YHUaPZRH-HILY @V\UN [OYV\NOW\[ HUK ZPUNSL JLSS ZLX\LUJPUN HZ ^LSS HZ UV]LS over the world, including many ZINF members, have pooled investigators presented their ongoing and future research. 0U]LZ[PNH[VY(^HYKHUK6SP]LY2\YaHP4HPU9LZLHYJO imaging technologies will provide new insights into complex their skills and resources to understand the epidemiology  (JLU[YHSJVTWVULU[VM[OLA05-OHZILLUP[Z`V\UN (^HYK YLJLP]LK H^HYKZ MYVT [OL .LYTHU :VJPL[` MVY host-pathogen interactions with unprecedented resolution. and pathobiology of this virus, develop a vaccine or novel investigator group (YIG) program, which was pioneering /`NPLUL HUK 4PJYVIPVSVN` +./4 A05- TLTILYZ (Y[PÄJPHSPU[LSSPNLUJLHWWYVHJOLZ^PSSWH]L[OL^H`[VHUHS`aL KPHNUVZ[PJZHUKHPK[OLWLVWSLZ\ќLYPUNMYVT*6=0+  in promotion of independent junior groups at German Hermann Einsele and Jörg Vogel were again listed by HUKPU[LYWYL[SHYNLKH[HZL[ZPU[OLÄNO[HNHPUZ[PUMLJ[PV\Z (Z[OL`HYLUV[JV]LYLKPU[OLYLWVY[WLYPVKZVTLL_HTWSLZ universities. The success of the ZINF YIG program has ;OVTZVU 9L\[LYZ HZ ¸/PNOS` *P[LK 9LZLHYJOLY¹ PU   diseases. of the ongoing Corona research activities in Würzburg are also contributed to the recruitment of additional young  0U   YaI\YN HUK [OL )H]HYPHU .V]LYUTLU[ MVY /VZWP[HS <2> 6SP]LY 2\YaHP HUK  PUP[PH[LK [OL )4)- -LKLYHS 4PUPZ[Y` VM ,K\JH[PVU OLHKVMHUL^A05-@0.VU95(IPVSVN`HUKWH[OVNLULZPZ ZINF members also initiated or participated in and Research)-funded Würzburg “Wü-KiTa-CoV” Corona of *SVZ[YPKPVPKLZ KPѝJPSL, expanding the range of studied PUUV]H[P]LZJPLU[PÄJUL[^VYRZVUPUMLJ[PV\ZKPZLHZLZW kindergarten study that investigates the still unclear extent WH[OVNLUZ PU > YaI\YN [V HUHLYVIPJ ZWLJPLZ (UK PU H 115). This includes, for example, the new DFG Research of viral spreading among young children. Several ZINF QVPU[]LU[\YL[OLA05-HUK[OL)PVJLU[LYYLJY\P[LK(UH9P[H YaI\YN > YaI\YN5V]LTILY a study in Cell employing single cell analyses to decipher @0.SLHKLYZ[VWLYMVYTOPNOPTWHJ[YLZLHYJOHZYLÅLJ[LK 4^HUaH;HUaHUPH¹ :L]LYHS A05- TLTILYZ HYL WHY[ KPќLYLUJLZPUZ`Z[LTPJPTT\ULYLZWVUZLZK\YPUNTPSKHUK I` ZL]LYHS ZLTPUHS WHWLYZ W\ISPZOLK PU    -VY of the recently established Bavarian research network ZL]LYL *6=0+  4H[OPHZ 4\UZJOH\LY 1€YN =VNLS HUK L_HTWSL A05- (S\TU\Z 5PJVSHP :PLNLS ZPUJL  34< IH`YLZXUL[ on “New strategies against multi-resistant colleagues have been charting a global interaction atlas 4\UPJOYLWVY[LKPUNature the global mapping of the 3D pathogens by means of digital networking”. In their 9IPV[PJZ

10 11 1.1 BERICHT DER SPRECHERIN

KPL 3LP[\UNLU ]VU  ]VU  KLYaLP[PNLU \UK  ]VU   1HOYL NLM€YKLY[ 4H[[OPHZ -YVZJO \UK 6SP]LY 2\YaHP BERICHT DER SPRECHERIN ehemaligen YIGs sind weiblich. PUP[PPLY[LUKHZÉ,SZL2Y€ULY-YLZLUP\Z*LU[LYMVY(K]HUJLK  +HZPU[LYKPZaPWSPUpYL YaI\YN KLU@0.ZOVJORHYp[PNL-VYZJO\UNa\IL[YLPILU^HZZPJO 4^HUaH;HUZHUPH¸4LOYLYL A05- 4P[NSPLKLY ZPUK ;LPSKLZ 2018-2019 PU TLOYLYLU    ]LY€ќLU[SPJO[LU IHOUIYLJOLUKLU neu gegründeten bayerischen Forschungsnetzwerks (YILP[LU^PKLYZWPLNLS[A\T)LPZWPLSW\ISPaPLY[LKPL.Y\WWL IH`YLZXUL[ zum Thema „Neue Strategien gegen KLZLOLTHSPNLUA05-(S\TU\Z5PJVSHP:PLNLSZLP[34< multiresistente Krankheitserreger mittels digitaler Liebe Leserinnen, liebe Leser, 4 UJOLUPUNaturePOYL(YILP[LUH\Z> YaI\YNa\YNSVIHSLU Vernetzung“. In ihrem 9IPV[PJZ-Konsortium entwickeln Kartierung der 3D Genomarchitektur von Trypanosomen 1€YN =VNLS -YHUaPZRH -HILY \UK 3HYZ )HYX\PZ[ UL\L 0UMLR[PVUZRYHUROLP[LU ZPUK H\JO PT  1HOYO\UKLY[ LPUL press(\JOPT9HOTLUKLZ.92+0UMLR[^\YKLU \UKKLYLU,PUÅ\ZZH\MKPL(U[PNLU]HYPH[PVUZV^PLKPLLYZ[L WYVNYHTTPLYIHYL 95(IHZPLY[L (U[PIPV[PRH (UH 9P[H der zentralen Herausforderungen in Wissenschaft und UL\L7YVQLR[La\:(9:*V=NLZ[HY[L[\UKKPL3HIVYL]VU ZJ95(ZLX (UHS`ZL KPLZLY 7H[OVNLUL 2VSSHIVYH[PVU TP[ Brochado und ich werden zusammen mit Christian 4LKPaPU0UZILZVUKLYLKPLHR[\LSSL:(9:*V=7HUKLTPL Chase Beisel und mir haben gemeinsam eine CRISPR/Cas- (. :HSPIH ,ILUMHSSZ PU Nature LYZJOPLULU  KPL (YILP[LU 4 SSLY 4 UJOLU PU \UZLYLT StressRegNet-Konsortium OH[ ]LYKL\[SPJO[ ^PL LZZLU[PLSS KPL )LRpTWM\UN ]VU IHZPLY[L +PHNUVZLTL[OVKL a\Y LYULY .VLILS \UK 2VSSLNLU   die aktuellen YIG Leiter/innen, sowie in den nationalen und ]VU A05- 4P[NSPLKLYU VYNHUPZPLY[ \UK ^PY K\YM[LU ]PLSL 9LZPZ[LUaLULYMVYKLY[LPULPU[LYKPZaPWSPUpYLA\ZHTTLUHYILP[ NLNY UKL[^\YKLKHZA05-a\UpJOZ[ÄUHUaPLSSK\YJOKHZ internationalen Professuren oder Gruppenleiterpositionen, internationale Wissenschaftler und Gastredner bei unseren von Wissenschaftlern, um neue Technologien und Bundesministerium für Forschung und Technologie und ^LSJOLKPLA05-(S\TUPPUULOHILU^PLKLY(SZQ UNZ[L 2VSSVX\PLU\UK:LTPUHYLUILNY LU: (UMHUN Strategien zur Erforschung von Infektionskrankheiten, ZWp[LYK\YJOKPL14<\UKKHZ)H`LYPZJOL:[HH[ZTPUPZ[LYP\T Beispiele möchten wir Sina Bartfeld zu einem Ruf auf ]LYSPLOKPL-HR\S[p[M Y)PVSVNPLKPL,OYLUKVR[VY^ YKL ZV^PLUL\L;OLYHWL\[PRH\UK0TWMZ[VќLa\LU[^PJRLSU gefördert. Damit erhielt Würzburg eine zentrale eine W3-Professur sowie Christian Pérez zu seiner neuen an den renommierten Infektionsbiologen und Vakkzinologen Dieser wissenschaftliche Bericht gibt einen Überblick ^PZZLUZJOHM[SPJOL,PUYPJO[\UNKPLZPJOMHR\S[p[Z ILYNYLPMLUK 7VZP[PVU HSZ (ZZVJPH[L 7YVMLZZVY HU KLY <;/LHS[O PU 9PUV9HWW\VSP:PLUH7YVMLZZVY7L[LY-PULYHU YaI\YN \U[LYKLYSHUNQpOYPNLU3LP[\UNKLYMY OLYLUA05-:WYLJOLY Der Erfolg und die Sichtbarkeit des ZINF KLY(SL_HUKLY]VU/\TIVSK[:[PM[\UN\T KHZ/090 PU  +HZA05-PZ[LPUPU[LYKPZaPWSPUpYLZ5L[a^LYR Jörg Hacker und Jörg Vogel zu einem international wurde wegweisend durch unseren internationalen 040)a\ILZ\JOLU\UKPUKLU3HIVYLU]VU*OHZL)LPZLS KHZ HR[\LSS  4P[NSPLKLY H\Z KYLP -HR\S[p[LU 4LKPaPU angesehenen Zentrum entwickelt hat. Gemeinsam mit wissenschaftlichen Beirat bestehend aus führenden und mir an der Regulation von bakteriellen CRISPR-Cas )PVSVNPL *OLTPL  7OHYTHaPL ZV^PL ]VT /LSTOVS[a KLT0UZ[P[\[M Y4VSLR\SHYL0UMLR[PVUZIPVSVNPL040)MLPLY[L Wissenschaftler/innen begleitet und unterstützt. Bei 0TT\UZ`Z[LTLUa\MVYZJOLU>PYMYL\LU\UZPOU 0UZ[P[\[M Y95(IHZPLY[L0UMLR[PVUZMVYZJO\UN/090\UKKLY KHZ A05-   ZLPULU  .LI\Y[Z[HN TP[ UH[PVUHSLU unseren Beiratsmitgliedern möchten wir uns ganz herzlich ^PLKLYILP\UZILNY LUa\K YMLU 4H_7SHUJR-VYZJO\UNZNY\WWL:`Z[LTPTT\UVSVNPLapOS[ \UK PU[LYUH[PVUHSLU .pZ[LU -YL\UKLU \UK 2VSSLNLU PT ILKHURLU\UK^PYMYL\LU\UZZLP[ 4LSHUPL)SVRLZJO  6I^VOS KPL :(9:*V= 7HUKLTPL KLYaLP[ PT +PL 4P[NSPLKLY MVYZJOLU HU TVSLR\SHYLU .Y\UKSHNLU ]VU 9HOTLU LPULZ 1\IPSp\TZZ`TWVZP\TZ :  A\ ,7-3 3H\ZHUUL \UK 1H` /PU[VU  YaI\YNLY ) YNLYTLPZ[LYPU 4HYPVU :JOpMLY wir der ehemaligen ZINF Nachwuchsgruppenleiterin und (\M[YL[LU ]VU HU[PIPV[PRHYLZPZ[LU[LU VKLY UL\HY[PNLU KLZ >PY[Z KLY 9VSSL ]VU 95( PU 0UMLR[PVULU ZV^PL KLY )SHRL KPL 4P[NSPLKLY KLZ ^PZZLUZJOHM[SPJOLU )LPYH[Z ;VUL Beiratsmitglied Katja Becker zu ihrer Wahl zur ersten Krankheitserregern eine enorme soziale und medizinische ,U[^PJRS\UNUL\LY0UMLR[PVUZTVKLSSLVKLY(U[PPUMLR[P]H ;¥UQ\T 6ZSV \UK ,YPJ 7HTLY *OPJHNV KLY LOLTHSPNL 7YpZPKLU[PU KLY +L\[ZJOLU -VYZJO\UNZNLTLPUZJOHM[ \UK Herausforderung. Die Bedeutung der Grundlagenforschung  0T 2HTWM NLNLU KPL :(9:*V= 7HUKLTPL KLT A05-5HJO^\JOZNY\WWLUSLP[LY +HUPLS 3VWLa 4HKYPK wünschen ihr alles Gute für ihre neue Rolle an der DFG- wird nicht zuletzt durch den kürzlich an Emmanuelle ZPJOaHOSYLPJOL4P[NSPLKLYKLZA05-HUNLZJOSVZZLUOHILU 1€YN =VNLS +PYLR[VY KLZ 040)/090 \UK 1€YN /HJRLY :WP[aLZLP[ *OHYWLU[PLY \UK 1LUUPMLY +V\KUH ]LYSPLOLULU  HYILP[LU -VYZJOLY ^LS[^LP[ KHYHU KPL (\ZIYLP[\UN \UK 7YpZPKLU[ KLY 5H[PVUHSLU (RHKLTPL 3LVWVSKPUH :[HќHU  (\JO    LYOPLS[LU TLOYLYL A05- 4P[NSPLKLY Chemie-Nobelpreis für die Entwicklung einer auf CRISPR- Pathogenese dieses Virus zu verstehen und einen neuen 5VYTHYR 7YLPZ[YpNLY KLY 9VILY[2VJO.VSKTLKHPSSL eine Reihe renommierter Preise und Ehrungen oder Cas basierten Genom-Editiermethode unterstrichen. Die 0TWMZ[Vќ +PHNUVZ[PRH VKLY ;OLYHWPLU a\ LU[^PJRLSU 0U  OPLS[KPL9VILY[2VJO=VYSLZ\UN\UKKPLKLYaLP[PNLU ^\YKLU H\M ^PJO[PNL 7VZP[PVULU LYUHUU[ +Ha\ apOSLU ,U[KLJR\UNKLY*HZ ¸+5(:JOLYL¸PT/\THUWH[OVNLU Würzburg hat z.B. das Institut für Virologie unter Leitung ZINF Nachwuchsgruppenleiter stellten ihre laufende und TLOYLYL WYLZ[PNL[YpJO[PNL ,9* ,\YVWLHU 9LZLHYJO :[YLW[VJVJJ\Z W`VNLULZ verdeutlicht, dass neben der ]VU 3HYZ +€SRLU ZLPUL 2HWHaP[p[LU M Y KPL :(9:*V= zukünftige Forschung vor. *V\UJPS.YHU[Z! ;OVTHZ 9\KLS LYOPLS[ LPULU (K]HUJLK translationalen Forschung die Grundlagenforschung +PHNUVZ[PRZ[HYRLY^LP[LY[\UK6SP]LY2\YaHP\UKLPU*VYVUH;LZ[aLU[Y\T @0. KHZ ^LN^LPZLUK M Y KPL -€YKLY\UN \UHIOpUNPNLY Proof-Of-Concept Grant, und jüngst erhielt Neva Caliskan -VYZJO\UNZUL[a^LYR \T ZPJO KPLZLU (\MNHILU a\ errichtet. Im Rahmen des InfectControl-Netzwerks initiierten 1\UPVYNY\WWLU HU KL\[ZJOLU YaI\YN NLOVS[ ^LYKLU RVUU[LU    RHTLU erneut von Thomson Reuters als „Highly Cited Researcher“ UL\L ,PUISPJRL TP[ UVJO UPL KHNL^LZLULY (\ŀZ\UN 2PUKLYU \U[LYZ\JO[ 4LOYLYL A05-4P[NSPLKLY ZPUK ;LPS zu den Gruppen von Sina Bartfeld (ZINF, Organoide als   NLSPZ[L[   LYOPLS[LU LNa\Y(UHS`ZL\UK0U[LYWYL[H[PVUNYVLY+H[LUZp[aLPT K\YJO KPL *OHYP[t )LYSPU KHZ ZPJO TP[ (Y[ \UK (\ZTH ,SP[LUL[a^LYR)H`LYU:[Y\R[\YIPVSVNPL]VU4`RVIHR[LYPLU -LSKILYN7YLPZ 4H[[OPHZ -YVZJO ^\YKL   a\T UL\LU Kampf gegen Infektionskrankheiten ebnen. KLY VYNHUZWLaPÄZJOLU 2YHUROLP[ZLU[Z[LO\UN LPULY zwei neue ZINF YIGs hinzu. Franziska Faber startete 7YpZPKLU[LU KLZ 4LKPaPUPZJOLU -HR\S[p[LU[HNLZ NL^pOS[  (IZJOSPLLUK T€JO[L PJO HSSLU A05- 4P[NSPLKLYU :(9:*V= 0UMLR[PVU ILMHZZ[ VKLY KLT IH`LYPZJOLU   POYL .Y\WWL a\Y 95()PVSVNPL \UK 7H[OVNLULZL \UK 1€YN =VNLS ^PYK PT 1HU\HY  KPL 7YpZPKLU[ZJOHM[ M Y KPL OLY]VYYHNLUKL A\ZHTTLUHYILP[ POYL )LP[YpNL a\ FOR-COVID Netzwerk (Co-Koordinator Jörg Vogel), das von *SVZ[YPKPVPKLZ KPѝJPSL, wodurch das Würzburger KLY,\YVWpPZJOLU(RHKLTPLM Y4PRYVIPVSVNPLHU[YL[LU KPLZLT)LYPJO[ZV^PLa\T,YMVSNKLZA05-KHURLU(\JO UL\L >LNL KLY 0UMLR[PVUZWYp]LU[PVU LU[^PJRLSU ZV^PL Forschungsrepertoire um anaerobe Spezies erweitert  A05-4P[NSPLKLY PUP[PPLY[LU VKLY ^PYR[LU a\KLT PU T€JO[LPJOKLY YaI\YN\UKKLT)H`LYPZJOLU die Entstehung und Entwicklung von COVID-19 besser wurde. Gemeinsam mit dem Biozentrum hat das ZINF innovativen Forschungsnetzwerken zu Infektionskrankheiten :[HH[ZTPUPZ[LYP\TM YPOYLRVU[PU\PLYSPJOL YaI\YNNL^PUULUR€UULU TP[ :  +Ha\ NLO€YLU ILPZWPLSZ^LPZL KPL UL\L ZINF danken. aus Berlin und Bonn publizierten vor kurzem eine Studie 0OY 3HIVY \U[LYZ\JO[ KPL :`Z[LTIPVSVNPL ]VU (U[PIPV[PRH +-. -VYZJO\UNZNY\WWL   É(K]HUJLK JVUJLW[Z PU in CellPUKLYZPLTP[[LSZ,PUaLSaLSSHUHS`ZLU YaI\YN5V]LTILY

12 13 1.2 STRUCTURE OF THE ZINF

1.2 STRUCTURE OF THE ZINF

2018-2019 EXECUTIVE COMMITTEE MEMBERS

CYNTHIA SHARMA WOLFGANG KASTENMÜLLER ;OLA05-JVUZPZ[ZVMÄ]LPU[LYUHSHUKUPULHZZVJPH[LKPUZ[P[\[PVUZZWYLHKHJYVZZ[OL-HJ\S[`VM4LKPJPULPUJS\KPUN[OL :WVRLZWLYZVUZPUJL  Institute for Virology and Immunobiology

LARS DÖLKEN OLIVER KURZAI Institute for Virology and Immunobiology 0UZ[P[\[LMVY/`NPLULHUK4PJYVIPVSVN` Chair of Virology *OHPYVM4LKPJHS4PJYVIPVSVN` 4`JVSVN`

HERMANN EINSELE THOMAS RUDEL +LWHY[TLU[VM0U[LYUHS4LKPJPUL00A04 +LWHY[TLU[VM4PJYVIPVSVN`)PVJLU[LY *OHPYVM0U[LYUHS4LKPJPUL00 *OHPYVM4PJYVIPVSVN`

MATTHIAS FROSCH JÖRG VOGEL 0UZ[P[\[LMVY/`NPLULHUK4PJYVIPVSVN` 0UZ[P[\[LVM4VSLJ\SHY0UMLJ[PVU)PVSVN` *OHPYVM/`NPLULHUK4PJYVIPVSVN` *OHPYVM4VSLJ\SHY0UMLJ[PVU)PVSVN`0

SCIENTIFIC ADVISORY BOARD MEMBERS

MICHAEL GILMORE DAVID HOLDEN *OHPYVM[OL:()ZPUJL ZPUJL )VZ[VU<: London, GB

KATJA BECKER ERIC PAMER   ZPUJL Bonn, DE *OPJHNV<:

MELANIE BLOKESCH GISELA STORZ ZPUJL  ZPUJL Lausanne, CH )L[OLZKH<:

JAY HINTON TONE TØNJUM ZPUJL  ZPUJL Liverpool, GB Oslo, NO

14 15 1.3 EVENTS SURROUNDING THE ZINF

1.3 EVENTS SURROUNDING THE ZINF

CELEBRATING A QUARTER CENTURY OF THE ZINF

NOVEMBER 14TH, 2018

+LUUPZ2VWLJRVHUK;VIPHZkSZJOSpNLY 0U [VNL[OLY^P[O[OL0UZ[P[\[LVM4VSLJ\SHY0UMLJ[PVU)PVSVN`040)[OL9LZLHYJO*LU[LYMVY0UMLJ[PV\Z+PZLHZLZA05- JLSLIYH[LK P[Z th HUUP]LYZHY`;OL JLSLIYH[PVUZ PUJS\KLK H VULKH` ZJPLU[PÄJ Z`TWVZP\T [OH[ HSSV^LK MVY L_JOHUNLZ IL[^LLUJ\YYLU[HUKMVYTLYA05-TLTILYZA05-ZJPLU[PÄJHK]PZVY`IVHYKTLTILYZMYPLUKZJVSSLHN\LZHUKHS\TUPVM the Young Investigator Program.

>P[O[OLLZ[HISPZOTLU[VM[OLA05-PU I`7YVMLZZVYZ=VSRLY[LY4L\SLU>LYULY.VLILS1€YN/HJRLYHUKJVSSLHN\LZ > YaI\YN NHPULK H JLU[YHS JYVZZMHJ\S[` ZJPLU[PÄJ PUZ[P[\[PVU KLKPJH[LK [V [OL PU[LYKPZJPWSPUHY` YLZLHYJO VM PUMLJ[PV\Z KPZLHZLZ`LHYZHM[LYP[ZMV\UKH[PVU[OLA05-JV\U[ZWYPUJPWHSPU]LZ[PNH[VYZHZTLTILYZ

;OLHUUP]LYZHY`Z`TWVZP\T^HZHUVWWVY[\UP[`[VYLÅLJ[\WVU[OLHJJVTWSPZOTLU[ZVM[OLA05-NL[[VRUV^[OLYLZLHYJO VM[OLJ\YYLU[Ä]L`V\UNPU]LZ[PNH[VYNYV\WSLHKLYZHUKKPZJ\ZZ[OLM\[\YLVMTVSLJ\SHYPUMLJ[PVUIPVSVN`YLZLHYJOH[IV[O [OL14<> YaI\YNHUK[OLPU[LYUH[PVUHSYLZLHYJOJVTT\UP[`;OLWHY[PJPWHU[ZLUQV`LK[OL9VILY[2VJO3LJ[\YLNP]LUI` [OL 9VILY[2VJO.VSK4LKHS(^HYKLL7YVMLZZVY:[HќHU5VYTHYRHZ^LSSHZNYLL[PUNZHUKZJPLU[PÄJWYLZLU[H[PVUZ by national and international guests. In addition, Dr. Dennis Kopecko and Prof. Dirk Haller gave farewell lectures in honor VM+Y;VIPHZkSZJOSpNLYºZYL[PYLTLU[MYVT[OL040)

ZINF IMIB 25TH ANNIVERSARY 2SH\Z;V`RH>LYULY.VLILSHUK4HY[PU9€SSPUNKRIISLM[[VYPNO[

Former and current speakers of the ZINF (left to right: Jörg Hacker, Jörg Vogel, and Cynthia Sharma).

+HUPLS3VWLa*`U[OPH:OHYTH;VUL;¥UQ\T4HYPVU:JOpMLY)SHRL1€YN=VNLS(SMYLK-VYJOLSHUK Jörg Hacker (left to right).

16 17 1.3 EVENTS SURROUNDING THE ZINF

3D TISSUE INFECTION SYMPOSIUM CEREMONY TO THE 80TH BIRTHDAY OF WERNER GOEBEL

APRIL 5TH - 7TH, 2019 OCTOBER 3RD, 2019

The 3D Tissue Infection Symposium provided a platform to bring together early stage researchers as well as experienced *VSSLHN\LZHUKMYPLUKZJLSLIYH[LK[OL thIPY[OKH`VM7YVMLZZVY>LYULY.VLILSHWPVULLYPU[OLÄLSKVMTLKPJHSTPJYVIPVSVN` scientists from academia and pharmaceutical industry working on 3D human tissue cultures. The three-day symposium HUKHJVMV\UKLYVM[OLA05-(Z[OLÄYZ[*OHPYVM4PJYVIPVSVN`H[[OL YaI\YNOL^HZHTVUN[OLRL`ZJPLU[PZ[Z included talks by distinguished national and international speakers as well as talks and poster presentations by the graduate [OH[PUP[PHSS`PKLU[PÄLKKPZLHZLJH\ZPUNMHJ[VYZPUIHJ[LYPH7YVMLZZVY.VLILSPZHSZVHWHZZPVUH[LHUKKPZ[PUN\PZOLKWPHUPZ[^OV Z[\KLU[ZVM[OL.92+0UMLJ[(SSWHY[PJPWHU[ZLUQV`LK[OLSP]LS`ZJPLU[PÄJKPZJ\ZZPVUZHIV\[[OLHK]HU[HNLZVM\ZPUN VM[LUWLYMVYTLZH[JLYLTVUPHSHJ[ZH[[OL YaI\YN complex 3D human tissue models to study host-pathogen interactions.

HONORARY DOCTORATE FOR RINO RAPPUOLI

;OL+;PZZ\L0UMLJ[PVU:`TWVZP\T^HZVYNHUPaLKI`[OL7O+Z[\KLU[ZVM[OL+-.M\UKLK.920THNLZ!+H]PK2LZZPLHUK4V[HOHYLOZHKH[/L`KHYPHU JANUARY 31ST, 2020

Professor Rino Rappouli from Siena (Italy) is one of the most renowned researchers in infection biology and development of ]HJJPULZ^VYSK^PKL;VWH`[YPI\[L[VOPZL_[YHVYKPUHY`ZJPLU[PÄJHJOPL]LTLU[ZOL^HZH^HYKLKHU/VUVYHY`+VJ[VYH[LKLNYLL I`[OL-HJ\S[`VM)PVSVN`H[[OL YaI\YNPUHJLYLTVUPHSHJ[

President of the Leopoldina Jörg Hacker, Roy Gross, Dean of Biology Charlotte Förster, Honorary +VJ[VY(^HYKLL9PUV9HWWV\SP

18 19 SINA BARTFELD - ZINF

2 ANA RITA BROCHADO - ZINF/BIOCENTER ZINF YOUNG INVESTIGATORS FRANZISKA FABER - ZINF

SEBASTIAN GEIBEL - ELITE NETWORK BAVARIA

J. CHRISTIAN PÉREZ - ZINF/IZKF 2 ZINF YOUNG INVESTIGATORS

ORGANOIDS AS HOST MODELS

DR. SINA BARTFELD Research Center for Infectious Diseases [email protected] I +49 931 31 80121 www.imib-wuerzburg.de

RESEARCH INTERESTS opened new avenues for medical SELECTED PUBLICATIONS research: a culture system has been Kayisoglu O, Weiss F, Niklas C, The group studies host-pathogen developed that allows theoretically Pierotti I, Pompaiah M, Wallaschek N, interactions in the gastrointestinal endless culture of primary cells from Germer CT, Wiegering A, Bartfeld S tract using human stem cell-derived virtually any patient. In this approach, (2020) 3VJH[PVUZWLJPÄJ JLSS PKLU[P[` organoids as host models. We are epithelial stem cells are isolated from rather than exposure to GI microbiota KLÄULZTHU`PUUH[LPTT\ULZPNUHSSPUN particularly interested in the innate the respective organ, placed in an JHZJHKLZPU[OLN\[LWP[OLSP\T immune response and gastric extracellular matrix and supplemented Gut gutjnl-2019-319919 pathogens, such as Helicobacter ^P[O HU VYNHUZWLJPÄJ JVJR[HPS VM (Epub ahead of print) pylori and Epstein Barr Virus, and their growth factors and inhibitors. The Stanifer ML, Muenchau S, Pervolaraki contribution to gastric carcinogenesis. stem cells subsequently divide and K, Kanaya T, Mukenhirn M, Albrecht grow into three-dimensional mini- D, Odendall C, Kagan J, Bartfeld S, The gastrointestinal tract is lined by a versions of the organ, from which they Figure 2: Human gastric organoids generated from healthy tissue (left) or cancer tissue (right). Ohno H, Boulant S (2020) Asymmetric single-layered epithelium that renews have been generated, and are thus Image by Nina Wallaschek. KPZ[YPI\[PVUVM;39SLHKZ[VHWVSHYPaLK immune response in human intestinal P[ZLSM L]LY` Ä]L KH`Z ;OL Z[LT JLSSZ called “organoids”. Organoids have epithelial cells. required for this constant regeneration been grown from the human small Nature Microbiology 5(1):181-191 reside in the epithelium itself, intestine, colon, stomach, and many cellular identity also extends to the translocation, indicating that CagA for cancer development. This will IL[^LLU [OL KPќLYLU[PH[LK JLSSZ ;OL other organs. For infection biology, innate immune signaling cascades of translocation and HBP delivery into hopefully help to delineate the steps Wallaschek N, Niklas C, Pompaiah M, Wiegering A, Germer CT, Kricher S, pathways that govern gastric stem organoids are a very promising new the epithelial cells: gastric cells express host cells are distinct features of the in infection-associated carcinogenesis Brändlein S, Maurus K, Rosenwald A, JLSS PKLU[P[` HUK KPќLYLU[PH[PVU ULLK TVKLS Z`Z[LT ILJH\ZL MVY [OL ÄYZ[ ]LY`ZWLJPÄJHUKV[OLYPUUH[LPTT\UL infection. and eventually provide new strategies Yan HHN, Leung SY, Bartfeld S (2019) to be tightly controlled, because if [PTL[OLLќLJ[VMPUMLJ[PVUVUWYPTHY` receptors than small intestinal cells or for therapies. ,Z[HISPZOPUN W\YL JHUJLY VYNHUVPK the delicate balance guarding healthy cells, including stem cells, can be cells of the colon. This organization of Organoids cannot only be grown from J\S[\YLZ! PKLU[PÄJH[PVU ZLSLJ[PVU HUK ]LYPÄJH[PVU VM JHUJLY WOLUV[`WLZ HUK homeostasis is disturbed, cancer can studied. the innate immune sensors along the healthy tissue, but also from cancer NLUV[`WLZ arise. In the stomach, infections by cephalocaudal axis is at least in part tissue. The analysis of paired organoids Journal of Molecular Biology 431(15): pathogens, such as the carcinogenic developmentally programmed in the from healthy and tumor tissue from 2884-2893 bacterium H. pylori, and the resulting HIGHLIGHTS & OUTLOOK stem cells, independent of contact to the same patient has demonstrated PUÅHTTH[PVU WSH` H JLU[YHS YVSL PU [OLNHZ[YVPU[LZ[PUHSÅVYH [OH[ [OL WH[PLU[ZWLJPÄJ VYNHUVPK»Z Bartfeld S (2016) 4VKLSPUN PUMLJ[PV\Z KPZLHZLZ HUK OVZ[TPJYVIL PU[LYHJ[PVUZ cancer development. We aim to further establish organoids drug response can be associated with PUNHZ[YVPU[LZ[PUHSVYNHUVPKZ as a standard in-vitro model for For infection, we use microinjection of its mutational status. This supports Developmental Biology 420(2):262–27 In the past decade, advances in infection research. Human gastro- bacteria into the organoids or infection the conclusion that organoids not [OL ÄLSK VM Z[LT JLSS IPVSVN` OH]L intestinal organoids self-organize into of two-dimensional layers of cells grown only faithfully represent the healthy 3D cystic structures with a central from organoids. When organoids are epithelium, but also recapitulate the S\TLU ÅHURLK I` H ZPUNSLSH`LYLK infected with H. pylori, lineages of the hallmarks of disease and are useful polarized epithelium, therefore they NSHUKZ TV\U[ H Z[YVUN PUÅHTTH[VY` models for drug development and closely resemble the in-vivo situation. response, while lineages of the pit testing. Each organoid harbors stem cells as react only marginally. Currently, it is ^LSSHZKPќLYLU[PH[LKJLSSZUL_[[VLHJO \UJSLHY^O`ZWLJPÄJJLSS[`WLZTV\U[ We will continue to combine V[OLY PKLHSS` VYNHUPaLK PU ZWLJPÄJ H KPќLYLU[ YLZWVUZL [V [OL PUMLJ[PVU organoid technology with system- domains within one organoid, such In cell lines and 2D layers of cells wide approaches such as RNA-seq as an intestinal villus-like domain and grown from organoids, the bacterium and targeted approaches such as an intestinal crypt-like domain. The employs its type IV secretion system CRISPR-Cas-mediated knockout to tissue identity is conserved in the to inject not only the bacterial protein better understand host-pathogen adult stem cells: organoids generated CagA, but also a bacterial sugar, interactions. We expect that this from gastric tissue harbor gastric D-NS`JLYVу+manno-heptose-1,7- will provide new insights into the cell lineages (such as gland mucous IPZWOVZWOH[Lу/)7;OPZJHU[YPNNLY pathogenic changes in the host cells and pit mucous cells) and the innate immune response in the cell induced by infection. Also, as organoids generated from intestinal host cell. An RNAi based genome- organoids can be established from tissue harbor intestinal cell lineages ^PKLZJYLLUOHZPKLU[PÄLK(372HUK virtually any patient, a comparison of (such as enterocytes and goblet TIFA as crucial signaling components host reactions from a broad range of cells). Analyzing a new biobank of PU]VS]LK PU [OPZ HJ[P]H[PVU 5-ы) patient-derived organoids will enable Figure 1: 3D human organoids. Red: Occludin. Blue: Nuclei. 42 organoids of the gastrointestinal activation through the ALPK1-TIFA- [OL PKLU[PÄJH[PVU VM WH[PLU[ZWLJPÄJ Image by Carolin Niklas. tract, we recently found that this axis is independent on CagA protein responses and possible risk factors

22 23 2 ZINF YOUNG INVESTIGATORS

SYSTEMS BIOLOGY OF ANTIBIOTIC ACTION

DR. ANA RITA BROCHADO Emmy Noether group leader, Research Center for Infectious Diseases Department of Microbiology, Theodor Boveri Institute, Biocenter [email protected] I +49 931 31 88860 www.brochadolab.com

RESEARCH INTERESTS nation therapies, and imposes an SELECTED PUBLICATIONS exhaustive and laborious testing. Domenech A, Brochado AR, Sender V, The discovery of antibiotics during the Hentrich K, Henriques-Normark B, ÄYZ[ OHSM VM [OL th century enabled Our group investigates molecular Typas A and Veening JW (2020) Proton LѝJPLU[ JVU[YVS VM V[OLY^PZL KLHKS` mechanisms of drug combinations Motive Force Disruptors Block Bacterial bacterial infections. Since then, several across pathogenic Gram-negative *VTWL[LUJL HUK /VYPaVU[HS .LUL ;YHUZMLY antibiotic classes targeting essential bacteria. We focus on the Cell Host & Microbe 27(4):544-555 processes in bacteria made it to Enterobacteriaceae model organisms highly successful clinical applications. Escherichia coli and Salmonella Brochado AR, Telzerow A, Bobonis J, Nonetheless, rapid development enterica serovar Typhimurium, as Banzhaf M, Mateus A, Selkrig J, Huth E, Bassler S, Zamarreño Beas J, and widespread antibiotic resistance well as on the priority pathogen Zietek M, Ng N, Foerster S, Ezraty B, seriously compromises antibiotic 7HLY\NPUVZH. We develop novel high- Py B, Barras F, Savitski MM, Bork P, LќLJ[P]LULZZHUKWHUYLZPZ[HU[Z[YHPUZ throughput approaches, and apply Figure 2: Drug interactions in bacteria: (a) drug interaction network in E. coliHUKIZWLJPLZZWLJPÄJP[`VMKY\NPU[LYHJ[PVUZ Göttig S and Typas A (2018) Species- that resist all available antibiotics them in tandem with reverse Image from Brochado et al., 2018, Nature. ZWLJPÄJ HJ[P]P[` VM HU[PIHJ[LYPHS KY\N combinations. have been reported in the last few and computational biology tools to Nature 559(7713):259-263 years. Following recent reports by the derive general principles driving drug World Health Organization (WHO), interactions in bacteria. ZWLJPLZZWLJPÄJP[`IYPUNZHJYVZZKY\N JVTIPUH[PVUZ [OL LќLJ[P]L PU[YH is on deepening our understanding Maier L, Pruteanu M, Kuhn M, Zeller G, Gram-negative bacteria including combinations as prime candidates for cellular antibiotic concentration of the of antibiotic Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, Patil KR, numerous Enterobacteriaceae and narrow-spectrum treatments, where decreases upon addition of a second combinations leading to cell death, Bork P, Typas A (2018) Extensive impact 7ZL\KVTVUHZ HLY\NPUVZH are of HIGHLIGHTS & OUTLOOK the pathogen is primarily targeted compound. Perhaps this is not totally and large-scale drug combination VM UVUHU[PIPV[PJ KY\NZ VU O\THU N\[ special concern, due to the naturally and commensals are spared. Which unexpected for Gram-negatives, and assays are excellent tools to probe bacteria. low permeability of their cell envelope. ,ѝJPLU[ Z`ULYNPZ[PJ JVTIPUH[PVUZ mechanisms explain the observed it clearly suggests that drug transport such complex cellular responses. Nature 555(7698):623-628 have been shown to counteract ZWLJPLZZWLJPÄJP[` PZ JVTWSL[LS` could strongly drive the outcome of We already started establishing high- Synergistic antibiotic combinations resistance mechanisms and to bypass unexplored to date, and is thereby a drug combinations. There are several throughput methods to test how drug AWARDS VќLY HU HS[LYUH[P]L Z[YH[LN` MVY membrane permeability limitations in central topic of the Emmy Noether mechanisms involving classical stress combinations impact bacterial cell DFG Emmy Noether Fellowship for junior overcoming the current lack of Gram-negatives. Drug combinations project that we just started in the response pathways that bacteria death in Gram-negative pathogens. group leaders on the topic: +LJPWOLYPUN LќLJ[P]LHU[PIPV[PJZPU[OLZOVY[[LYT are synergistic if the combined lab. We apply comparative reverse can employ to enable such cross- This study will reveal general principles TVSLJ\SHYTLJOHUPZTZVMIHJ[LYPHSJLSS However, the molecular mechanisms PUOPIP[PVU LќLJ[ PZ Z[YVUNLY [OHU [OL genetics approaches using mutant protection, namely activation of major of cell death-based synergy and KLH[O HUK WLYZPZ[LUJL \ZPUN HU[PIPV[PJ underlying drug combinations are expected additivity, and antagonistic SPIYHYPLZ VM KPќLYLU[ WH[OVNLUZ [V Lў\_ W\TWZ Z\JO HZ (JY();VS* antagonism, and how they hold combination (2019-2025) largely unknown, which impairs if it is weaker. In a close analogy to tackle this question. We focus on However, the regulatory triggers for HJYVZZKPќLYLU[IHJ[LYPH rational design of antimicrobial combi- genetic interactions (or epistasis), deciphering molecular mechanisms such responses are widely unknown, synergy and antagonism are generally of synergistic combinations especially especially in the context of drug referred to as “drug interactions” and WV[LU[ HNHPUZ[ KPѝJ\S[[V[YLH[ combinations. This topic bridges YLÅLJ[M\UJ[PVUHSPU[LYHJ[PVUZIL[^LLU pathogens, such as 7HLY\NPUVZH ongoing and upcoming projects in the cellular processes triggered by the Preliminary results point to multi- our lab in a future collaboration with individual . This renders drug factorial mechanisms, not only Prof. Dr. Cynthia Sharma (IMIB). In combinations a prime tool to probe involving the antibiotic target, but particular, we plan to deploy unique molecular mechanism and cellular also other far less intuitive cellular high-throughput technology to complexity, in addition to their explicit processes. Progressing molecular decipher key regulatory responses clinical potential. work will further elucidate the JVU[YVSSPUN KY\N HJ[P]P[` PU KPќLYLU[ mechanism of synergy and provide pathogens. 0UHWPVULLYZ[\K`0WYVÄSLK% a breakthrough towards designing drug interactions across three Gram- ZWLJPLZZWLJPÄJ[YLH[TLU[Z Evidence of complex drug action negative species, including prominent in bacteria is greatly increasing, pathogens. One of the most striking An intriguing feature of drug especially considering drug action ÄUKPUNZMYVT[OPZZ[\K`PZ[OH[Z`ULYN` interactions is a high prevalence of towards bacterial cell death. and antagonism are incredibly antagonism over synergy – meaning Nowadays it is widely acknowledged ZWLJPLZZWLJPÄJ L]LU HJYVZZ JSVZLS` that bacterial cells can more often that cell death by antibiotics likely related species. On one hand this is a LќLJ[P]LS` THRL \ZL VM VUL KY\N [V results from multiple factors. Yet, surprising observation, since antibiotic undermine the other rather than the investigating such factors in detail Figure 1: Synergistic drug combinations to overcome antibiotic resistance. targets are typically conserved across opposite. We have previously shown remains very challenging. A major Image from Brochado et al., 2018, Nature. bacteria. On the other hand, their that, for at least 50% of antagonistic focus of my Emmy Noether project

24 25 2 ZINF YOUNG INVESTIGATORS

RNA BIOLOGY OF CLOSTRIDIOIDES DIFFICILE

DR. FRANZISKA FABER Research Center for Infectious Diseases [email protected] I +49 931 31 86280 www.imib-wuerzburg.de

RESEARCH INTERESTS to other enteric pathogens such as SELECTED PUBLICATIONS Salmonella. In addition, *KPѝJPSL Fuchs M, Lamm-Schmidt V, Ponath F, My research group is taking an is thus far the only Gram-positive Jenniches L, Barquist L, Vogel J, Faber RNA-centric approach to address species in which the RNA chaperone F (2020) (U 95(JLU[YPJ NSVIHS ]PL^ riboregulation of gene expression Hfq has a large impact on gene VM *SVZ[YPKPVPKLZ KPѝJPSL YL]LHSZ IYVHK in *SVZ[YPKPVPKLZ KPѝJPSL as well expression and bacterial HJ[P]P[` VM /MX PU H JSPUPJHSS` PTWVY[HU[ Gram-positive bacterium. as the clinical need for narrow- such as sporulation, which is a crucial bioRxiv doi: 10.1101/2020.08.10. spectrum antibiotics for the treatment pathogenic feature of this bacterium 244764 of infections with *KPѝJPSL. We enabling transmission between hosts. Faber F, Thiennimitr P, Spiga L, aim to understand the molecular Byndloss MX, Litvak Y, Lawhon S, underpinnings of virulence regulation Andrews-Polymenis HL, Winter SE, in *KPѝJPSL with a strong focus on HIGHLIGHTS & OUTLOOK Bäumler AJ (2017) 9LZWPYH[PVUVMTPJYV small regulatory RNAs (sRNAs) and IPV[HKLYP]LK WYVWHULKPVS KYP]LZ Figure 2: The impact of antibiotic-induced disruption of the microbiota on *KPѝJPSL gut colonization and pathogenesis. :HSTVULSSHL_WHUZPVUK\YPUNJVSP[PZ will leverage this knowledge for the We are identifying sRNA candidates PLoS Pathogens 13(1):e1006129 KL]LSVWTLU[ VM ZWLJPLZZWLJPÄJ as well as cognate RNA-binding RNA-based therapeutics directed proteins (RBPs) to characterize their Faber F, Tran L, Byndloss MX, against *KPѝJPSL. role in gene regulation with a focus Infections with *KPѝJPSL are inherently bacteria and computationally predict infections in the presence of selected Lopez CA, Velazquez EM, Kerrinnes T, Nuccio SP, Wangdi T, Fiehn O, on virulence pathways. To date, only KPѝJ\S[ [V [YLH[ ^P[O JVU]LU[PVUHS optimal target sequences through members of the microbiota that Tsolis RM, Bäumler AJ (2016) Host- *KPѝJPSL is currently the leading cause one RBP, Hfq, has been shown to be broad-spectrum antibiotics because machine learning approaches. were shown to impact *KPѝJPSL gut TLKPH[LK Z\NHY V_PKH[PVU WYVTV[LZ of antibiotic-associated diarrhea, as functional and not a single sRNA has accompanying disruption of the colonization. Through combination WVZ[HU[PIPV[PJWH[OVNLUL_WHUZPVU infection with *KPѝJPSL results in been mechanistically characterized microbiota generates an environment To investigate regulatory mechanisms of dual RNA-seq and bacteriological Nature 534(7609):697-699 :LSLJ[LK MVY 5H[\YL 4PSLZ[VULZ PU [OL asymptomatic colonization in healthy in *KPѝJPSL. Utilizing state of the art that is permissive for *KPѝJPSL governing host-pathogen interactions and immunohistological methods, /\THU4PJYVIPV[H9LZLHYJO individuals but can lead to widespread methods of bacterial RNA biology, growth. This poses an urgent need for during infection with *KPѝJPSL, we these studies will provide insights into and potentially lethal pathologies after we have generated high-resolution treatment strategies that are narrow- aim to employ advanced cell culture the relevant cellular host processes antibiotic treatment. Previous research 95( THWZ [V KLÄUL [YHUZJYPW[VTL ZWLJ[Y\T VY H[ ILZ[ ZWLJPÄJHSS` models to recreate the human targeted by the pathogen or the AWARDS has strongly focused on transcriptional architecture and build a global targeting *KPѝJPSL. RNA-based anti- large intestine, a mostly anaerobic bacterial niche co-inhabitants. Young Investigator Prize (Förderpreis) regulation of *KPѝJPSL sporulation, atlas of transcriptional and post- microbials, including peptide nucleic environment in which *KPѝJPSL can of the German Society for Hygiene and toxin production, and central energy transcriptional control in *KPѝJPSL. acids (PNAs), are an attractive tech- thrive. Using a polarized Transwell Microbiology, DGHM (2018) metabolism. However, the role of Combined with Hfq pull-down UVSVN`MVYZWLJPLZZWLJPÄJHU[PIPV[PJZ model of colonic cells under micro- riboregulation during *KPѝJPSL infec- approaches, this has revealed a broad because they inhibit essential aerobic conditions, we can perform tion is less well understood compared RNA-binding activity for Hfq and led to genes on the RNA level through PU]P[YV *KPѝJPSL infections over [OLPKLU[PÄJH[PVUVMWV[LU[PHSYLN\SH[LK ZLX\LUJLZWLJPÄJ IPUKPUN [V [OL a course of 48 hours allowing the target genes involved in sporulation. targeted mRNA. Proof-of-concept concomitant assessment of bacterial Moreover, to identify functional RNA- for this approach has already been growth, toxin production, and protein complexes, we have applied demonstrated in Gram-negative (LN sporulation, as well as associated host Grad-seq to predict complexes of Escherichia coli, Salmonella enterica) responses in a time-resolved manner. RNA and protein in *KPѝJPSL. Our and Gram-positive (LN Listeria We will apply this model to compare work on *KPѝJPSL establishes a rich TVUVJ`[VNLULZ) species. Mechanistic OVZ[WH[OVNLUPU[LYHJ[PVUZVMKPќLYLU[ resource for researchers interested in insights from our studies on RNA- clinical strains with varying pathogenic this species, but also for bacterial RNA based gene regulation will inform the potential. Further, in collaboration biology in general as the obtained in- design strategies for PNA candidates. with the research group of Alexander gradient distributions provide also 0UP[PHS ^VYR PU V\Y SHI OHZ PKLU[PÄLK Westermann (HIRI) and Marco Metzger evidence for novel types of Hfq-RNA a peptide-PNA candidate targeting (Tissue Engineering and Regenerative interactions. In addition, we have the essential gene rpoB that inhibits Medicine, University Hospital and PKLU[PÄLKHUV]LS95(IPUKPUNWYV[LPU *KPѝJPSL growth and establishes Fraunhofer IGB, Würzburg), we are with global RNA-binding activity in proof-of-concept for this approach. To currently establishing a host model *KPѝJPSL Current and future projects PKLU[PM`LќLJ[P]LHUKZWLJPLZZWLJPÄJ based on human primary cells that will investigate the implications of PNA targets mediating bacterial aims to recapitulate the in-vivo RNA-based regulation for *KPѝJPSL inhibition, we are collaborating with situation. This includes an anaerobic virulence. Lars Barquist (HIRI) and Jörg Vogel TPSPL\ + Z[Y\J[\YLZ YLÅLJ[PUN Figure 1: Confocal microscopy image showing *SVZ[YPKPVPKLZ KPѝJPSL 630 expressing mCherryOPT 040)/090 [V PU]LZ[PNH[L [OL LќLJ[Z colonic crypts, and a mucus layer. (Ransom et al., 2015) under the control of the cwp2 promoter. Image by Franziska Faber. of PNAs on multiple pathogenic In the long term, we will investigate

26 27 2 ZINF YOUNG INVESTIGATORS

STRUCTURAL BIOLOGY OF MYCOBACTERIA

DR. SEBASTIAN GEIBEL Research Center for Infectious Diseases Elite Network Bavaria [email protected] I +49 931 31 84590 www.imib-wuerzburg.de

RESEARCH INTERESTS In M. tuberculosis, three homologous SELECTED PUBLICATIONS T7SSs (ESX-1, ESX-3, ESX-5) play Mietrach N, Damián-Aparicio D, Pathogenic bacteria such as central roles in its immune evasion Mielich-Süss B, Lopez D, Geibel S Mycobacterium tuberculosis or strategy and mediate the uptake (2020) Substrate Interaction with the Staphylococcus aureus have of essential nutrients. The group ,ZZ**V\WSPUN7YV[LPUVM[OL;`WL=00I evolved sophisticated nanomachines investigates ESX-3, which is essential Secretion System. Journal of Bacteriology 202(7): embedded in the bacterial cell to pathogen growth in response to e00646-19 envelope to orchestrate the secretion iron-limiting conditions suggesting of virulence factors, which play a role for ESX-3 in counteracting Famelis N, Rivera-Calzada A, Deglies- important roles in pathogenesis. The host defense mechanisms that posti G, Wingender M, Mietrach N, Skehel JM, Fernandez-Leiro R, group is interested in understanding restrict iron availability. Moreover, Böttcher B, Schlosser A, Llorca O, the molecular mechanisms of type ,:? LќLJ[VY WYV[LPUZ OH]L ILLU Geibel S (2019) (YJOP[LJ[\YL VM [OL VII secretion systems (T7SSs) implicated in mycobacterial evasion Figure 2: Crystal structure of the T7SSb substrate recognition domain. T`JVIHJ[LYPHS [`WL =00 ZLJYL[PVU using an interdisciplinary approach of phagocytosis and suppression of system. Nature 576(7786):321-325 combining structural (cryo-EM, X-ray T-helper cell activation. The ESX-3 crystallography) with biochemical secretion machinery is therefore an García-Fernández E, Koch G, Wagner methods. A better structural and attractive new target for antimicrobial T7SSb. To date, substrate recognition derived a general model for the type viously unknown second substrate RM, Fekete A, Stengel ST, Schneider J, mechanistic understanding of these strategies against an essential, intrinsic HUKZLJYL[PVUVM,::LќLJ[VYWYV[LPUZ =00TLKPH[LKLќLJ[VYWYV[LPU[YHUZWVY[ on the T7SSb secretion Mielich-Süss B, Geibel S, Markert SM, Stigloher C, Lopez D (2017) Membrane systems will aid the design of novel bacterial process involved in metal are poorly understood due to the The ESX-3 complex spans the machine (Mietrach et al., 2020, 4PJYVKVTHPU +PZHZZLTIS` 0UOPIP[Z antimicrobial strategies targeting homeostasis, as well as promoting lack of structural information on the inner mycobacterial membrane and J Bacteriol). The crystal structure of 49:((U[PIPV[PJ9LZPZ[HUJL. mycobacteria, methicillin-resistant host by restoring the membrane embedded secretion [YHUZSVJH[LZLќLJ[VYWYV[LPUZMYVT[OL the substrate recognition domain Cell 171(6):1354-1367.e20 S. aureus (MRSA), and other patho- immune response. However, neither machine and its interaction with cytoplasm into the periplasmic space, provides the structural basis for gens that depend on T7SSs for host the ESX-3 secretion mechanism nor substrates. from where further transport across rational drug design/fragment-based Mielich-Süss B, Wagner RM, Mietrach N, Hertlein T, Marincola G, Ohlsen K, infections. the mechanism linking the secreted the outer mycobacterial membrane screens to block substrate binding Geibel S, Lopez D (2017)-SV[PSSPUZJHќVSK ,:?LќLJ[VYWYV[LPUZ[VPYVUPTWVY[ occurs by a yet unknown mechanism. to this recognition domain. These HJ[P]P[` JVU[YPI\[LZ [V [`WL =00 ZLJYL[PVU Tuberculosis is a highly infectious is currently understood. HIGHLIGHTS & OUTLOOK A cytosolic vestibule-like structure compounds could serve as novel non- system assembly in Staphylococcus disease that is caused by various constitutes 24 loosely packed ATPase bactericidal antibiotics that target the aureus. PLoS Pathogens 13(11):e1006728 strains of mycobacteria. According to In parallel, the group is pursuing the To gain insights into the mycobacterial domains, which create the mechanical T7SSb and thereby restore the host YLJLU[ ÄN\YLZ MYVT [OL >VYSK /LHS[O structural and functional investigation T7SS mechanism, the group has motion for substrate secretion by immune response. Organization (WHO), it accounts of the T7SSb found in pathogenic reconstituted a stable core complex cycling through conformational states for 1.5 million deaths every year. staphylococci such as the methicillin- of the ESX-3 secretion machine of ATP binding and ATP hydrolysis. resistant strain S. aureus USA300 [OH[ JVU[HPUZ MV\Y V\[ VM Ä]L (MRSA). S. aureus is the leading membrane proteins (Figure 1) and The investigation of the T7SSb led to cause of bacteremia, endocarditis, determined its three-dimensional [OL PKLU[PÄJH[PVU HUK JY`Z[HSSPaH[PVU osteomyelitis, as well as skin, soft structure using single particle cryo- of an essential extracellular domain tissue, pulmonary, and device-related electron microscopy (cryo-EM) of this system (Mietrach et al., 2019, PUMLJ[PVUZ ,ќLJ[VY WYV[LPUZ ZLJYL[LK taking advantage of the recently Acta Cryst F). The group is pursuing by the T7SSb promote bacterial established state-of-the-art electron its structural determination by X-ray abscess formation and persistent microscopy facility at the University of crystallography and has also taken infections in murine infection models. Würzburg (Rudolf Virchow Center for ÄYZ[ Z[LWZ [V^HYKZ [OL YLJVUZ[P[\[PVU The T7SSb is distantly related to Experimental Biomedicine). and structure determination of the mycobacterial ESX systems through membrane embedded secretion (i) a subset of secreted proteins The cryo-EM structure resolved for machine by cryo-EM (Miehlich-Süss belonging to the ESX virulence factor [OL ÄYZ[ [PTL HSS WYV[LPU JVTWVULU[Z et al., 2017, PLoS Pathog). The group family and (ii) a motor ATPase of the in the ESX-3 complex and provided has determined the high-resolution FtsK/SpoIIIE ATPase family suggesting unprecedented insights into the structure of a substrate recognition that both systems use similar substrate architecture of mycobacterial type VII domain of the T7SSb. A secretion targeting mechanisms. Unlike in secretion machines (Famelis et al., assay as a functional readout of the diderm mycobacteria, secreted pro- 2019, Nature). Using secretion assays T7SSb was established and used to teins pass a monoderm cell wall in combination with mutagenesis characterize essential amino acids in Figure 1: Model of the type VII secretion system. Left: side view of the ESX-3 nanomachine. Right: top in S. aureus PUKPJH[PUN H KPќLYLU[ Z[\KPLZ [OL NYV\W KLÄULK Z[Y\J[\YHS the substrate binding pocket (Figure 2). view of the central membrane pore; the green periplasmic exit pore was cut away for clarity. architecture of ESX systems and the elements required for transport and Furthermore, we discovered a pre-

28 29 2 ZINF YOUNG INVESTIGATORS

REGULATORY NETWORKS IN PATHOGENESIS

DR. J. CHRISTIAN PÉREZ Research Center for Infectious Diseases Interdisciplinary Center for Clinical Research (IZKF) [email protected] I +49 931 31 83815 www.imib-wuerzburg.de

RESEARCH INTERESTS unrecognized. C. albicans is the most SELECTED PUBLICATIONS prominent fungal species residing in Moreno-Velásquez SD, Tint SH, del The group studies the regulatory humans. While C. albicans can thrive in Olmo Toledo V, Torsin S, De S, Pérez JC circuitry that enables the human multiple niches within the human body (2020) ;OL YLN\SH[VY` WYV[LPUZ 9[N commensal and opportunistic fungal (LN mouth, skin, gastrointestinal and NV]LYU ZWOPUNVSPWPK OVTLVZ[HZPZ PU pathogen, *HUKPKH HSIPJHUZ, to genitourinary tracts), it most frequently [OL O\THU HZZVJPH[LK `LHZ[ *HUKPKH albicans. JVSVUPaLKPќLYLU[UPJOLZPU[OLO\THU dwells in the gut. The majority of Cell Reports 30(3):620-629 body. C. albicans serves as a model healthy adults carry C. albicans as system to gain insights into the general part of their normal gut microbiota. del Olmo Toledo V, Puccinelli R, Fordyce strategies employed by members In addition to being a human PM, Pérez JC (2018) +P]LYZPÄJH[PVU VM +5( IPUKPUN ZWLJPÄJP[PLZ LUHISLK of the microbiota to proliferate as commensal, C. albicans is a common :9,)7 [YHUZJYPW[PVU YLN\SH[VYZ [V harmless commensals and how cause of fastidious mucosal disease in L_WHUK [OL YLWLY[VPYL VM JLSS\SHY some of these microbes become life- otherwise healthy people. It is also the Figure 2: C. albicans engulfed by human neutrophils. M\UJ[PVUZ [OH[ [OL` NV]LYU PU M\UNP. threatening pathogens. major cause of life-threatening fungal YFP reporter localizes to fungal nuclei upon engulfment (arrows). Asterisks denote free fungal cells. PLoS Genetics 14(12):e1007884 infections. In European countries, Meir J, Hartman E, Eckstein MT, The human body harbors a large the incidence of invasive candidiasis Guiducci E, Kirchner F, Rosenwald variety of non-bacterial microbes. is around 10 cases per 100,000 KPZZLTPUH[LK PUMLJ[PVU ;OPZ ÄUKPUN Finally, we have examined a group mice, which we co-colonize with the A, LeibundGut-Landmann S, Pérez Research on this non-bacterial inhabitants and 1.09 cases per 1,000 highlights the distinct features of the of transcription regulators that had fungus, individual gut bacteria, and JC (2018) 0KLU[PÄJH[PVU VM *HUKPKH HSIPJHUZ YLN\SH[VY` NLULZ NV]LYUPUN ÅVYH OV^L]LY OHZ SHNNLK ILOPUK hospital admissions. The mortality C. albicans-host interplay in the oral expanded in the lineage giving rise to KLÄULK TPJYVIPHS JVTT\UP[PLZ >L T\JVZHSPUMLJ[PVU compared to prokaryotes. Fungi, in associated with these infections cavity. C. albicans. While in most eukaryotes expect that these studies reveal novel Cellular Microbiology 20(8):e12841 particular, remain underrepresented approaches 40%, underscoring the this family of regulators governs lipid aspects of the biology of C. albicans in microbiota studies. This is despite need for novel therapeutics to treat We have also investigated the overall biosynthesis, the three copies in in the mammalian intestine. Böhm L, Torsin S, Tint SH, Eckstein MT, the fact that fungi play major roles and prevent this disease. role of two regulatory proteins that C. albicans OH]L HJX\PYLK KPќLYLU[ Ludwig T, Pérez JC (2017) ;OL `LHZ[ MVYT VM [OL M\UN\Z *HUKPKH HSIPJHUZ in microbial community stability and C. albicans needs to successfully functions, some of which contribute to WYVTV[LZ WLYZPZ[LUJL PU [OL N\[ VM human disease. Fungi infect billions colonize the mammalian host. While the ability of C. albicans to reside in the NUV[VIPV[PJTPJL of people every year and cause HIGHLIGHTS & OUTLOOK these regulators had previously been human host and cause disease. We PLoS Pathogens 13(10):e1006699 diseases that kill millions of individuals linked to nitrogen metabolism in found that, despite a conserved overall creating a burden on society similar We have looked at the interplay model yeasts, we recently reported structure, several members of the to tuberculosis and malaria. Yet, between the fungus C. albicans and that in C. albicans - a close relative MHTPS` L_OPIP[LK Z\IZ[HU[PHSS` KPќLYLU[ the contribution of fungi to the [OL VYHS T\JVZH :WLJPÄJHSS` ^L of the model yeast Saccharomyces +5(IPUKPUN ZWLJPÄJP[PLZ! ZVTL global burden of disease is largely screened a collection of C. albicans cerevisiae  [OL YLN\SH[VYZ» THPU proteins bound non-palindromic DNA deletion strains in a mouse model function is connected to lipid biology. sequences whereas others bound a of oral infection. To our knowledge, 6\Y Z[\K` WYV]PKLK [OL ÄYZ[ Z`Z[L palindromic motif. Ancestral protein [OPZ PZ [OL ÄYZ[ YLWVY[ VM H NLUL[PJ matic and quantitative examination of reconstruction experiments indicated screen in an animal model of mucosal the whole C. albicans lipidome. We that the likely family ancestor could candidiasis. Through detailed analy- believe this dataset will become a key bind both the non-palindromic as well ses of the infected mucosae and the resource for researchers interested as the palindromic DNA sequence. host response to wildtype and in one in lipids and will pave the way for ;OLKPќLYLU[+5(IPUKPUNZWLJPÄJP[PLZ VM [OL PKLU[PÄLK *HUKPKH mutants, the exploration of this major class observed in extant members of the we revealed a regulatory gene that of molecules in the context of host- MHTPS` YLÅLJ[ [OLYLMVYL [OL WHY[P[PVU explicitly governs persistence of pathogen interactions. Starting with a VM[OLHUJLZ[VY»Z+5(IPUKPUNWYVÄSL the fungus in the oral cavity and comprehensive survey of metabolites rather than the acquisition of a novel Ä[ULZZ K\YPUN ]HNPUHS PUMLJ[PVUZ 6\Y and lipids, and through extensive trait. This study provides a singular study thus opened the door to the characterization of the inner workings example of the origins of fungal unbiased and systematic discovery of the regulators in C. albicans, we transcription factors associated with of fungal determinants contributing to discovered a mechanism whereby the regulation of pathogenesis traits. mucosal disease. We also found that sphingolipid homeostasis is linked to there was a minimal overlap in “hits” nutrient sensing in this organism. This We are incorporating high resolution between the oral candidiasis screen work implicates sphingolipids, a class Å\VYLZJLUJL TPJYVZJVW` [V V\Y and comparable screens that we of molecules that is starting to receive studies of uncharacterized C. albicans Figure 1: C. albicans (black triangles) penetrating mouse oral mucosa. had previously conducted in mouse a lot of attention in cell and molecular transcription regulators. A major KT, keratinized tissue; E, epithelium; CT, connective tissue. models of intestinal colonization and biology, in C. albicans pathogenesis. focus now is the gut of gnotobiotic

30 31 INSTITUTE OF MOLECULAR INFECTION BIOLOGY

INSTITUTE FOR HYGIENE AND MICROBIOLOGY

INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY, DEPARTMENT OF VIROLOGY 3 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY, DEPARTMENT OF IMMUNOLOGY MEMBERS OF DEPARTMENT OF MICROBIOLOGY, THE ZINF THEODOR BOVERI INSTITUTE, BIOCENTER

DEPARTMENT OF INTERNAL MEDICINE II

INSTITUTE OF SYSTEMS IMMUNOLOGY

HELMHOLTZ INSTITUTE FOR RNA-BASED INFECTION RESEARCH

ZINF MEMBERS ASSOCIATED WITH OTHER INSTITUTES 3.1 INSTITUTE OF MOLECULAR INFECTION BIOLOGY

JÖRG VOGEL

CYNTHIA SHARMA

HEIDRUN MOLL

JOACHIM MORSCHHÄUSER

KNUT OHLSEN

ALEXANDER WESTERMANN

WILMA ZIEBUHR

The Institute of Molecular Infection Biology (IMIB) was founded in 1993 together with the Research Center for Infectious Diseases (ZINF) and is an interdisciplinary research institution within the Medical Faculty of the University of Würzburg, with strong ties to the Faculty of Biology. Prof. Dr. Jörg Vogel has been the director of IMIB and Chair of Molecular Infection Biology since 2009. In 2017, Prof. Dr. Cynthia Sharma was appointed as Chair of the newly established Department of Molecular Infection Biology II.

Members of the Institute investigate fundamental biological processes and molecular mechanisms, with a focus on pathogens and infectious diseases. Research at the IMIB involves the study of bacteria, viruses, parasites, and fungi, as well as their eukaryotic hosts and the interaction with the microbiome. Research activities range from prokaryotic and eukaryotic cell biology and immunology to fundamental aspects of gene regulation and RNA biology, as well as the development of novel 3D infection models. Furthermore, the Institute is home to the groups of the prestigious ZINF Young Investigator program.

ImaImagemagemmaagage: UniUn versiersis tyy o of WürzWü burgburgrg

34 35 3.1 INSTITUTE OF MOLECULAR INFECTION BIOLOGY

RNA BIOLOGY DEEP SEQUENCING APPROACHES TO PATHOGENESIS

PROF. JÖRG VOGEL PROF. CYNTHIA SHARMA Chair of Molecular Infection Biology I, Institute of Molecular Infection Biology Chair of Molecular Infection Biology II, Institute of Molecular Infection Biology Helmholtz Institute for RNA-based Infection Research [email protected] I +49 931 31 82560 [email protected] I +49 931 31 82576 www.imib-wuerzburg.de www.imib-wuerzburg.de I www.helmholtz-hiri.de

RESEARCH INTERESTS small regulatory RNAs, LN., SdhX RESEARCH INTERESTS RBPs of H. pylori and C. jejuni. Besides SELECTED PUBLICATIONS and NarS. These studies bolstered SELECTED PUBLICATIONS new mechanisms of riboregulation, Imdahl F, Vafadarnejad E, Homberger Non-coding RNAs play important V\Y WYL]PV\Z ÄUKPUNZ [OH[ »<;9Z Eisenbart SK*, Alzheimer M*, Pernitzsch Our research focuses on mechanisms ^L OH]L PKLU[PÄLK ZL]LYHS ]PY\SLUJL C, Saliba AE, Vogel J (2020) :PUNSLJLSS regulatory roles in all domains of of mRNAs constitute a rich source SR, Dietrich S, Stahl S, Sharma CM of gene regulation in the gastric associated sRNAs, such as H. pylori 95(ZLX YLWVY[Z NYV^[O JVUKP[PVU life. The group aims to understand of regulatory small RNAs; similar (2020) ( YLWLH[HZZVJPH[LK ZTHSS 95( pathogen Helicobacter pylori and sRNAs that can impact pathogenesis ZWLJPÄJ NSVIHS [YHUZJYPW[VTLZ VM the role of ncRNAs and RNA- sRNAs are now being reported in JVU[YVSZ [OL THQVY ]PY\SLUJL MHJ[VYZ VM the related foodborne pathogen by controlling chemotaxis or LPS PUKP]PK\HSIHJ[LYPH Helicobacter pylori. Nature Microbiology 5(10):1202-1206 binding proteins (RBPs) in the THU` KPќLYLU[ IHJ[LYPHS ZWLJPLZ >L Molecular Cell in press, doi: 10.1016/j. Campylobacter jejuni. We are espe- biogenesis genes, or even act as context of bacterial infections, with also made much progress on the molcel.2020.09.009 cially interested in post-transcriptional central regulators of major virulence Stapels DAC, Hill PWS, Westermann AJ, the goal to use this knowledge for characterization of new RBPs, with regulation during stress response and factors. Fisher RA, Thurston TL, Saliba AE, targeted manipulation of the human a focus on ProQ and FinO domain Alzheimer M, Svensson SL, König F, virulence by small regulatory RNAs Blommestein I, Vogel J, Helaine S Schweinlin M, Metzger M, Walles H, (2018) :HSTVULSSHWLYZPZ[LYZ\UKLYTPUL microbiota. The current four main proteins. Using a UV CLIP-seq Sharma CM (2020) ([OYLLKPTLUZPVUHS (sRNAs) and associated RNA-binding Using our 3D intestinal tissue model, OVZ[PTT\ULKLMLUZLZK\YPUNHU[PIPV[PJ areas of research in the Vogel lab are: approach in Salmonella, we provided PU[LZ[PUHS [PZZ\L TVKLS YL]LHSZ MHJ[VYZ proteins (RBPs). We have been we have demonstrated a role in treatment. i) discovery of novel functional RNAs in evidence that ProQ is truly a global HUKZTHSSYLN\SH[VY`95(ZPTWVY[HU[MVY employing diverse deep sequencing colonization for a C. jejuni sRNA, which Science 362(6419):1156-1160 microbes, which includes work on the RBP that appears to recognize its JVSVUPaH[PVU^P[O*HTW`SVIHJ[LYQLQ\UP. approaches for global transcriptome YLWYLZZLZ H NLUL PU]VS]LK PU ÅHNLSSPU PLoS Pathogens 16(2):e1008304 cancer-associated bug Fusobacterium many cellular RNA targets by a and translatome analysis as well as TVKPÄJH[PVU )HZLK VU ;UZLX HUK Saliba AE, Li L, Westermann AJ, Appenzeller S, Stapels DAC, Schulte LN, nucleatum; ii) characterization of and structural code (rather than primary Dugar G, Leenay RT, Eisenbart SK, to study RNA-protein complexes dual RNA-seq applied during infection Helaine S, Vogel J (2017) :PUNSL JLSS screens for bacterial RNA-binding sequence) that remains to be cracked. Bischler T, Aul BU, Beisel CL#, and have also been developing new of the 3D model, we have been 95(ZLX [PLZ THJYVWOHNL WVSHYP proteins; iii) new RNA-seq methods for 0U HKKP[PVU ^L KLÄULK WH[O^H`Z Sharma CM# (2018) *90:79 95( approaches to globally capture RBPs. identifying additional factors important aH[PVU [V NYV^[O YH[L VM PU[YHJLSS\SHY KLWLUKLU[ IPUKPUN HUK JSLH]HNL Salmonella. infection biology, including single-cell including virulence control in which VM LUKVNLUV\Z 95(Z I` [OL Using three-dimensional (3D) infection for host-pathogen interactions. Nature Microbiology 2:16206 RNA-seq of eukaryotic and bacterial ProQ-mediated gene regulation plays Campylobacter jejuni Cas9. models based on tissue engineering, cells; iv) antisense oligonucleotide an important role. Molecular Cell 69(5):893-905.e7 we are investigating the roles of Using co-IP combined with RNA-seq (ASO)-based antibiotics for precision (DGHM Paper of the Month Award) sRNAs and RBPs in virulence of these (RIP-seq) in C. jejuni^LOH]LPKLU[PÄLK AWARDS editing of the human microbiome and RNA-seq remains a core technology in widespread human pathogens. THU` ÅHNLSSHY T95(Z IV\UK [V [OL Feldberg Prize – Feldberg Foundation complex microbial communities. the lab. A clear highlight in the 2018- Dugar G, Svensson SL, Bischler T, RBP CsrA, which, together with its MVY (UNSV.LYTHU ZJPLU[PÄJ L_JOHUNL 2019 period was our joint publication Wäldchen S, Reinhardt R, Sauer M, protein antagonist FliW, regulates (2019) Sharma CM (2016) ;OL *ZY(-SP> in Science with Sophie Helaine, UL[^VYR JVU[YVSZ WVSHY SVJHSPaH[PVU VM HIGHLIGHTS & OUTLOOK SVJHSPaH[PVU VM [OL ÅHNLSSPU T95( [V HIGHLIGHTS & OUTLOOK in which we used our previously [OL K\HSM\UJ[PVU ÅHNLSSPU T95( PU the cell poles. While CRISPR-Cas9 developed dual RNA-seq technology Campylobacter jejuni. Using , biochemical, molec- nucleases are well known to cleave Nature Communications 7:11667 Highlights of functional RNA studies to study intracellular persister forms of ular biology, and genetics approaches, DNA, RIP-seq of C. jejuni Cas9 revealed were the successful characterization Salmonella. Contrary to expectation, we are elucidating the roles and that it can bind and cleave endogenous in Salmonella VM UL^ » LUKKLYP]LK we found that these seemingly molecular mechanisms of sRNAs and RNAs in a crRNA-guided manner. “dormant” bacteria maintain meta- We also showed that RNA targeting bolism and secrete virulence factors by CjCas9 is programmable in vitro, to actively manipulate their host cells. thereby providing new technological opportunities. We are now further On new RNA-centric technologies for studying the potential impact of Cas9 infection biology, we are now working on endogenous gene regulation. hard to make single-cell RNA-seq a standard technique for the analysis of

36 37 3.1 INSTITUTE OF MOLECULAR INFECTION BIOLOGY

INFECTION IMMUNOLOGY MYCOLOGY

PROF. HEIDRUN MOLL PROF. JOACHIM MORSCHHÄUSER Institute of Molecular Infection Biology Institute of Molecular Infection Biology [email protected] I +49 931 31 82627 [email protected] I +49 931 31 82152 www.imib-wuerzburg.de www.imib-wuerzburg.de

RESEARCH INTERESTS have considerable negative impact RESEARCH INTERESTS clinical isolates usually contain a SELECTED PUBLICATIONS VU [OL LѝJHJ` VM ]HJJPUH[PVU HUK SELECTED PUBLICATIONS combination of these resistance Firdessa R, Good L, Amstalden MC, Leishmaniasis is a neglected tropical the chemotherapeutic strategies. Mayr EM*, Ramírez-Zavala B* , Krüger I, The yeast *HUKPKH HSIPJHUZ is a mechanisms and are homozygous Chindera K, Kamaruzzaman NF, disease with more than 1.3 million Our collaboration partners have Morschhäuser J (2020) A Zinc Cluster harmless commensal in most healthy for the mutated alleles, which Schultheis M, Röger B, Hecht N, new cases and 30,000 deaths per demonstrated an exhausted T-cell ;YHUZJYPW[PVU -HJ[VY *VU[YPI\[LZ [V people, but it can also cause mucosal further increases . To Oelschlaeger TA, Meinel L, Lühmann T, year worldwide. Climate change Z[H[\Z TLKPH[LK I` ZPNUPÄJHU[S` [OL 0U[YPUZPJ -S\JVUHaVSL 9LZPZ[HUJL VM as well as life-threatening systemic understand how such strains evolve, Moll H (2015) 7H[OVNLU HUK OVZ[ *HUKPKHH\YPZ KPYLJ[LK HU[PSLPZOTHUPHS LќLJ[Z HSSV^Z [OL ZHUK Å` HUK [OL WHYHZP[L elevated surface expression of co- mSphere 5(2):e00279-20 infections. Our group studies the we used a set of isogenic strains TLKPH[LKI`WVS`OL_HUPKL7/4) to spread from the South, where the inhibitory molecules (PD-1/PD-L1) in regulation of virulence traits, the role of [OH[ ^LYL OL[LYVa`NV\Z MVY KPќLYLU[ PLoS Neglected Tropical Diseases disease is already endemic, to more patients with chronic leishmaniasis. Mottola A, Morschhäuser J (2019) metabolic adaptation in pathogenicity, Å\JVUHaVSLYLZPZ[HUJLT\[H[PVUZHUK 9(10):e0004041 northern regions. Unsatisfactory anti- Blockade of the PD-1 thus (U PU[YHNLUPJ YLJVTIPUH[PVU L]LU[ and the evolution of drug resistance thus displayed moderately increased NLULYH[LZ H :UMPUKLWLUKLU[ MVYT Gonzalez-Leal IJ, Roeger B, Schwarz A, leishmanial treatment options stress may promote the rescue of CD4+ and VM [OL LZZLU[PHS WYV[LPU RPUHZL :UM PU in C. albicans to better understand drug resistance. When these strains Schirmeister T, Reinheckel T, Lutz MB, the importance of developing inex- CD8+ T cell functions and induced the *HUKPKHHSIPJHUZ how this important fungal pathogen were propagated in the presence Moll H (2014) *H[OLWZPU)PUHU[PNLU WLUZP]LLќLJ[P]LHUKYHWPK[OLYHWPLZ clearance of parasites. Ethical issues mSphere 4(3):e00352-19 HKHW[Z[VKPќLYLU[UPJOLZHUKHS[LYLK VM Å\JVUHaVSL [OL` YHWPKS` L]VS]LK WYLZLU[PUN JLSSZ JVU[YVSZ TLKPH[VYZ against leishmaniasis. make the direct study of lesional environmental conditions during colo- further increased resistance by loss VM [OL ;O PTT\UL YLZWVUZL K\YPUN lymphocyte function in patients Popp C, Ramírez-Zavala B, Schwanfelder nization and infection. of heterozygosity for the mutated 3LPZOTHUPHTHQVYPUMLJ[PVU S, Krüger I, Morschhäuser J (2019) PLoS Neglected Tropical Diseases challenging, therefore we propose ,]VS\[PVU VM Å\JVUHaVSLYLZPZ[HU[ alleles. This was often accompanied 8(9):e3194 HIGHLIGHTS & OUTLOOK studies with check-point inhibitors in *HUKPKH HSIPJHUZ Z[YHPUZ I` KY\N by homozygosity at the mating type the murine infection model. PUK\JLK TH[PUN JVTWL[LUJL HUK HIGHLIGHTS & OUTLOOK locus (4;3), which allowed the cells Firdessa R, Oelschlaeger TA, Moll H parasexual recombination. (2014) 0KLU[PÄJH[PVU VM T\S[PWSL JLSS\SHY We have shown that successful mBio 10(1):e02740-1 to switch to the mating-competent parasitism requires Leishmania to Standard of care therapies (miltefosine, C. albicans can develop resistance opaque morphology. Opaque cells \W[HRL WH[O^H`Z VM WVS`Z[`YLUL UHUV (DGHM Paper of the Month Award) WHY[PJSLZHUKMHJ[VYZHќLJ[PUN[OL\W[HRL! survive and proliferate in their host amphotericin B, antimonies) in use [V [OL HU[PT`JV[PJ KY\N Å\JVUHaVSL ^P[O KPќLYLU[ YLZPZ[HUJL T\[H[PVUZ 9LSL]HUJLMVYKY\NKLSP]LY`Z`Z[LTZ cells, predominantly macrophages against leishmaniasis lead to a similar which inhibits ergosterol biosynthesis mated with each other to produce European Journal of Cell Biology Ramírez-Zavala B, Manz H, Englert F, 93(8-9):323-337 and dendritic cells (DC), and we curative outcome independent of Rogers PD, Morschhäuser J (2018) and is widely used to treat fungal tetraploid cells that contained understand that this ultimately their mechanisms of drug action, ( O`WLYHJ[P]L MVYT VM [OL aPUJ JS\Z[LY infections. Besides mutations in genetic material from both parents. [YHUZJYPW[PVU MHJ[VY :[I JH\ZLZ @69 Schwarz T, Remer KA, Nahrendorf blocks the production of the Th1- and the data of a platinum- V]LYL_WYLZZPVU HUK ILH\]LYPJPU YLZPZ the drug target , activating The mating products reassorted W, Masic A, Siewe L, Müller W, Roers inducing cytokine IL-12. Both CD8+ derivative used to cure mice from [HUJLPU*HUKPKHHSIPJHUZ mutations in transcription factors their merged genomes and, under A, Moll H (2013) ; *LSS+LYP]LK 03 and CD4+ T cell populations contain leishmaniasis indicated a strong Antimicrobial Agents and Chemo- that result in the constitutive selective pressure by the drug, Determines Leishmaniasis Disease therapy 62(12):e01655-18 6\[JVTL HUK 0Z :\WWYLZZLK I` H antigen-experienced cells that do partition of the immune system. overexpression of genes encoding generated progeny cells that retained +LUKYP[PJ*LSS)HZLK=HJJPUL not respond to antigen but also do This compares to of ergosterol biosynthesis and the advantageous mutated alleles PLoS Pathogens 9(6):e1003476 not undergo apoptosis. Hence, T-cell tumors, where selected therapeutics T\S[PKY\NLў\_W\TWZHYLHMYLX\LU[ while returning to the diploid state. exhaustion during leishmaniasis may (cyclophosphamide, doxorubicin, ox- cause of resistance. Highly resistant ;OLYLMVYL Å\JVUHaVSL [YLH[TLU[ UV[ aliplatin, mitoxantrone, patupilone) only selects for resistance mutations elicit immunogenic cell death, a but also promotes genomic alterations [\TVYZWLJPÄJ *+ KYP]LU PTT\UL that confer mating competence, response associated with the which allows the cells to exchange induction of DC, Calreticulin, HSP90, individually acquired resistance and a release of ATP and HMGB1. mechanisms and generate highly We suggest to establish immunogenic drug-resistant progeny. cell death (ICD)-enhancing strategies in combination with new Leishmania- We are currently using libraries of targeted drugs. Inhibitors of the activated transcription factors and parasite proteins CK1.2, HSP90/ protein kinase deletion mutants, which HSP83 may have a better therapeutic are central components of signaling ^PUKV^ JVTWHYLK [V [VKH`»Z pathways, to study the regulatory repositioned old cancer drugs and in networks controlling morphogenesis, addition to an ICD-enhancing strategy metabolic adaptation, and other may support long lasting anti-parasite virulence traits of C. albicans. immunity.

Fluorescence microscopy images of BMDMs after 30 minutes of incubation with 20 nm nanoparticles Mating of C. albicans JLSSZ ^P[O KPќLYLU[ Å\JVUHaVSL YLZPZ[HUJL T\[H[PVUZ SHILSLK NYLLU HUK YLK (green) showing co-localization with the endosomal marker FM4-64FX (red). generating recombinant progeny cells (yellow).

38 39 3.1 INSTITUTE OF MOLECULAR INFECTION BIOLOGY

GRAM-POSITIVE COCCI HOST-PATHOGEN-MICROBIOTA INTERACTIONS

DR. KNUT OHLSEN JUN. PROF. ALEXANDER WESTERMANN Institute of Molecular Infection Biology Institute of Molecular Infection Biology Helmholtz Institute for RNA-based Infection Research [email protected] I +49 931 31 82155 www.imib-wuerzburg.de [email protected] I +49 931 31 83781 www.imib-wuerzburg.de I www.helmholtz-hiri.de

RESEARCH INTERESTS novel trisindolyl cycloalkanes. First RESEARCH INTERESTS infections we may not necessarily SELECTED PUBLICATIONS SLHK JVTWV\UKZ JV\SK IL PKLU[PÄLK SELECTED PUBLICATIONS have to inhibit the pathogen directly, Fan SH, Ebner P, Reichert S, Hertlein Gram-positive pathogens are the with promising activities similar to Ryan D, Jenniches L, Reichardt S, Bacterial infections of mammalian but we may instead foster competing T, Zabel S, Lankapalli AK, Nieselt K, leading cause of hospital-acquired used antibiotics of last resort in vitro. Barquist L, Westermann AJ (2020) A hosts are arguably highly complex commensals. By advancing multi- Ohlsen K, Götz F (2019) MpsAB is infections. Our main research OPNOYLZVS\[PVU [YHUZJYPW[VTL THW biological processes. How do enteric organism RNA-seq approaches (LN PTWVY[HU[ MVY :[HWO`SVJVJJ\Z H\YL\Z interest is the development of novel We are also interested in the regulation PKLU[PÄLZ ZTHSS 95( YLN\SH[PVU VM TL[H bacterial pathogens promote infection metatranscriptomics, dual and triple ]PY\SLUJL HUK NYV^[O H[ H[TVZWOLYPJ IVSPZT PU [OL N\[ TPJYVIL )HJ[LYVPKLZ strategies against multiresistant of cellular functions by eukaryotic- and what defense mechanisms do RNA-seq), we analyze the dynamic CO2 levels. thetaiotaomicron. Nature Communications 10(1):3627 staphylococci and enterococci and like serine/threonine kinases and Nature Communications 11(1):3557 they have to overcome in order to interplay of the host and its microbiota application of in-vivo models to study phosphatases. To understand the colonize the gut? What molecular with invading pathogens. Stapels DAC, Hill PWS, Westermann Hilgeroth A, Yasrebi K, Suzen S, ]PY\SLUJL TLJOHUPZTZ HUK LѝJHJ` cellular role of these enzymes, mechanisms manifest the protective Hertlein T, Ohlsen K, Lalk M (2019) AJ, Fisher R, Thurston TL, Saliba A-E, (U[PIHJ[LYPHS ,]HS\H[PVU VM 5V]LS :\I of novel antibacterials. In particular, designated Stk and Stp, in S. aureus Blommestein I, Vogel J, Helaine S role of the intestinal microbiota against The anaerobic )HJ[LYVPKLZ [OL[H Z[P[\[LK*`JSVOLW[HPUKVSLZPU:[HWO`SV we have a track record in animal we have elucidated the interaction (2018):HSTVULSSHWLYZPZ[LYZ\UKLYTPUL pathogenic attack? And what is the role iotaomicron represents one of the coccus & Enterococcus Strains. models, evaluation of antibacterials, WHY[ULYZ VM :[R HUK :[W HUK KLÄULK OVZ[PTT\ULKLMLUJLZK\YPUNHU[PIPV[PJ of non-coding RNAs and RNA-binding most prevalent members of the gut Medical Chemistry 15(8):833-83 treatment. determining the mode of action of their function in cell wall biosynthesis. Science 362(6419):1156-1160 proteins in these interactions? These microbiota and emerged as the model antibacterial compounds, and the We have found that post-translational and related questions are addressed bacterium for functional microbiota Seethaler M, Hertlein T, Wecklein B, Ymeraj A, Ohlsen K, Lalk M, Hilgeroth A molecular biology of Staphylococcus TVKPÄJH[PVUZVMJLSS^HSSZ`U[OLZPaPUN Westermann AJ, Förstner KU, in our group. Using cutting-edge RNA- research. By compiling a high- (2019) 5V]LS :THSSTVSLJ\SL (U[P aureus. Current projects particularly enzymes are important to ensure the Amman F, Barquist L, Chao Y, Schulte seq-based techniques in combination resolution transcriptome annotation IHJ[LYPHSZ HNHPUZ[ .YHTWVZP[P]L focus on novel targets for antibiotics, LѝJPLUJ`HUKHJJ\YHJ`VM[OLJLSS^HSS LN, Müller L, Reinhardt R, Stadler with mechanistic studies, our research for this microbiota member (‘Theta- 7H[OVNLUZ VM :[HWO`SVJVJJ\Z HUK PF, Vogel J (2016) +\HS 95(ZLX Enterococcus Species. regulation of resistance and virulence, synthesis machinery in S. aureus (see \U]LPSZ UVUJVKPUN 95( M\UJ[PVUZ PU JLU[LYZ VU [OL PKLU[PÄJH[PVU HUK )HZL»! O[[WZ!IHJ[LYVPKLZOLSTOVS[aOaP Antibiotics 8(4):210 and gene expression analysis during Figure). Salmonella-host interplay. functional characterization of RNA- KL ^L YLJLU[S` PKLU[PÄLK O\UKYLKZ infection. Nature 529(7587):496-501 mediated processes during bacterial of novel non-coding RNAs. In the Jarick M, Bertsche U, Stahl M, Schultz D, Carbon dioxide (CO2) has a growth colonization of the human gut. absence of homologs for known Methling K, Lalk M, Stigloher C, WYVTV[PUN LќLJ[ PU ]HYPV\Z IHJ[LYPH global RNA-binding proteins such Steger M, Schlosser A, Ohlsen K AWARDS HIGHLIGHTS & OUTLOOK including S. aureus. We characterized as Hfq or ProQ, we investigate the (2018) ;OL ZLYPUL[OYLVUPUL RPUHZL Short-Term Fellowship Award by :[RHUK[OLWOVZWOH[HZL:[WYLN\SH[L the role of the inorganic carbon the European Molecular Biology HIGHLIGHTS & OUTLOOK mechanistic aspects of sRNA activity cell wall synthesis in Staphylococcus Recently, we developed, together transporter MpsA in vivo. In a pneu- Organization (EMBO, 2018) in )HJ[LYVPKLZ. Combining multiplexed aureus. with cooperation partners, novel monia model, bacteria lacking MpsA Pathogenic bacteria do not interact CRISPR-based sRNA knockdown 6FLHQWLðF5HSRUWV 8(1):1369 antibacterial compounds targeting had a reduced chance to survive with their host in isolation, but in with advanced three-dimensional bacterial pyruvate kinase for clinical in the lung but not in other organs the presence of the protective primary models of the human colon, application by comprehensive struc- such as kidneys or liver. This bacteria collectively referred to as we aim at identifying sRNAs employed ture-activity relationship analysis of suggests that MpsA is essential for the microbiota. Thus, to combat by B. thetaiotaomicron to colonize S. aureus to establish an infection of its host niche and protect it against

the lung at higher CO2 levels. enteric pathogens.

In the future, we are interested in In summary, we compile networks analyzing expression of bacterial of host, microbiota, and pathogen and host genes during S. aureus factors that shape their triangular infections by applying dual RNA-seq interplay. Biological insights gained methodology. In addition, we are in- from the accompanying mechanistic vestigating the regulation of resistance studies will substantially improve against bisquaternary bisnaph- our knowledge of the functions thalimides by a small RNA. Finally, of regulatory RNA molecules and we have started to use humanized their protein partners in bacterial mice to study the role of human pathogenesis and host protection. ZWLJPÄJ ]PY\SLUJL TLJOHUPZTZ VM This will lay the groundwork needed S. aureus in a mouse model. to exploit RNA biology for diagnostics and therapy against infectious diseases.

Interaction network of Ser/Thr kinase Stk and phosphatase Stp based on the analysis of bacterial two- An RNA-centric view of host-pathogen-commensal interactions. RNA-mediated processes shape host- hybrid studies. microbe interactions (A) and can be studied by dual RNA-seq (B).

40 41 3.1 INSTITUTE OF MOLECULAR INFECTION BIOLOGY

NOSOCOMIAL INFECTIONS BY STAPHYLOCOCCI

DR. WILMA ZIEBUHR Institute of Molecular Infection Biology [email protected] I +49 931 31 82154 www.imib-wuerzburg.de

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK SELECTED PUBLICATIONS Schoenfelder SMK, Lange C, Prakash Our work aims at understanding 3PMLPUIPVÄSTZPZ^PKLZWYLHKPUUH[\YL SA, Marincola G, Lerch MF, Wencker the lifestyle of staphylococci as and is also a typical hallmark of FDR, Förstner KU, Sharma CM, major opportunistic and nosocomial UVZVJVTPHS Z[HWO`SVJVJJP )PVÄSTZ Ziebuhr W (2019) ;OLZTHSSUVUJVKPUN pathogens. Current projects focus on functionally resemble multicellular 95( 9ZH, PUÅ\LUJLZ L_[YHJLSS\SHY matrix composition in Staphylococcus RNA-mediated regulation of virulence organisms in terms of heterogeneous LWPKLYTPKPZIPVÄSTJVTT\UP[PLZ (i.e.IPVÄSTMVYTH[PVUHUKTL[HIVSPZT gene expression patterns. In a PLoS Pathogens 15(3):e1007618 in these Gram-positive bacteria. changing environment, heterogeneity Regarding the latter, we intensively is likely to facilitate persistence Lerch MF, Schoenfelder SMK, Marincola G, Wencker FDR, Eckart M, Förstner study control of KL UV]V methionine and survival of the population as a KU, Sharma CM, Thormann KM, biosynthesis by T-box riboswitches. whole, but may also support division Kucklick M, Engelmann S, Ziebuhr W We also have a long-standing interest VM SHIVY ^P[OPU IPVÄSTZ 9LJLU[S` (2019) ( UVUJVKPUN 95( MYVT [OL in staphylococcal antibiotic resistance ^L PKLU[PÄLK PU Staphylococcus PU[LYJLSS\SHY HKOLZPVU PJH SVJ\Z VM :[HWO`SVJVJJ\Z LWPKLYTPKPZ JVU[YVSZ (ABR). Here, we are engaged in One LWPKLYTPKPZ H ZWLJPLZZWLJPÄJ Z95( WVS`ZHJJOHYPKL PU[LYJLSS\SHY HKOLZPVU Health aspects of staphylococcal (i.e. IcaZ), which is indispensable for 70(TLKPH[LKIPVÄSTMVYTH[PVU epidemiology by analyzing ABR polysaccharide intercellular adhesin Molecular Microbiology 111(6):1571- 1591 WYVÄSLZ VM Z[HWO`SVJVJJP MYVT 70(TLKPH[LK IPVÄST MVYTH[PVU industrialised animal husbandry in in this organism. Also, we studied Marincola G, Wencker FDR, Ziebuhr W Germany. Recently, we extended RsaE (synonym RoxS), which is a (2019) ;OL 4HU` -HJL[Z VM [OL :THSS these analyses, in a joint project with highly conserved sRNA in bacteria of 5VUJVKPUN 95( 9ZH, 9V_: PU colleagues from South Africa, Kenya, the Bacillales order. We found that 4L[HIVSPJ 5PJOL (KHW[H[PVU VM .YHT Positive Bacteria. and Egypt, to various geographic RsaE is heterogeneously expressed Journal of Molecular Biology 431(23): regions in Africa. Finally, we support in :LWPKLYTPKPZ IPVÄSTZ ^OLYL 4684-4698 colleagues from chemistry and P[ PUÅ\LUJLZ L_[YHJLSS\SHY IPVÄST WOHYTHJ` PU [OLPY LќVY[Z [V PKLU[PM` matrix composition. RsaE seems Heilmann C, Ziebuhr W, Becker K (2019) novel lead compounds with anti- to represent a potent riboregulator (YL JVHN\SHZLULNH[P]L Z[HWO`SVJVJJP virulent? staphylococcal growth as well as of central carbon metabolism and Clinical Microbiology and Infection IPVÄSTHJ[P]P[` energy balance with many molecular 2(9):1071-1080 RsaE/RoxS functions and targets being shared across Gram-positive ZWLJPLZ ;OLZL ÄUKPUNZ HZZPNU RsaE/RoxS a prominent role in the adaptation of Gram-positive bacteria to environments with varying nutrient availabilities.

Our future work will focus on the molecular details of IcaZ and RsaE M\UJ[PVUZ PU Z[HWO`SVJVJJHS IPVÄSTZ including their role in metabolic niche KP]LYZPÄJH[PVU HUK WYVNYHTTLK bacterial lysis. Moreover, we will validate T-box riboswitches as novel antibacterial targets by using RNA- mediated methionine biosynthesis control in staphylococci as a tool and proof of principle.

CLSM image of RsaE expression in a :LWPKLYTPKPZIPVÄSTJ`HU"7rsaEJMW reporter fusion). PIA matrix is stained with WGA-AlexaFluor488® (green).

42 43 3.2 INSTITUTE FOR HYGIENE AND MICROBIOLOGY

MATTHIAS FROSCH

OLIVER KURZAI

KLAUS BREHM

CHRISTOPH SCHOEN

ALEXANDRA SCHUBERT-UNKMEIR

ULRICH VOGEL

The Institute for Hygiene and Microbiology (IHM) is part of the Medical Faculty at the University of Würzburg and subdivided into two departments. The Department of Hygiene and Microbiology is headed by Prof. Dr. Matthias Frosch since 1996. Prof. Dr. Oliver Kurzai was appointed as head of the newly established Department of and Mycology at the IHM in 2017.

The IHM provides diagnostics for infectious diseases caused by bacteria, viruses, fungi, and parasites, and advises clinicians on the treatment and prevention of these diseases. Research activities within the IHM focus on the molecular mechanisms involved in the pathogenesis of various infectious diseases. The Institute leads the European Centre for Disease Control and Prevention (ECDC) program “Coordination of activities for laboratory surveillance of Invasive Bacterial Diseases IBD-labnet”. This program is dedicated to monitoring invasive infections caused by 5LPZZLYPH TLUPUNP[PKPZ, Streptococcus pneumoniae, and /HLTVWOPS\ZPUÅ\LUaHLthroughout Europe.

The IHM also hosts the National Reference Laboratories for meningococci and /HLTVWOPS\Z PUÅ\LUaHL (NRZMHI) and the Consiliary Laboratory for echinococcosis. In addition, the Chair of Medical Microbiology and Mycology at the IHM heads the National Reference Center for Invasive Fungal Infections (NRZMyk) located at the Hans Knöll Institute in Jena.

Image: HiHilHi dede MMerkertrke t

44 45 3.2 INSTITUTE FOR HYGIENE AND MICROBIOLOGY

MOLECULAR SURVEILLANCE OF MEDICAL MICROBIOLOGY AND INVASIVE BACTERIAL INFECTIONS MYCOLOGY

PROF. MATTHIAS FROSCH PROF. OLIVER KURZAI Chair of Hygiene and Microbiology, Institute for Hygiene and Microbiology Chair of Medical Microbiology and Mycology, Institute for Hygiene and Microbiology [email protected] I +49 931 31 46160 [email protected] I +49 931 31 88007 www.hygiene.uni-wuerzburg.de www.hygiene.uni-wuerzburg.de

RESEARCH INTERESTS Ulrich Vogel, Alexandra Schubert- RESEARCH INTERESTS human whole blood infection model, SELECTED PUBLICATIONS Unkmeir, and Christoph Schoen, SELECTED PUBLICATIONS we study host-pathogen interactions Moremi N, Claus H, Rutta L, Frosch M, The diversity of bacterial isolates working at the IHM, illustrate these von Lilienfeld-Toal M, Wagener J, Invasive fungal infections in Europe during candidemia. Bioinformatic Vogel U, Mshana SE (2018) /PNO within a species is the focus of research projects in more detail. Einsele H, Cornely OA, Kurzai O (2019) are mainly caused by yeasts in the modeling allows us to determine rates JHYYPHNL YH[L VM L_[LUKLKZWLJ[Y\T research activities at the Department 0U]HZP]L-\UNHS0UMLJ[PVU genus *HUKPKH HUK ÄSHTLU[V\Z VM M\UNHS RPSSPUN I` KPќLYLU[ PTT\UL IL[HSHJ[HTHZLWYVK\JPUN ,U[LYVIHJ of Hygiene and Microbiology. There is Deutsches Ärzteblatt International (ZWLYNPSS\Z species. They primarily cell populations as well as immune [LYPHJLHLHTVUNWH[PLU[ZHKTP[[LKMVY 116(16):271-278 Z\YNLY` PU ;HUaHUPHU OVZWP[HSZ ^P[O H increasing evidence that this diversity HIGHLIGHTS & OUTLOOK HќLJ[ H NYV^PUN U\TILY VM escape of C. albicans. Resolving SV^ YH[L VM LUKVNLUV\Z Z\YNPJHS ZP[L of pathogenic bacteria is key to Wagner L, Stielow JB, de Hoog GS, immunocompromised patients and are the taxonomy of pathogenic fungi PUMLJ[PVUZ understanding the complex interplay Transnational collaborations between Bensch K, Schwartze VU, Voigt K, associated with high mortality. Clinical is important to understand the Journal of Hospital Infection 100(1): between pathogen and host and the European Reference laboratories Alastruey-Izquierdo A, Kurzai O, management of fungal diseases is evolution of virulence. We revisited 47-53 Walther G (2019) A new species correlations between certain bacterial for meningococci, Haemophilus JVUJLW[MVY[OLJSPUPJHSS`YLSL]HU[4\JVY complex due to a growing variety of the taxonomy of the clinically relevant Frosch M (2018) :PNUPÄJHUJL VM ÄUL[`WLZHUK[OLJSPUPJHSWYLZLU[H[PVU PUÅ\LUaHL, and Streptococcus JPYJPULSSVPKLZJVTWSL_ fungal pathogens that include rare and 4\JVY JPYJPULSSVPKLZ complex using [OL KVJ[VYH[L PU ZJPLU[PÄJ TLKPJHS progression and outcome of infec- pneumoniae have been further Persoonia doi: 10.3767/persoonia. new species and the development of molecular and phenotypic traits. LK\JH[PVU tious diseases. 5LPZZLYPHTLUPUNP[PKPZ, promoted on behalf of the ECDC 2020.44.03 antifungal drug resistance in some This resulted in the description of Bundesgesundheitsblatt für Gesund- the meningococcus, is a paradigm (European Centre for Disease Pre- established pathogenic fungi. We  KPZJYL[L ZWLJPLZ PUJS\KPUN Ä]L heitsforschung & Gesundheitsschutz Geißel B, Loiko V, Klugherz I, Zhu Z, 61(2):141-147 of a commensal and pathogenic vention and Control). Within this Wagener N, Kurzai O, van den Hondel investigate the interaction between novel taxa. Importantly, these species bacterium, many variants of which framework, a laboratory network (IBD- CAMJJ, Wagener J (2018) (aVSL fungal pathogens and the human host ZOV^LK JSLHY KPќLYLUJLZ PU [OLPY Klughammer J, Dittrich M, Blom J, colonize the human nasopharynx. labnet) comprised of all Reference PUK\JLKJLSS^HSSJHYIVO`KYH[LWH[JOLZ to elucidate virulence traits as well as HU[PM\UNHSZ\ZJLW[PIPSP[`WYVÄSLZ Mitesser V, Vogel U, Frosch M, RPSS(ZWLYNPSS\ZM\TPNH[\Z Goesmann A, Müller T, Schoen C (2017) However, only a relatively small Laboratories on 5LPZZLYPH TLUPUNP Nature Communications 9(1):3098 YLSL]HU[ LќLJ[VY WH[[LYUZ PU [OL OVZ[ *VTWHYH[P]L .LUVTL :LX\LUJPUN number of these variants, known as [PKPZ, /HLTVWOPS\Z PUÅ\LUaHL, and immune response. Within the National >OLYLHZ Z\ZJLW[PIPSP[` WYVÄSLZ VM 9L]LHSZ >P[OPU/VZ[ .LUL[PJ *OHUNLZ hypervirulent and hyperinvasive types, Streptococcus pneumoniae in the Reference Center for Invasive Fungal Mucor spp. are largely determined by PU5LPZZLYPHTLUPUNP[PKPZK\YPUN0U]HZP]L are associated with severe invasive EU Member States is coordinated AWARDS Infections (NRZMyk), we directly apply primary resistance, azole resistance in Disease. PLoS One 12(1):e0169892 and often lethal disease. Several by the IHM and aims to harmonize Main Research Award of the German V\Y ÄUKPUNZ HUK L_WLY[PZL [OYV\NO (ZWLYNPSS\Z M\TPNH[\Z is an acquired groups at the Institute for Hygiene laboratory surveillance of invasive Society for Hygiene and Microbiology, diagnostic tests and consiliary advice phenotype. We could show that Lam TT, Claus H, Frosch M, Vogel U and Microbiology (IHM) focus on bacterial diseases. The goal is to DGHM (2020) in clinical settings. azoles initially act fungistatically on (2016) (UHS`ZPZ VM UVU[`WLHISL deciphering the basis for virulence, improve laboratory capacities to (M\TPNH[\Z. This is mechanistically /HLTVWOPS\Z PUÅ\LUaHL PU PU]HZP]L analyzing the complex interaction of accurately characterize these invasive separate from their succeeding KPZLHZL YL]LHSZ SHJR VM [OL JHWZ\SL locus. commensal and virulent meningococci IHJ[LYPHS PZVSH[LZ ;V M\SÄSS [OPZ [HZR HIGHLIGHTS & OUTLOOK M\UNPJPKHS LќLJ[ ^OPJO PZ [YPNNLYLK Clinical Microbiology and Infection with the human host and developing the IHM assists the participating by synthesis of cell wall carbohydrate 22(1):63.e7-8 [VVSZMVY[OLPYPKLU[PÄJH[PVUHUK[`WPUN National Reference Laboratories *HUKPKH spp. are a major cause patches that penetrate the plasma The reports of the ZINF members to continuously improve laboratory of bloodstream infections. Using a membrane and kill the fungus. Our performance with respect to the insights into resistance mechanisms PKLU[PÄJH[PVU HUK JOHYHJ[LYPaH[PVU VM and fungal taxonomy are applied to 5LPZZLYPH TLUPUNP[PKPZ, Haemophilus patient care in the NRZMyk, hosted at PUÅ\LUaHL, and Streptococcus the Hans-Knöll-Institute in Jena (Head WUL\TVUPHL as well as the Prof. Dr. Oliver Kurzai). implementation of new techniques for routine diagnosis and typing. In this regard, the IHM is supporting [OL ,*+*»Z Z[YH[LN` HUK YVHKTHW for the integration of molecular typing into laboratory surveillance. Special emphasis lies on the establishment of standards and surveillance systems enabling the EU wide use of whole genome sequencing as the method of choice for typing of meningococcal bacteria.

Microvilli formation induced in human brain endothelial cells upon contact with 5LPZZLYPHTLUPUNP[PKPZ The 4\JVYJPYJPULSSVPKLZ complex consists of 14 discrete species.

46 47 3.2 INSTITUTE FOR HYGIENE AND MICROBIOLOGY

HELMINTH INFECTIONS MOLECULAR DIAGNOSTICS AND FUNCTIONAL GENOMICS OF HUMAN

PROF. KLAUS BREHM PATHOGENIC BACTERIA Institute for Hygiene and Microbiology PROF. CHRISTOPH SCHOEN [email protected] I +49 931 31 46168 Institute for Hygiene and Microbiology www.hygiene.uni-wuerzburg.de [email protected] I +49 931 31 46162 www.hygiene.uni-wuerzburg.de

RESEARCH INTERESTS the Echinococcus metacestode RESEARCH INTERESTS pneumococcal conjugate vaccine SELECTED PUBLICATIONS stage and the development of novel SELECTED PUBLICATIONS (PCV) immunization for infants. In 488 Pérez MG, Spiliotis M, Rego N, 7HYHZP[PJ ÅH[^VYTZ JLZ[VKLZ HUK chemotherapeutics against the Heidrich N, Hagmann A, Bauriedl S, The application of molecular tech- of the 1,447 children with PPE/PE Macchiaroli N, Kamenetzky L, Holroyd trematodes) are a major cause of disease are investigated. Vogel J, Schoen C (2019) ;OL*90:79 niques enables the rapid detection  IHJ[LYPH%ZWLJPLZ^LYL N,Cucher M, Brehm K*, Rosenzvit MC* human disease worldwide. The *HZ Z`Z[LT PU 5LPZZLYPH TLUPUNP[PKPZ of pathogenic microorganisms and detected by 16S rDNA-PCR and/or (2019) +LJPWOLYPUN [OL YVSL VM TP9 group investigates host-parasite HќLJ[Z IHJ[LYPHS HKOLZPVU [V O\THU provides a better understanding of the conventional culture, most frequently in Echinococcus multilocularis early UHZVWOHY`UNLHSLWP[OLSPHSJLSSZ KL]LSVWTLU[PU]P[YV interaction mechanisms and parasite HIGHLIGHTS & OUTLOOK RNA Biology 16(4):390-396 genetic basis of their pathogenicity. Streptococcus pneumoniae (41%), PLoS Neglected Tropical Diseases development using the cestode model Accordingly, as an academic :[YLW[VJVJJ\Z W`VNLULZ (19%), and 13:e0007932 system Echinococcus multilocularis. The group has developed numerous Liese JG, Schoen C, van der Linden M, diagnostic laboratory, we provide Staphylococcus aureus. Incidence of Lehmann L, Goettler D, Keller S, Maier The metacestode larval stage of this tools for studying molecular host- molecular diagnostic services in S. pneumoniae PPE/PE decreased Herz M and Brehm K (2019) ,]PKLUJL A, Segerer F, Rose MA, Streng A (2019) MVY KLUZV]PY\Z PU[LNYH[PVUZ PU[V [HWL tapeworm causes the lethal disease parasite interactions and parasite *OHUNLZPU[OLPUJPKLUJLHUKIHJ[LYPHS numerous collaborative research from 3.5 (95%CI 2.5-4.6) per million ^VYTNLUVTLZ alveolar echinococcosis (AE) through development, including in-vitro HL[PVSVN` VM WHLKPH[YPJ WHYHWUL\TVUPJ WYVQLJ[Z ^P[O ZJPLU[PÄJ HZ ^LSS HZ children in 2010/11 to 1.5 (95%CI 0.9- Parasites & Vectors 12(1):560 extensive cancer-like growth within the cultivation systems for Echinococcus WSL\YHSLќ\ZPVUZLTW`LTHPU.LYTHU` clinical partners within the ZINF and 2.4) in 2013/14 (p 0.002), followed ! H UH[PVU^PKL Z\Y]LPSSHUJL host liver, accompanied by suppression larvae and stem cells. Furthermore, Z[\K` beyond. We further use genomics by a re-increase to 2.2 (95%CI 1.5- Förster S, Koziol U, Schäfer T, Duvoisin of the host immune system. AE the group completed a whole genome/ Clinical Microbiology and Infection and transcriptomics to understand 3.2) by 2016/17 (p 0.205). These R, Cailliau K, Vanderstraete M, Dissous 25(7):857-864 C, Brehm K (2019) ;OLYVSLVMÄIYVISHZ[ treatment causes enormous problems transcriptome sequencing project for the genomic basis for commensal and data show that cases of pediatric NYV^[OMHJ[VYZPNUHSSPUNPU,JOPUVJVJJ\Z since only few cases are amenable to E. multilocularis. Recently, the group invasive behavior in human-adapted PPE/PE were still caused mainly by T\S[PSVJ\SHYPZ KL]LSVWTLU[ HUK OVZ[ surgical treatment and the majority discovered molecular developmental Heidrich N, Bauriedl AS, Barquist L, pathogens. S. pneumoniae despite widespread parasite interaction. Li L, Schoen C*, Vogel J* (2017) ;OL PLoS Neglected Tropical Diseases of patients have to undergo life-long mechanisms explaining cancer-like WYPTHY` [YHUZJYPW[VTL VM 5LPZZLYPH PCV immunization and, increasingly, 13(3):e0006959 chemotherapy. The group previously growth behavior of the E. multilocularis TLUPUNP[PKPZHUKP[ZPU[LYHJ[PVU^P[O[OL also by :W`VNLULZ showed that parasite growth is metacestode, which is achieved by 95(JOHWLYVUL/MX Nucleic Acids Research 45(10):6147- HIGHLIGHTS & OUTLOOK Montagne J, Preza M, Castillo E, decisively driven by totipotent somatic modulation of the anterior-posterior 67 5LPZZLYPH TLUPUNP[PKPZ is a prime Brehm K, Koziol U (2019) +P]LYNLU[ stem cells, and the proliferation body axis of the invading larvae. 7HYHWUL\TVUPJ WSL\YHS Lќ\ZPVUZ example of another human-adapted (_PUHUK.:2WHYHSVNZPU[OLIL[H JH[LUPU KLZ[Y\J[PVU JVTWSL_LZ VM dynamics of this cell population is at This is (1) controlled by parasite Harrison, O. B., Schoen C, Retchless empyema (PPE/PE) are severe commensal pathogen, which is tapeworms. the focus of our research interests. >U[ ZPNUHSPUN I\[  HSZV TVKPÄLK AC, Wang X, Jolley KA, Bray JE, Maiden complications of community-acquired the leading cause of sepsis and Development Genes and Evolution The group also extensively studies by host hormones and cytokines MCJ (2017) 5LPZZLYPH NLUVTPJZ! pneumonia. In collaboration with the epidemic meningitis worldwide. In 229(4):89-102 J\YYLU[Z[H[\ZHUKM\[\YLWLYZWLJ[P]LZ parasite genomics/transcriptomics such as insulin, FGF, and EGF. Very Pathogens and Diseases 75(6):ftx060 Department of Pediatrics, University a previous genome-wide study, we and engages in the development recently, the group established that Hospital of Würzburg, we investigated found an association of its type II-C of forward genetic methodology the parasite stem cell population the bacterial etiology and incidence CRISPR/Cas system with carriage MVY ÅH[^VYT WHYHZP[LZ -PUHSS` is inherently resistant to currently of pediatric PPE/PE in Germany and thus, less invasive lineages. immune-modulatory activities of used chemotherapeutics (LN after the introduction of universal We further showed that cas9 benzimidazoles) and that secreted deletion strains are impaired in the parasite cytokines of the TGF-b family adhesion to human nasopharyngeal actively induce immunosuppressive cells, which constitutes a central T-cells during an infection. These data step in the pathogenesis of L_WSHPUMVY[OLÄYZ[[PTL^O`J\YYLU[ invasive meningococcal disease. AE chemotherapy is parasitostatic Transcriptome sequencing and RIP- only, and how immunosuppression of seq analyses performed in close the host is achieved. collaboration with the group of Prof. Dr. Jörg Vogel (IMIB/HIRI) further Ongoing studies focus on the showed that meningococcal Cas9 establishment of transgene tech- KVLZUV[KPYLJ[S`IPUK[VVYHќLJ[[OL niques in the parasite (LN by expression of surface adhesins but *90:79*HZ  VU [OL PUÅ\LUJL VM YH[OLYL_LY[ZP[ZLќLJ[VUJLSSHKOLZPVU the host immune response on body in an indirect manner. Consequently, H_PZ TVKPÄJH[PVU PU WHYHZP[L SHY]HL [OLZL ÄUKPUNZ WYV]PKL ÄYZ[ L]PKLUJL and on the development of novel that the meningococcal CRISPR/Cas chemotherapeutics targeting the system exerts novel functions beyond WHYHZP[L»ZRPUVTL its established role in defense against foreign DNA. Whole mount in situ hybridization analysis of E. multilocularis FGF (Emfr2) expression in . Deletion of Cas9, RNase III (rnc), and tracrRNA, but not of CRISPR-RNAs impairs adhesion to human metacestode vesicles (A) with developing protoscoleces (B,C) and mature protoscolex (D). nasopharyngeal cells in vitro (Heidrich et al., 2019, Methods in Molecular Biology 1969:33-49).

48 49 3.2 INSTITUTE FOR HYGIENE AND MICROBIOLOGY

HOST-PATHOGEN INTERACTIONS INFECTION EPIDEMIOLOGY OF NEISSERIA MENINGITIDIS AND

PROF. ALEXANDRA SCHUBERT-UNKMEIR HOSPITAL INFECTION CONTROL Institute for Hygiene and Microbiology PROF. ULRICH VOGEL [email protected] I +49 931 31 46721 Institute for Hygiene and Microbiology www.hygiene.uni-wuerzburg.de [email protected] I +49 931 31 46802 www.hygiene.uni-wuerzburg.de

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK RESEARCH INTERESTS of sterilization on bioink components SELECTED PUBLICATIONS SELECTED PUBLICATIONS in collaboration with the Chair for Drug Martins Gomes SF, Westermann AJ, The group is interested in under- Based on our initial observation, we Krone M, Lâm TT, Claus H, Vogel U 5LPZZLYPH TLUPUNP[PKPZ as well as Formulation and Delivery. Sauerwein T, Hertlein T, Förstner KU, standing the strategies used by have begun an in-depth analysis of (2020) 9LJ\YYLU[PU]HZP]LTLUPUNVJVJJHS /HLTVWOPS\ZPUÅ\LUaHL are commen- Ohlsen K, Metzger M, Shusta EV, 5LPZZLYPH TLUPUNP[PKPZ to colonize the role of the ASM-ceramide system PUMLJ[PVUZX\HU[PM`PUN[OLYPZR.LYTHU` sal pathogens of the human host. The reference laboratory since Kim BJ, Appelt-Menzel A, Schubert- the brain vasculature and to cross and involved signaling pathways. [V  The group conducts infection 2019 types all strains by genome- Unkmeir A (2019) 0UK\JLK7S\YPWV[LU[ Eurosurveillance 25 :[LT *LSS+LYP]LK )YHPU ,UKV[OLSPHS [OL ISVVKJLYLIYVZWPUHS Å\PK IHYYPLY During the last two years, we have epidemiology projects within the based methods in collaboration with *LSSZ HZ H *LSS\SHY 4VKLS [V :[\K` (B-CSFB). To reveal these strategies, shown that the interaction of the type Krone M, Lâm TT, Vogel U, Claus H framework of the National Reference the Core Unit Systems Medicine. 5LPZZLYPHTLUPUNP[PKPZ0UMLJ[PVU we use tissue culture-based cell IV pili of 5TLUPUNP[PKPZ with BECs (2020) :\ZJLW[PIPSP[`VMPU]HZP]L5LPZZLYPH Laboratory for meningococci and *S\Z[LY HSNVYP[OTZ ^PSS IL YLÄULK I` Frontiers in Microbiology 10:1181 models including brain endothelial contributes to a transient activation of TLUPUNP[PKPZ Z[YHPUZ PZVSH[LK PU .LYTHU` /HLTVWOPS\ZPUÅ\LUaHL (NRZMHi). reevaluating previously described [V HaP[OYVT`JPU HU HS[LYUH[P]L HNLU[ MVY Peters S, Schlegel J, Becam J, Avota E, cells (BECs) and a wide spectrum of ASM followed by ceramide release in post-exposure prophylaxis. outbreaks. A new database released Sauer M, Schubert-Unkmeir A (2019) innovative molecular, biochemical, BECs. By using KSTORM (with Prof. Journal of Antimicrobial Chemo- The infection control team of the by our group will be further developed. 5LPZZLYPHTLUPUNP[PKPZ;`WL0=7PSP;YPNNLY and cell biological methods. Dr. M. Sauer, Biocenter Würzburg), therapy 75(4):984-987 University Hospital in Würzburg led It will support data exchange with the 2+ Ca +LWLUKLU[ 3`ZVZVTHS ;YHѝJRPUN we showed that exposure of pilus- by Prof. Ulrich Vogel is involved in ECDC (Stockholm) and the PubMLST VM [OL (JPK :WOPUNVT`LSPUHZL ;V Preliminary data from our group enriched fractions to BECs increased Krone M, et al., Vogel U, Borrow R (2019) infection control projects. database (Oxford). ,UOHUJL:\YMHJL*LYHTPKL3L]LSZ 0UJYLHZL VM PU]HZP]L TLUPUNVJVJJHS Infection and Immunity 87(8):e00410-19 have revealed that 5TLUPUNP[PKPZ the overall number of CRPs with a size ZLYVNYV\W>KPZLHZLPU,\YVWL[V is capable of activating the enzyme of 80 nm in the plasma membrane.  The infection control team will focus its Schlegel J, Peters S, Doose S, acid sphingomyelinase (ASM) in Within the newly funded GRK 2581, we Eurosurveillance 24 HIGHLIGHTS & OUTLOOK ZJPLU[PÄJHJ[P]P[`VU[OLTHUHNLTLU[ Schubert-Unkmeir A, Sauer M (2019) :\WLY9LZVS\[PVU 4PJYVZJVW` BECs to modulate ASM-generated aim to analyze the role of sphingosine of COVID-19 in hospitals, utilizing ceramide levels in the membrane of 1 phosphate (S1P) and S1P1-2 during Moremi N, Claus H, Rutta L, Frosch In collaboration with various partners, KH[H HJJ\T\SH[LK K\YPUN [OL ÄYZ[ 9L]LHSZ3VJHS(JJ\T\SH[PVUVM7SHZTH M, Vogel U, Mshana SE (2018) /PNO 4LTIYHUL .HUNSPVZPKLZ H[ 5LPZZLYPH ECs. Ceramide molecules associate [OL PUÅHTTH[VY` YLZWVUZL HUK [OL JHYYPHNLYH[LVML_[LUKLKZWLJ[Y\TIL[H the National Reference Laboratory wave of the pandemic. Manuscripts TLUPUNP[PKPZ0U]HZPVU:P[LZ into large-membrane platforms modulation of barrier permeability and SHJ[HTHZLWYVK\JPUN,U[LYVIHJ[LYPHJLHL for meningococci and /PUÅ\LUaHL are currently in preparation on patient Frontiers in Cell and Developmental (CRPs), which serve as platforms integrity. HTVUN WH[PLU[Z HKTP[[LK MVY Z\YNLY` PU published work on various aspects admission screening and outbreak Biology 7:194 ;HUaHUPHU OVZWP[HSZ ^P[O H SV^ YH[L VM for the concentration of signaling LUKVNLUV\ZZ\YNPJHSZP[LPUMLJ[PVUZ of diagnostics, spread of invasive control in a nursing home. Burgert A, Schlegel J, Becam J, Doose S, components, their assembly into We have also initiated a study to Journal of Hospital Infection 100(1):47- isolates, vaccines, and carriage. Bieberich E, Schubert-Unkmeir A, higher-order complexes, and the implement iPSC-derived BECs as a 53 Sauer M (2017) *OHYHJ[LYPaH[PVU VM transmission of signals across the novel cellular model for 5TLUPUNP[PKPZ Hospital infection control projects 7SHZTH 4LTIYHUL *LYHTPKLZ I` :\WLY9LZVS\[PVU4PJYVZJVW` plasma membrane. infection in close collaboration with focused on surveillance in Tanzania in Angewandte Chemie International Dr. A. Appelt-Menzel/PD Dr. M. Metzger collaboration with Nyambura Moremi. Edition 56(22):6131-6135 (LS TERM Würzburg) within the The infection control laboratory .92  ),*Z ^LYL KPќLYLU[PH[LK contributed to a paper on the impact from iPSCs according to previously described methods. 5TLUPUNP[PKPZ was found to directly disrupt the TJ proteins ZO-1, Occludin, and Claudin-5. In accordance with TJ loss, a sharp loss in TEER, and an increase in NaF permeability could be shown. Notably, bacterial transmigration correlated with junctional disruption. In addition, RNA-Seq data analyses of infected iPSC-BECs were established (with Jun. Prof. Dr. A. Westermann, IMIB/HIRI) providing expression data of 5TLUPUNP[PKPZ-responsive host genes. In the future, we will develop a multicellular in-vitro model of the B-CSFB and implement co-culture models of human primary meningeal cells and BECs as well as an in-vitro Confocal microscopy images of iPSC-BECs seeded onto ibidi slides infected with GFP-expressing circulatory 2D 5TLUPUNP[PKPZ-BEC Structure of the meningococcal laboratory surveillance database at the reference laboratory for 5LPZZLYPHTLUPUNP[PKPZ strain MC58. Image from Martins Gomes et al., 2019, Frontiers in Microbiology. interaction model. meningococci. Image by Markus Reinhardt.

50 51 3.3 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY – DEPARTMENT OF VIROLOGY

LARS DÖLKEN

FLORIAN ERHARD

JÜRGEN SCHNEIDER-SCHAULIES

SIBYLLE SCHNEIDER-SCHAULIES

The Institute for Virology and Immunobiology is part of the Medical Faculty at the University of Würzburg. Prof. Dr. Lars Dölken has held the Chair of Virology since 2015.

Virology-focused research at the Institute centers on analyzing the regulatory principles involved in viral replication and gene expression. In addition, researchers are investigating the pathogenesis of several viruses and are elucidating the molecular basis for the occurrence of resistance to antiviral compounds. Research is also being conducted into the development of viral vectors to be used for gene therapy. The Institute also provides virus diagnostics to the University Clinics.

Imagemagemagege: HilH dee MeM erkertrkerrkee t

52 53 3.3 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY – DEPARTMENT OF VIROLOGY

SYSTEMS BIOLOGY OF HERPESVIRUS COMPUTATIONAL SYSTEMS INFECTIONS VIROLOGY

PROF. LARS DÖLKEN JUN. PROF. FLORIAN ERHARD Chair of Virology, Institute for Virology and Immunobiology - Dept. of Virology Institute for Virology and Immunobiology - Dept. of Virology [email protected] I +49 931 31 88185 ñRULDQHUKDUG#XQLZXHU]EXUJGH, www.virologie.uni-wuerzburg.de/virologie www.virologie.uni-wuerzburg.de/virologie

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK RESEARCH INTERESTS analyze the temporal dynamics of RNA SELECTED PUBLICATIONS SELECTED PUBLICATIONS on a large-scale. We developed the Whisnant AW, Jürges CS, Hennig T, Herpesviruses cause a broad spec- Using an integrative multiomics Whisnant AW, Jürges CS, Hennig T, We develop computational and statis- ÄYZ[TL[OVK.9(5+:3(4[OH[JHU Wyler E, Prusty B, Rutkowski AJ, trum of diseases ranging from the HWWYVHJO ^L PKLU[PÄLK O\UKYLKZ VM Wyler E, Prusty B, Rutkowski AJ, tical methods and tools for analyzing compute truly quantitative temporal L‘hernault A, Djakovic L, Göbel M, common cold sore to cancer. Our novel viral transcripts and ORFs of L‘hernault A, Djakovic L, Göbel M, “omics” data. By applying these estimates from such experiments by Döring K, Menegatti J, Antrobus R, group employs systems biology HSV-1, HCMV, and MCMV. Many of Döring K, Menegatti J, Antrobus R, approaches in various herpesvirus statistical modeling. Together with Matheson NJ, Künzig FWH, Mastrobuoni Matheson NJ, Künzig FWH, Mastrobuoni G, Bielow C, Kempa S, Liang C, approaches combined with virus these represent so-called short ORFs G, Bielow C, Kempa S, Liang C, models we study the mechanisms by the Dölken and Saliba labs, we then Dandekar T, Zimmer R, Landthaler reverse genetics systems to study (sORFs). Large-scale validation of Dandekar T, Zimmer R, Landthaler which viruses take over or modulate developed single-cell SLAM-seq M, Grässer F, Lehner PJ, Friedel CC, viral host cell modulation and cellular sORFs was achieved by MHC-I M, Grässer F, Lehner PJ, Friedel CC, their host cells and evade immune (scSLAM-seq). In contrast to standard Erhard F*, Dölken L* (2020) 0U[LNYH[P]L Erhard F*, Dölken L* (2020) 0U[LNYH[P]L M\UJ[PVUHS NLUVTPJZ KLJVKLZ OLYWLZ immune evasion. Herpes simplex ligandome analyses. This revealed that M\UJ[PVUHS NLUVTPJZ KLJVKLZ OLYWLZ responses. Key technologies such scRNA-seq, this new technique ZPTWSL_]PY\Z virus 1 (HSV-1) is the causative sORFs encode a novel class of stress- ZPTWSL_]PY\Z as next generation sequencing and resolves fast, dynamic changes of Nature Communications 11(1):2038 agent of common cold sores but is responsive antigens, which represent Nature Communications 11(1):2038 THZZ ZWLJ[YVTL[Y` VќLY JV\U[SLZZ gene expression as LN induced by also responsible for life-threatening poor substrates for cross-presentation opportunities in systems biology. To virus infection with unprecedented Erhard F, Baptista MAP, Krammer T, encephalitis. During productive due to their inherent instability but Erhard F, Baptista MAP, Krammer T, take advantage of these, we work on detail in single cells and directly Hennig T, Lange M, Arampatzi P, Hennig T, Lange M, Arampatzi P, Jürges CS, Theis FJ, Saliba AE, infection, HSV-1 installs a profound HYL UL]LY[OLSLZZ LѝJPLU[S` WYLZLU[LK Jürges CS, Theis FJ, Saliba AE, innovative experimental approaches visualizes transcriptional bursting. By Dölken L (2019) ZJ:3(4ZLX YL]LHSZ ZO\[VќVMOVZ[NLULL_WYLZZPVU6\Y via MHC-I. In the frame of our DFG- Dölken L (2019) ZJ:3(4ZLX YL]LHSZ in collaboration with groups inside LќLJ[P]LS`TLHZ\YPUNL]LY`JLSSH[[^V JVYLMLH[\YLZVM[YHUZJYPW[PVUK`UHTPJZPU group studies the underlying molecular funded research unit FOR 2830, we JVYLMLH[\YLZVM[YHUZJYPW[PVUK`UHTPJZ and outside of the ZINF and combine time points, we can infer functional ZPUNSLJLSSZ PUZPUNSLJLSSZ Nature 571(7765):419-423. mechanisms. A second focus is on aim to elucidate the functional role of Nature 571(7765):419-423 [OLZL ^P[O ZWLJPÄJHSS` [HPSVYLK genetic interactions by modeling cytomegaloviruses (CMV). Human CMV uORFs in immunological control computational analysis methods. We transcriptional activity of individual cells Erhard F, Halenius A, Zimmermann CMV (HCMV) is an important pathogen and viral evasion thereof. Erhard F, Halenius A, Zimmermann also focus on the integrative analysis in response to a perturbation based * 3»/LYUH\S[ ( 2V^HSL^ZRP +1 in immunosuppressed patients and * 3»/LYUH\S[ ( 2V^HSL^ZRP +1 of “multi-omics” data. We believe on their pre-perturbation expression Weekes MP, Stevanovic S, Zimmer R, responsible for congenital infections Recently, we made the surprising Weekes MP, Stevanovic S, Zimmer R, that technological advances and heterogeneity. This approach, called Dölken L (2018) 0TWYV]LK 9PIVZLX Dölken L (2018) 0TWYV]LK 9PIVZLX LUHISLZPKLU[PÄJH[PVUVMJY`W[PJ[YHUZSH[PVU in about 1 of 1,000 newborns. The observation that HSV-1 triggers LUHISLZPKLU[PÄJH[PVUVMJY`W[PJ[YHUZSH[PVU integrative approaches will pave the Heterogeneity sequencing, will enable events. murine CMV (MCMV) animal model widespread disruption of transcription events. way towards understanding complex us to study pro- and antiviral factors Nature Methods 15(5):363-366 recapitulates many features of CMV termination of cellular but not Nature Methods 15(5):363-366 systems such as virus infection. for various viruses. biology. Our group studies the viral genes. In collaboration with Baptista MAP, Dölken L (2018) 95( function and immunological role of Yongsheng Shi from Irvine, USA, we Jürges C, Dölken L, Erhard F (2018) Based on our methods PRICE (high- K`UHTPJZ YL]LHSLK I` TL[HIVSPJ 95( +PZZLJ[PUN UL^S` [YHUZJYPILK HUK VSK SHILSPUN HUK IPVJOLTPJHS U\JSLVZPKL non-canonical CMV gene products found that the viral master regulator 95(\ZPUN.9(5+:3(4 HIGHLIGHTS & OUTLOOK resolution analysis of ribosome conversions. including upstream open reading ICP27 both disrupts cellular and Bioinformatics 34(13):i218-i226 WYVÄSPUN KH[H HUK 7LW[PKL790:4 Nature Methods 15(3):171-172 frames (uORFs) and microRNAs. rescues viral transcription termination Metabolic RNA labeling with nucleotide WYV[LVNLUVTPJ PKLU[PÄJH[PVU VM by interacting with the cellular CPSF conversion provides elegant means to MHC-I ligands), we uncovered cryptic complex. peptides, which are translated from mostly short and so far unknown In collaboration with Florian Erhard ORFs, and constitute up to 15% of the (Institute for Virology and Immuno- peptides presented by MHC-I. These biology) and Emmanuel Saliba are now tested immunologically (with (Helmholtz Institute for RNA-based the Schlosser and Schilling labs for Infection Research), we developed tumor peptides, and within FOR 2830 single cell SLAM-seq (scSLAM-seq). for viral peptides). Employing metabolic RNA labeling and chemical nucleotide conversions, Furthermore, we used a large collection [OPZ LUHISLZ [OL KPќLYLU[PH[PVU VM of omics data sets to compile and newly transcribed RNA from pre- validate the most comprehensive existing RNA in individual cells thereby annotation of a large DNA virus (herpes recording transcriptional activity for simplex virus 1; with the Dölken lab). A thousands of genes. scSLAM-seq similar annotation for the human and provides a temporal dimension to murine cytomegalovirus genomes is a ZPUNSL JLSS L_WYLZZPVU WYVÄSLZ HUK major goal of our FOR 2830 project. enables dose-response analysis at single cell level. (>VYRÅV^VMZJ:3(4ZLX),_HTWSLVM4*4=PUK\JLKNLULL_WYLZZPVU The conversion of 4sU incorporated into new RNA results in characteristic mismatches. New and old 95(JHUILX\HU[PÄLKPUZPUNSLJLSSZMVY[OV\ZHUKZVMNLULZ

54 55 3.3 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY – DEPARTMENT OF VIROLOGY

MORBILLIVIRUS PATHOGENESIS VIRAL IMMUNOMODULATION

PROF. JÜRGEN SCHNEIDER-SCHAULIES PROF. SIBYLLE SCHNEIDER-SCHAULIES Institute for Virology and Immunobiology - Dept. of Virology Institute for Virology and Immunobiology - Dept. of Virology [email protected] I +49 931 31 81564 [email protected] I +49 931 31 81566 www.virologie.uni-wuerzburg.de/virologie www.virologie.uni-wuerzburg.de/virologie

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK RESEARCH INTERESTS micro-domains and thereby, cellular SELECTED PUBLICATIONS SELECTED PUBLICATIONS signaling. MV interaction with T cells Grafen A, Schumacher F, Chithelen J, Measles, caused by a negative- We are using cultures of primary Derakhshani S, Kurz A, Japtok L, Viruses can modulate the activity of induced neutral sphingomyelinase Kleuser B, Beyersdorf N, Schneider- stranded RNA virus of the genus human peripheral blood mononuclear Schumacher F, Pilgram L, Steinke M, host immune cells to facilitate their (NSM) activity, and this essentially Schaulies J (2019)

Current and future experiments MVJ\Z VU [OL PKLU[PÄJH[PVU HUK functional characterization of up- and KV^UZ[YLHT LќLJ[VYZ PU 4=PUK\JLK NSM2 activation as well as their spatiotemporal regulation. These are being performed in collaboration with partnering groups within the GRK 2581 (granted early in 2020) and involve systems biology, signaling, biochemical, and high resolution.

Increase of S1P concentrations in primary human PBMCs after infection with MV and inhibition of this by (A) MV infected (GFP+) DCs switch to fast, ameboid migration in a 3D respiratory tract model, and SKI-II, but not by ceranib-2. Grafen et al., 2019, Frontiers in Cell and Developmental Biology. transmit MV to endo- and epithelial cells (B).

56 57 3.4 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY – DEPARTMENT OF IMMUNOLOGY

WOLFGANG KASTENMÜLLER

NIKLAS BEYERSDORF

THOMAS HERRMANN

MANFRED LUTZ

The Institute for Virology and Immunobiology is part of the Medical Faculty at the University of Würzburg. Prof. Dr. Wolfgang Kastenmüller is the Acting Director of the Department of Immunology.

The research interests of the individual groups focus on a broad spectrum of basic and applied immunological topics. Many of the results from basic research are translated into preclinical therapy models for infections, allergies, autoimmune diseases, transplant rejection, and graft-versus-host disease. The Institute also provides diagnostic services for autoantibodies for the University Clinics.

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58 59 3.4 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY – DEPARTMENT OF IMMUNOLOGY

LEUKOCYTE DYNAMICS T CELL BIOLOGY

PROF. WOLFGANG KASTENMÜLLER DR. NIKLAS BEYERSDORF Chair of Immunology, Institute for Virology and Immunobiology Institute for Virology and Immunobiology - Dept. of Immunology Chair of Systems Immunology I, Institute of Systems Immunology [email protected] I +49 931 31 81527 [email protected] I +49 931 31 81816 www.virologie.uni-wuerzburg.de/immunologie www.med.uni-wuerzburg.de/systemimmunologie

RESEARCH INTERESTS T cells and studying their ability to RESEARCH INTERESTS 1 YNLU :JOULPKLY:JOH\SPLZ» HUK SELECTED PUBLICATIONS protect the host against bacterial SELECTED PUBLICATIONS our group could, however, recently Ataide MA, Komander K, Knöpper K, A central aspect of the cellular ele- infections such as Staphylococcus Grafen A, Schumacher F, Chithelen J, Innate and adaptive immunity interact show that modulators of sphingolipid 7L[LYZ(,>\/,PJROVќ:.VNPZO]PSP ments of the immune system is their aureus. Kleuser B, Beyersdorf N, Schneider- to provide the host with a highly metabolism are capable of inhibiting T, Weber J, Grafen A, Kallies A, Garbi capacity to rapidly migrate between Schaulies J (2019) LSa 4 ,PJROVќ : (IK\SSHO A Trebicka J, Gartlan KH, Spicer JA, HU LќLJ[P]L PTT\UL YLZWVUZL -VY transcription factor BATF3 regulates Dasari P, Koleci N, Shopova IA, pathogens, T cells also play an other viral infections, of the brain. Demetris AJ, Akhlaghi H, Anton M, example, they aim to understand the quality of memory CD8 T cells in Wartenberg D, Beyersdorf N, Dietrich S, PTWVY[HU[ YVSL PU ÄNO[PUN JHUJLY Manske K, Zehn D, Nieswandt B, how, when, and where CD8 T cells a cell intrinsic manner in the context Sahagún-Ruiz A, Figge MT, Skerka Therefore, our group has a long- After an acute viral or bacterial Kurts C, Trapani JA, Knolle P, are activated and with which dendritic of infections. In contrast to known C, Brakhage AA, Zipfel PF (2019) standing interest in cell surface infection, immunological memory Wohlleber D, Kastenmüller W (2018) ,UVSHZL -YVT (ZWLYNPSS\Z M\TPNH[\Z 7LYMVYPU PUOPIP[PVU WYV[LJ[Z MYVT SL[OHS cell types they communicate in order factors involved in CD8 T cell memory 0Z H 4VVUSPNO[PUN 7YV[LPU ;OH[ )PUKZ receptor-mediated T cell activation and arises protecting the host upon re- LUKV[OLSPHS KHTHNL K\YPUN M\STPUHU[ to generate an adaptive immune formation such as TCF7, BATF3 is the Human Plasma Complement how T cell responses can be har- infection with the same pathogen. viral hepatitis. response in the context of an acute or only transiently expressed after T cell 7YV[LPUZ -HJ[VY / -/3 *)7HUK nessed for therapeutic purposes. In the protection against intracellular Nature Communications 9(1):4805 7SHZTPUVNLU chronic viral infection. They use these HJ[P]H[PVUI\[OHZSVUNSHZ[PUNLќLJ[Z Frontiers in Immunology 10:2573 pathogens, so-called CD4+ T helper 1 Bedoui S, Gebhardt T, Gasteiger G, insights to improve immunotherapy on T cell survival and persistence. In (Th1) cells producing the cytokine Kastenmüller W (2016) Parallels and to engineer T cells to optimize [OPZ YLNHYK [OL LќLJ[Z VM )(;- HYL Langenhorst D, Haack S, Göb S, HIGHLIGHTS & OUTLOOK PU[LYMLYVU ф 0-5 ф HYL RL` P[O AWARDS protective immune response, we we are particularly excited about the Unfortunately, in some children the our recent observation that secondary Schneider-Schaulies J, Beyersdorf N ERC Consolidator Grant on the topic: are also interested to investigate the LќLJ[Z VM )(;- V]LYL_WYLZZPVU PU measles virus persists in the brain after stimulation of Th1 cells heavily de- dynamic behavior and interaction CD8 T cells, because it enhances (2018) *+-V_WYLN\SH[VY`;JLSS the acute infection, which may lead pends on co-stimulation via the CD28 :WH[PV[LTWVYHS YLN\SH[PVU VM ;JLSS TLKPH[LK PTT\UVTVK\SH[PVU I` HU[P 7YPTPUN (2018) of cells that regulate immunity like JLSS\SHY Ä[ULZZ HUK SVUNL]P[` ^P[OV\[ KLWYLZZHU[Z PUOPIP[PUN HJPK ZWOPUNV to a lethal form of encephalitis called receptor on the T cell surface, we Treg cells. More recently, we are HќLJ[PUN *+  ; JLSS KPќLYLU[PH[PVU myelinase. Subacute Sclerosing Panencephalitis JV\SK ZOV^ [OH[ ZLUZPUN ºKHUNLY» PZ investigating the function and mig- or functionality. BATF3 does so by Biological Chemistry 399(10):1175-82 (SSPE), for which there currently essential for their re-activation. The ratory behavior of so-called invariant optimizing CD8 T cell metabolism and is no curative treatments. Prof. continued dependence of Th1 cells the expression patterns of cytokine on CD28 co-stimulation reduces the and costimulatory receptors. Due to risk of unwanted immune responses these changes, BATF3 overexpressing and opens novel possibilities for CD8 T cells outcompeted control immunomodulatory interventions. populations in the context of acute and chronic viral infections. We further demonstrate that BATF3 optimizes CD8 T cell stemness and longevity not only in murine, but importantly also in human, CD8 T cells. Therefore, our results identify the AP-1 transcription factor family member BATF3 as a promising candidate to optimize the T cell quality for immunotherapy against cancer in humans.

The AP-1 family transcription factor BATF3 programs CD8 T cell memory. 0-5фZLJYL[PVUI`6=(ZWLJPÄJ*+;OLSWLY;OJLSSZNYL`PZYLK\JLK\WVU*+ PUOPIP[PVU (white). Published in Langenhorst et al., 2018, Frontiers in Immunology.

60 61 3.4 INSTITUTE FOR VIROLOGY AND IMMUNOBIOLOGY – DEPARTMENT OF IMMUNOLOGY

IMMUNOGENETICS IMMUNE REGULATION

PROF. THOMAS HERRMANN PROF. MANFRED LUTZ Institute for Virology and Immunobiology - Dept. of Immunology Institute for Virology and Immunobiology - Dept. of Immunology [email protected] I +49 931 31 81538 [email protected] I +49 931 31 81553 www.virologie.uni-wuerzburg.de/immunologie www.virologie.uni-wuerzburg.de/immunologie

RESEARCH INTERESTS family (LN CD80/86). Binding of PAgs RESEARCH INTERESTS As the interaction of MDSCs with SELECTED PUBLICATIONS to the intracellular B30.2 domain of SELECTED PUBLICATIONS mycobacteria is not well studied, Fichtner AS, Karunakaran MM, Gu S, =ф =х;JLSSZHYLLќLJ[VYZ^P[OHU[P BTN3A1 leads to a conformational John V, Kotze LA, Ribechini E, Walzl G, Infective microbes have developed we investigated the uptake, sig- Boughter CT, Borowska MT, Starick L, microbial and anti-tumor activity. Their change of the entire molecule, and Du Plessis N, Lutz MB (2019) *H]LVSPU a number of strategies to avoid naling, and suppressor function of Nohren A, Gobel TW, Adams EJ, LWVU`TV\Z =ф =х ;JLSS HU[PNLU ÄUHSS` [V =ф =х ;JLSS HJ[P]H[PVU I` *VU[YVSZ=LZPJ\SHY;39,_WYLZZPVUW  LSPTPUH[PVU I` [OL OVZ[»Z PTT\UL live Mycobacterium bovis Bacille- Herrmann T (2020) (SWHJH =PJ\NUH receptor recognizes phosphoantigens the BTN3A1-expressing cell. This :PNUHSPUNHUK;*LSS:\WWYLZZPVUPU)*. system such as activation of immune Calmette-Guérin (BCG) in murine WHJVZ [OL ÄYZ[ UVUWYPTH[L ZWLJPLZ 0UMLJ[LK 4\YPUL 4VUVJ`[PJ 4`LSVPK ^P[OHWOVZWOVHU[PNLUYLHJ[P]L=ф =х (PAg) sensing tumor or host cells. requires cooperation with the BTN3A1 +LYP]LK:\WWYLZZVY*LSSZ tolerance mechanisms. We are inves- 4+:*Z HUK [OL ZWLJPÄJ YVSL VM ;JLSSZ\IZL[ The PAg (E)-4-hydroxy-3-methyl-but- paralogues BTN3A2 and BTN3A3. Frontiers in Immunology 10:2826 [PNH[PUN OV^ KPќLYLU[ WH[OVNLUZ caveolin-1 (Cav-1) in this process. PNAS 117(12):6697-6707 2-enyl pyrophosphate (HMBPP) is L PKLU[PÄLK Ribechini E, Eckert I, Beilhack A, Du myeloid-derived suppressor cells receptors-2 and -4 (TLR2, TLR4) Karunakaran MM, Willcox CR, Salim M, Plessis N, Walzl G, Schleicher U, Paletta D, Fichtner AS, Noll A, Starick L, apicomplexa such as 7SHZTVKP\T and characterized key genes of PAg- Ritter U, Lutz MB (2019) /LH[RPSSLK (MDSCs). that are important for mycobacterial Nöhren A, Begley CR, Berwick KA, ZWWHUKSLHKZ[VL_WHUZPVUVM=ф =х YLJVNUP[PVU=ф =хHUK);5HUK Mycobacterium tuberculosis prime-boost YLJVNUP[PVU L HSZV PKLU[PÄLK [OL O\THU requirements for the conversion 0U[OLZLHYJOMVYHULѝJPLU[[\ILYJ\ >P[ULZZI\[5V[H-\UJ[PVUHS,_HTWSL AWARDS MVY[OL,TLYNLUJLVM[OL)\[`YVWOPSPU BTN2A1 molecule as a new player of human or mouse conventional losis (TB) vaccine, we had previously =ф =х:`Z[LTPU7SHJLU[HS4HTTHSZ in PAg-presentation by screening Research Grant and Award of the monocytes into monocytic MDSCs. found that TB patients show elevated Frontiers in Immunology 9:265 HIGHLIGHTS & OUTLOOK human-rodent radiation hybrids for Vogel-Stiftung Dr. Eckernkamp (2019) ;OPZPUKPJH[LZ[OH[PUZ[LHKVMHZWLJPÄJ levels of MDSCs in their blood their capacity of PAg-presentation MDSC precursor, transcriptional and circulation and thus hypothesized (RL`WSH`LYPU=ф =х;JLSSHJ[P]H[PVU (Karunakaran et al., 2020). In translational changes induced in that mycobacterial vaccines may is the cell surface molecule butyrophilin cooperation with the Willcox group TVUVJ`[LZ HYL Z\ѝJPLU[ [V NLULYH[L also induce MDSCs that counteract BTN3A1. Its extracellular domain is in Birmingham, UK, BTN2A1 binding monocytic MDSCs. the vaccine-induced T cell immune very similar to members of the B7 ^HZZOV^U[V[OL=ф NLULWYVK\J[ response. Our data indicate and the V-domain of BTN3A1. that repeated vaccination with BTN2A1 and BTN3A1 transferred the Mycobacterium tuberculosis (Mtb) capacity of PAg presentation to rodent LT\SZPÄLK PU VPS *VTWSL[L -YL\UKºZ cells and is aimed to be used for Adjuvant) induces MDSCs. As a creation of a transgenic mouse model novel mechanism of suppression, we MVY7(NYLHJ[P]L=ф =х;JLSSZ^OPJO PKLU[PÄLK [OL RPSSPUN VM +*Z PU [OL so far can only be studied in primates. spleen that indirectly suppresses T cell The study of the molecular basis of responses against Mtb (see Figure). interaction between the butyrophilins HUKVMSPNHUKZIPUKPUN[V[OL=ф =х We will further investigate the inter- TCR will also be continued. action of mycobacteria with MDSCs and their induction by anti-TB vaccines. We will also study the detailed interaction of MDSCs with T cells by testing new MDSC markers for functional suppressor activity as well as their in-vivo homing potential to understand the anatomical strategy of MDSC-mediated immune =ф =х;JLSSHJ[P]H[PVU!);5(IPUKZ[V=ф HUK7(NIPUKPUN[V);5(PUK\JLZHJVUMVYTH[PVUVM[OL Repeated Mycobacterium tuberculosis (Mtb) vaccinations (CFA) induce myeloid-derived suppressor suppression in whole organisms. );5JVTWSL_L_WVZPUNHU\URUV^USPNHUKZ[V[OL*+9ZVM=ф =х;*9/LYTHUUet al., 2020, Cells. cells (MDSC) that suppress T cell responses by killing dendritic cells (DC).

62 63 3.5 DEPARTMENT OF MICROBIOLOGY, THEODOR BOVERI INSTITUTE, BIOCENTER

THOMAS RUDEL

MARTIN FRAUNHOLZ

ROY GROSS

VERA KOZJAK-PAVLOVIC

The Department of Microbiology is part of the Faculty of Biology at the University of Würzburg. Prof. Dr. Thomas Rudel has chaired the department since 2008.

The research activities at the Department center on the pathogenicity TLJOHUPZTZVMKPќLYLU[TPJYVVYNHUPZTZPUJS\KPUN[OLTHUPW\SH[PVUVM]HYPV\Z signaling cascades, non-coding RNAs, and cellular processes such as the cell death pathways in the host. In this context, infection biology of obligate intracellular bacteria such as *OSHT`KPH spp. is a major focus. Groups are also investigating the molecular basis of disseminating gonococcal infections and the host cell death induced by Staphylococcus aureus, as well as the intracellular lifestyle of this bacterium. In addition, there is also great interest in understanding the role of (co-)infections in the onset of ovarian cancer and the signaling pathways involved, as well as the development and application of new 3D infection models.

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64 65 3.5 DEPARTMENT OF MICROBIOLOGY, THEODOR BOVERI INSTITUTE, BIOCENTER

INFECTION BIOLOGY OF BACTERIA CELLULAR MICROBIOLOGY

PROF. THOMAS RUDEL DR. MARTIN FRAUNHOLZ Chair of Microbiology Department of Microbiology, Theodor Boveri Institute, Biocenter Department of Microbiology, Theodor Boveri Institute, Biocenter [email protected] I +49 931 31 83242 [email protected] I +49 931 31 84401 www.biozentrum.uni-wuerzburg.de/mikrobio www.biozentrum.uni-wuerzburg.de/mikrobio

RESEARCH INTERESTS major cause of sexually transmitted RESEARCH INTERESTS involved in the process. The S. aureus SELECTED PUBLICATIONS diseases. Infections often occur SELECTED PUBLICATIONS NRPS and its cyclized dipeptide Rajeeve K, Das S, Prusty BK, Rudel T The group investigates pathogenicity without symptoms, a feature that Horn J, Klepsch M, Manger M, Wolz C, Staphylococcus aureus is taken up by products enhance S. aureus phago- (2018) *OSHT`KPH [YHJOVTH[PZ WHYH mechanisms of the major human has been attributed to the ability Rudel T, Fraunholz M (2018) Long phagocytic cells of the human immune somal escape, thereby contributing to S`ZLZ UL\[YVWOPSZ [V L]HKL [OL OVZ[ pathogens *OSHT`KPH, 5LPZZLYPH of the pathogen to evade the host 5VUJVKPUN 95( ::9 *VU[YVSZ system but is also readily internalized epithelial and immune cell death. innate immune response. NVUVYYOVLHL, and Staphylococcus immune response. We could show :[HWO`SVJVJJ\Z H\YL\Z (SWOH;V_PU by cells such as endothelial or epithelial Nature Microbiology 3(7):824-835 ;YHUZJYPW[PVU PU 9LZWVUZL [V ,U]PYVU aureus. Furthermore, there is a focus that C. trachomatis paralyses the mental Stimuli. cells. Cytotoxic S. aureus strains are To identify virulence factors involved Chowdhury SR, Reimer A, Sharan M, on bacterial and viral co-infections and host immune system by preventing Journal of Bacteriology 200(22): able to escape phagosomal vesicles, in S. aureus-induced virulence on a Kozjak-Pavlovic V, Eulalio A, Prusty BK, their impact on human diseases such the activation of polymorphic nuclear e00252 replicate in the cytoplasm, and kill the genome-wide scale, we conducted Fraunholz M, Karunakaran K, Rudel T as cancer. leukocytes (PMNs). PMNs infected host cells from within. The involved unbiased transposon mutant pool (2017) *OSHT`KPH WYLZLY]LZ [OL Das S, Lindemann C, Young BC, Muller J, TP[VJOVUKYPHS UL[^VYR ULJLZZHY` MVY with *OSHT`KPH fail to produce Österreich B, Ternette N, Winkler AC, IHJ[LYPHS LќLJ[VYZ HUK OVZ[ MHJ[VYZ screens in vitro and in vivo. By YLWSPJH[PVU ]PH TPJYV95(KLWLUKLU[ During infection, bacterial pathogens neutrophil extracellular traps and the Paprotka K, Reinhardt R, Förstner KU, as well as the underlying molecular transposon insertion site deep PUOPIP[PVUVMÄZZPVU can dramatically alter host cell function bacteria are able to survive in PMNs Allen E, Flaxman A, Yamaguchi Y, mechanisms are largely unknown. ZLX\LUJPUN ^L UV[ VUS` PKLU[PÄLK Journal of Cell Biology 216(4):1071- to overcome innate and acquired for extended periods of time. We have Rollier CS, van Diemen P, Blättner S, a role for the NRPS in S. aureus 1089 Remmele CW, Selle M, Dittrich M, immune responses and to inhabit their PKLU[PÄLK [OL ZLJYL[LK JOSHT`KPHS Mueller T, Vogel J, Ohlsen K, Crook DW, The research group focuses on the PUMLJ[PVUZ I\[ HSZV PKLU[PÄLK [OL Fischer A, Harrison KS, Ramirez Y, preferred niches. Research is divided -like activating factor (CPAF) Massey R, Wilson DJ, Rudel R, PKLU[PÄJH[PVU VM IHJ[LYPHS ]PY\SLUJL involvement of the transcriptional Auer D, Chowdhury SR, Prusty BK, into three major areas: (1) infection HZ HU LќLJ[VY TLKPH[PUN [OL L]HZPVU Wyllie DH, Fraunholz M (2016) factors involved in phagosomal es- regulator Rsp in S. aureus intracellular Sauer F, Dimond Z, Kisker C, Scott biology of obligate intracellular bacteria of the innate immune response since 5H[\YHST\[H[PVUZPUH:[HWO`SVJVJJ\Z cape and cytotoxicity as well as host cytotoxicity. Mutants in rsp had Hefty P, Rudel T (2017) *OSHT`KPH H\YL\Z ]PY\SLUJL YLN\SH[VY H[[LU\H[L [YHJOVTH[PZJVU[HPUPUN ]HJ\VSL ZLY]LZ (*OSHT`KPH :PTRHUPH), (2) bacterial *7(-KLÄJPLU[ *OSHT`KPH activate J`[V[V_PJP[`I\[WLYTP[IHJ[LYLTPHHUK factors that support the intracellular reduced cytotoxicity and were HZKL\IPX\P[PUH[PVUWSH[MVYT[VZ[HIPSPaL factors required for dissemination and 745ZHUKHYLZ\IZLX\LU[S`LѝJPLU[S` HIZJLZZMVYTH[PVU survival of S. aureus. avirulent in mouse lung infections. 4JSHUK[VPU[LYMLYL^P[OOVZ[KLMLUZL adaptation as well as the host cell killed. CPAF suppresses the oxidative PNAS 113(22):E3101-10 0KLU[PÄJH[PVU VM [OL [YHUZJYPW[PVU eLife 6:e21465 response to 5LPZZLYPH NVUVYYOVLHL, burst and interferes with chemical- factor regulon established the long Blättner S, Das S, Paprotka K, Eilers U, and (3) cell biology of Staphylococcus mediated activation of neutrophils. Krischke M, Kretschmer D, Remmele HIGHLIGHTS & OUTLOOK non-coding RNA SSR42 as the main AWARDS aureus infection, particularly the in- >LPKLU[PÄLKMVYT`SWLW[PKLYLJLW[VY CW, Dittrich M, Müller T, Schuelein-Voelk 9ZWLќLJ[VY4\[HU[Z^P[OPU[OLNLULZ duction of host cell death. 2 (FPR2) as a target of CPAF. FPR2 C, Hertlein T, Mueller MJ, Huettel B, )` PUMLJ[PUN Å\VYLZJLU[ WOHNVZVTHS for Rsp or SSR42 lost their hemolytic ERC Advanced Grant on the topic: Reinhardt R, Ohlsen K, Rudel T, 5L\[YVWOPS ¶ *OSHT`KPH 0U[LYHJ[PVUZ is cleaved by CPAF and released from Fraunholz M (2016) Staphylococcus escape reporter cell lines with and cytotoxic phenotypes. Most H[ [OL *YVZZYVHK VM (KHW[H[PVU HUK the surface of PMNs. H\YL\Z,_WSVP[ZH5VUYPIVZVTHS*`JSPJ S. aureus T\[HU[Z ^L PKLU[PÄLK interestingly, S. aureus rsp mutants +LMLUJL (2019) HIGHLIGHTS & OUTLOOK +PWLW[PKL [V 4VK\SH[L :\Y]P]HS ^P[OPU several bacterial genes involved in can be recovered from bacteremia We will continue to investigate ,WP[OLSPHS*LSSZHUK7OHNVJ`[LZ phagosomal escape of the pathogen. isolates in patients with nasal PLoS Pathogens 12(9):e1005857 *OSHT`KPH [YHJOVTH[PZ, an obligate various pathogenicity mechanisms (TVUN V[OLYZ ^L PKLU[PÄLK H UVU S. aureus carriage. This demonstrates intracellular human pathogen, is a VM KPќLYLU[ IHJ[LYPH >P[O YLZWLJ[ ribosomal peptide synthase (NRPS) that during human nasal carriage, to obligate intracellular bacteria, S. aureus is able to acquire mutations metabolic adaptation to the host cell within the rsp locus, which can intracellular environment will be of PUÅ\LUJL [OL PU]HZP]LULZZ VM [OL particular interest. Furthermore, we pathogen. will continue to pursue the molecular basis of disseminating gonococcal 6\YYLZ\S[ZPUKPJH[LHÄUL[\ULKOVZ[ infections and host cell death induced pathogen interplay for intracellular by S. aureus infection. In addition, it is S. aureus involving the uptake of the V\YNVHS[V\UKLYZ[HUK[OLZPNUPÄJHUJL bacteria, their host-cell dependent of infections in the emergence and phagosomal escape, growth within progression of cancer. Therefore, we the cells, and cytolysis of the infected aim to investigate the contribution host cells. We currently conduct time- of *OSHT`KPH infections to the onset resolved infection experiments to of ovarian cancer and the signaling characterize molecular mechanisms pathways involved using suitable in- and timing of the involved processes vitro and in-vivo models for malignant in both host and pathogen. transformation.

Co-infection of *OSHT`KPH wildtype (green, no ubiquitin) and a deubiquitinase mutant (strong ubi- ( Å\VYLZJLU[ LZJHWL YLWVY[LY NYLLU PZ YLJY\P[LK [V PU[YHJLSS\SHY S. aureus (red) upon phagosomal quitination of inclusion in pink) in the same host cell. escape of the bacteria. Scale bar: 5 μm.

66 67 3.5 DEPARTMENT OF MICROBIOLOGY, THEODOR BOVERI INSTITUTE, BIOCENTER

PERTUSSIS BACTERIAL INVASION AND INTRACELLULAR SURVIVAL

PROF. ROY GROSS DR. VERA KOZJAK-PAVLOVIC Department of Microbiology, Theodor Boveri Institute, Biocenter Department of Microbiology, Theodor Boveri Institute, Biocenter [email protected] I +49 931 31 84403 [email protected] I +49 931 31 88061 www.biozentrum.uni-wuerzburg.de/mikrobio www.biozentrum.uni-wuerzburg.de/mikrobio

RESEARCH INTERESTS to cause massive tissue destruction. RESEARCH INTERESTS depends on host cell lipids for SELECTED PUBLICATIONS Accordingly, we started to investigate SELECTED PUBLICATIONS development, which is why these Kupper M, Stigloher C, Feldhaar H, )VYKL[LSSH WLY[\ZZPZ is the obligate the activities of this toxin in human Kunz TC, Götz R, Gao S, Sauer M, We investigate bacterial and cellular bacteria are a good model for re- Gross R (2016) +PZ[YPI\[PVU VM [OL human pathogen that causes whoop- tissue model systems to further Kozjak-Pavlovic V (2020) L OH]L PKLU[PÄLK UV]LS JLSS\SHY Vecerek B (2015) ;YHUZJYPW[PVUHS reactogenic whole cell vaccines. Since the methods to reproducibly generate ;PZZ\L 4VKLS MVY 3VUN;LYT :[\K` VM pathogen :PTRHUPHULNL]LUZPZ. and bacterial factors important for WYVÄSPUNVM)VYKL[LSSHWLY[\ZZPZYL]LHSZ then, there has been the reemergence 3D tracheal models from primary 5LPZZLYPHNVUVYYOVLHL0UMLJ[PVU 5NVUVYYOVLHL attachment to, in- YLX\PYLTLU[VM95(JOHWLYVUL/MXMVY of pertussis even in countries with human cells were improved. The Frontiers in Microbiology 10:1740 5NVUVYYOVLHL is an obligate human vasion, and survival in epithelial cells ;`WL000ZLJYL[PVUZ`Z[LTM\UJ[PVUHSP[` good vaccination coverage. Thus, LќLJ[ZVMW\YPÄLK;*;VU[OLTVKLSZ pathogen that causes gonorrhea. and neutrophils. We have generated RNA Biology 12(2):175-85 Chowdhury SR, Reimer A, Sharan M, it is pertinent to characterize the was then investigated and compared Kozjak-Pavlovic V, Eulalio A, Prusty The bacteria depend on pili for initial 3D tissue models using endometrial, Gupta SK, Kupper M, Ratzka C, virulence mechanisms of this obligate with previously published results BK, Fraunholz M, Karunakaran K, adhesion, Opa proteins for invasion, mesothelial, colon, and urethral Feldhaar H, Vilcinskas A, Gross R, human pathogen in appropriate test mainly obtained in animal models. Rudel T (2017) *OSHT`KPH WYLZLY]LZ and PorB porin for dissemination. epithelial cell lines, and improved them Dandekar T, Förster F (2015) :JY\[PUPaPUN [OL TP[VJOVUKYPHS UL[^VYR ULJLZZHY` IA [OL PTT\UL KLMLUJL PU]LU[VY` VM systems most closely resembling the )YPLÅ` PU [OL + TVKLSZ [OL [V_PU MVYYLWSPJH[PVU]PHTPJYV95(KLWLUKLU[ 5L\[YVWOPSZ HYL [OL ÄYZ[ YLZWVUKLYZ by addition of endothelial cells and *HTWVUV[\Z ÅVYPKHU\Z HWWS`PUN [V[HS natural situation. For this purpose, we caused massive tissue destruction PUOPIP[PVUVMÄZZPVU during gonococcal infection. However, neutrophils. We established endo- [YHUZJYPW[VTLZLX\LUJPUN developed 3D tracheal models from including blebbing of epithelial cells. Journal of Cell Biology 216(4):1071- 5NVUVYYOVLHL can survive the metrial organoid culture as the source BMC Genomics 16(1):540 primary human cells (hTBMs) and use This phenomenon correlated with 1089 neutrophil attack, using them as a of primary cells. We also studied the these models to study and re-evaluate the induction of NO production and Trojan horse for spreading from the role of mitochondria during infection Steinke M, Gross R, Walles H, Reimer A, Seufert F, Weiwad M, Ebert Gangnus R, Schütze K, Walles T the relevance of B. pertussis virulence Z[PT\SH[PVUVMPUÅHTTH[VY`J`[VRPULZ J, Bzdyl NM, Kahler CM, Sarkar-Tyson primary infection site. with :ULNL]LUZPZ, which connected (2014) (U LUNPULLYLK + O\THU factors. These factors include several JVUÄYTPUN WYL]PV\Z YLZ\S[Z VI[HPULK M, Holzgrabe U, Rudel T, Kozjak- to our work on proteins crucial for HPY^H`T\JVZHTVKLSIHZLKVUHU:0: adhesins and toxins including the with hamster tracheal explants, Pavlovic V (2016) 0UOPIP[VYZ VM :ULNL]LUZPZ is a *OSHT`KPH-related mitochondrial morphology and cristae ZJHќVSK tracheal cytotoxin (TCT), which is a thus providing strong evidence THJYVWOHNL PUMLJ[P]P[` WV[LU[PH[VYSPRL obligate intracellular pathogen maintenance. Biomaterials 35(26):7355-62 770HZLZHќLJ[ULPZZLYPHSHUKJOSHT`KPHS spontaneously released low molecular for the importance of this toxin for WH[OVNLUPJP[` connected to pulmonary infections. weight compound of the cell wall. pathogenesis in humans as well. International Journal of Antimicrobial The :ULNL]LUZPZ vacuole forms Our aims are to use advanced 3D In animal models such as hamster Agents 48(4):401-408 close contacts with the endoplasmic tissue models in a bioreactor setup tracheal explants, TCT was shown Currently, preparative work is being reticulum and mitochondria and to study interaction of bacteria with carried out to investigate the host cell surface, bacterial transmigration, cell response to bacterial infection by and, after addition of neutrophils, RNA-seq analysis and, in particular, the fate of gonococci upon contact by single-cell RNA-seq, which is with cells of the immune system. challenging since B. pertussis is an We are developing imaging pro- extracellular pathogen and classical cedures, which will allow us to cell sorting of infected cells is not easily study infection processes in greater possible. Depending on the results depth. These include application of the RNA-seq analysis, further of expansion microscopy and lipid experiments will be performed with the staining using click chemistry. The 3D infection models, including the use connection between mitochondria, of B. pertussis strains with mutations sphingolipids, and :ULNL]LUZPZ, as in various virulence genes and the well as mitochondrial biogenesis in determination of the role of apparently the context of infection remain in our relevant signaling pathways of the focus. Further on, the cellular exit of host during B. pertussis infection. :ULNL]LUZPZ and the importance of cell death manipulation in this process represent one of the new directions in our research. TEM showing blebbing of denuded ciliated cells (green arrowhead) and nonciliated cell (yellow arrow- (K]HUJLK+[PZZ\LTVKLSZPU/ ,(HUKÅ\VYLZJLUJL)Z[HPUPUN5L\[YVWOPSZYLKPU[LYHJ[^P[O OLHKPUO;)4ZILMVYLSLM[HUKHM[LYPU[V_PJH[PVU^P[O;*;YPNO[:JHSLIHYZ!эT gonococci (green) at the tissue surface.

68 69 3.6 DEPARTMENT OF INTERNAL MEDICINE II

HERMANN EINSELE

ANDREAS BEILHACK

HARTWIG KLINKER

JÜRGEN LÖFFLER

The Department of Internal Medicine II at the University Hospital is part of the Medical Faculty of the University of Würzburg. Since 2004, it has been under the directorship of Prof. Dr. Hermann Einsele.

The department contains six research divisions, which include Hematology and Medical Oncology, Infectious Diseases, Gastroenterology, Hepatology, Clinical Immunology, and Psychosomatics. Excellent conditions for clinical research, teaching, and patient care exist due to close interdisciplinary interactions with the Center of Internal Medicine and Center of Operative Medicine.

It contains a new and state-of-the-art stem cell transplantation unit and the University Hospital Würzburg runs the second largest stem cell transplantation program in Germany, and implements many novel strategies. The division of 0UMLJ[PV\Z+PZLHZLZOHZILLUJLY[PÄLKHZVULVM[OLÄYZ[*LU[LYZVM0UMLJ[VSVN` in Germany. The clinical focuses of the division are HIV infections, chronic viral hepatitis, and opportunistic infections in immunocompromised patients.

Imageage: HilH ldee MMerkerte

70 71 3.6 DEPARTMENT OF INTERNAL MEDICINE II

INTERACTION OF ASPERGILLUS EXPERIMENTAL STEM CELL FUMIGATUS WITH HUMAN NATURAL TRANSPLANTATION

KILLER CELLS AND DENDRITIC CELLS PROF. ANDREAS BEILHACK Department of Internal Medicine II - ZEMM PROF. HERMANN EINSELE Chair of Internal Medicine II, Department of Internal Medicine II - ZIM [email protected] I +49 931 201 44040 www.beilhack.org [email protected] I +49 931 201 40001 www.ukw.de/medizinische-klinik-ii

RESEARCH INTERESTS [OL PKLU[PÄJH[PVU VM ZL]LYHS PTT\UV RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK SELECTED PUBLICATIONS dominant HCMV-peptides that have SELECTED PUBLICATIONS Einsele H, Ljungman P, Boeckh M I) (ZWLYNPSS\ZM\TPNH[\Z is a saprophytic been shown to induce T cell re- Ribechini E, Eckert I, Beilhack A, Employing and advancing state-of- In the past decade, we have been (2020) /V^ 0 [YLH[ *4= YLHJ[P]H[PVU fungus ubiquitously present in sponses in alloSCT patients, we Plessis N, Walzl G, Schleicher U, the-art methods and following an developing microscopy and imaging HM[LYHSSVNLULPJOLTH[VWVPL[PJZ[LTJLSS the environment that is one of the are still unable to reliably predict if a Ritter U, Lutz MB (2019) /LH[RPSSLK interdisciplinary research approach, techniques to investigate complex transplantation. most important fungal pathogens patient will develop HCMV reactivation Mycobacterium tuberculosis prime- the Beilhack lab aims to develop the immune processes in vivo. Besides Blood 135(19):1619-1629. IVVZ[ ]HJJPUH[PVU PUK\JLZ T`LSVPK causing severe invasive disease or will need a long-lasting antiviral KLYP]LK Z\WWYLZZVY JLSSZ ^P[O ZWSLLU next generation of immunotherapy and non-invasive imaging of luminescent Marty F, Ljungman P, Chemaly R, in immunocompromised patients. JOLTV[OLYHW` K\L [V HU PUZ\ѝJPLU[ KLUKYP[PJJLSSRPSSPUNJHWHIPSP[`. PTT\UVKPHNUVZ[PJZ MVY PUÅHTTH[VY` (M\TPNH[\Z infection PU]P]V we have Maertens J, Dadwal S, Duarte R, Inhaled conidia are internalized by HCMV-directed immune control. JCI Insight 5(13):128664 diseases, infections, and cancer. developed a high-resolution multicolor Haider S, Ullmann A, Katayama Y, airway epithelial cells or pulmonary SPNO[ZOLL[ Å\VYLZJLUJL TPJYVZJVW` Brown J, Mullane K, Boeckh M, Wertheimer T, Velardi E, Tsai J, Cooper K, Blumberg E, Einsele H, Snydman D, macrophages before undergoing Xiao S, Kloss CC, Ottmüller KJ, Mokhtari The fungus (ZWLYNPSS\ZM\TPNH[\Zcan (LSFM) technique to monitor complex Kanda Y, DiNubile M, Teal V, Wan H, germination and hyphal growth, leading HIGHLIGHTS & OUTLOOK Z, Brede C, deRoos P, Kinsella S, Palikuqi cause life-threatening fungal infections immune responses in intact organs Murata Y, Kartsonis N, Leavitt R (2017) to invasive aspergillosis. The lack of B, Ginsberg M, Young LF, Kreines F, after allogeneic hematopoietic cell of mice or in biopsies from patients. Lieberman SR, Lazrak A, Guo P, Malard *`[VTLNHSV]PY\Z 7YVWO`SH_PZ ^P[O YLSPHISL KPHNUVZ[PJ [VVSZ HUK LќLJ[P]L I) Within the CRC/Transregio 124, transplantation or in other situations Generating a plane of light to section Letermovir in Hematopoietic-Cell F, Smith OM, Shono Y, Jenq RR, Hanash ;YHUZWSHU[H[PVU treatments result in mortality rates of we aim to combine state-of-the-art AM, Nolan DJ, Butler JM, Beilhack A, when the immune system is through biological specimens, LSFM New England Journal of Medicine 40-90% in high-risk populations. research in mycology and immunology 4HUSL` 59 9HÄP : +\KHRV] 1( ]HU perturbed. Imbalances of local or can acquire multicolor images at 377(25):2433-2444 to gain novel insights into the den Brink MRM (2018) 7YVK\J[PVU VM systemic immune defense mecha- speeds 100 to 1,000 times faster )47I`LUKV[OLSPHSJLSSZPZJY\JPHSMVY II) Despite improved and novel antiviral pathophysiology of invasive mycoses LUKVNLUV\Z[O`TPJYLNLULYH[PVU nisms or disruption of cellular barriers than LN confocal microscopy. This Neuenhahn M, Albrecht J, Odendahl M, Science Immunology 3(19):eaal2736 Schlott F, Dössinger G, Schiemann M, drug therapies, HCMV infection to improve diagnosis and treatment. can result in invasive pulmonary method has the advantage of being Lakshmipathi S, Martin K, Bunjes D, in immunocompromised patients Together with members of the ZINF aspergillosis. Clearance of these able to visualize and quantify single Harsdorf S, Weissinger EM, Menzel H, remains associated with severe clinical and research groups from Jena, we Chopra M, Biehl M, Steinfatt T, Brandl A, infections depends on innate and cell interactions within their intact et al., Beilhack A (2016) ,_VNLUV\Z Verbeek M, Uharek L, Kröger N, Wagner complications and mortality due to will utilize high-throughput approaches HKHW[P]L PTT\UL LќLJ[VY JLSSZ )` three-dimensional tissue environment. E, Kobbe G, Schroeder T, Schmitt M, ;5-9 HJ[P]H[PVU WYV[LJ[Z MYVT HJ\[L Held G, Herr W, Germeroth L, Bonig H, /*4=ZWLJPÄJ PTT\UL YLZWVUZLZ to characterize infection-relevant net- .]/+ I` PUK\J[PVU VM OVZ[ ;YLN modulating the immune system, Recently, we employed LSFM to Tonn T, Einsele H, Busch DH, Grigoleit especially mediated by T and NK cells. works of (M\TPNH[\Z and host cells. expansion. we are analyzing the changes in uncover the time-resolved progression GU (2017) ;YHUZMLY VM TPUPTHSS` Thus, adoptive transfer of HCMV- To elucidate regulatory circuits in Journal of Experimental Medicine PU[LYHJ[PVUWH[[LYUZHUK[OLPYLќLJ[VU and spatial distribution of (M\TPNH[\Z THUPW\SH[LK*4=ZWLJPÄJ;JLSSZMYVT 213(9):1881–1900 Z[LTJLSSVY[OPYKWHY[`KVUVYZ[V[YLH[ directed donor-derived T and NK cells both the pathogen and the host, the the outcome of fungal infections. We during infection and the dynamics of *4=PUMLJ[PVUHM[LYHSSV/:*; as well as vaccination strategies of groups are systematically investigating aim to elucidate the interplay of host PTT\UL JLSS YLJY\P[TLU[ PU KPќLYLU[ Leukemia 31(10):2161-2171 donor and/or recipient are increasingly the pathogen itself and its interaction AWARDS and pathogen under in vivo conditions scenarios of immunosuppression. attractive therapeutic approaches with single cell types (LN epithelial or Award of the foundation Forschung Hilft! to develop novel strategies to improve to improve HCMV-directed immune DC), complex infection and mouse (2019) disease outcome. As members of the Collaborative reconstitution post-transplant. Despite models, and clinical samples using Research Center TRR124 FungiNet, functional genomics. In the next years we are investigating dynamic immune- we aim to provide new insights into pathogen interactions in mouse the pathogenicity of (M\TPNH[\Z and models in vivo. As members of the identify diagnostic biomarkers and DFG GRK 2157 3D Infect, we combine potential targets for new antimycotic microscopy techniques and organ- approaches. on-a-chip models. Currently, we are L_WSVYPUNOV^J`[VRPULUL[^VYRZÄUL II) We aim to better identify patients at tune host defense mechanisms within risk for HCMV disease and to improve the local tissue environment and the selection of HCMV-directed regulate tissue-resident immune cell T and NK cells for adoptive transfer subsets. Currently we are expanding and of HCMV-derived peptides for our endeavor to an invertebrate vaccination strategies. Here, we will model (Bombyx mori) to investigate study the reconstitution of antiviral host-pathogen interactions and novel T and NK cell responses in alloSCT antifungal strategies. Combining basic patients, the respective stem cell donor, research with our close ties to the and healthy donors using novel sets of clinics we aim at improving diagnostics HCMV epitopes. We aim to optimize and therapeutic options for patients immune monitoring, prediction of Z\ќLYPUN MYVT JOYVUPJ VWWVY[\UPZ[PJ (ZWLYNPSS\ZM\TPNH[\Z hyphae and activated human natural killer (NK) cells. HCMV-related complications, and 3PNO[ZOLL[Å\VYLZJLUJLTPJYVZJVW`[VYL]LHSOVZ[WH[OVNLUPU[LYHJ[PVUZTV\ZLS\UNSLM["KL[HPSYPNO[ infections. improve adoptive T cell therapies.

72 73 3.6 DEPARTMENT OF INTERNAL MEDICINE II

DIVISION OF INFECTIOUS DISEASES IMMUNITY AGAINST ASPERGILLUS SPP.

PROF. HARTWIG KLINKER PROF. JÜRGEN LÖFFLER Department of Internal Medicine II - ZIM Department of Internal Medicine II [email protected] I +49 931 201 40043 ORHυHUBM#XNZGH, www.ukw.de/medizinische-klinik-ii/infektiologie www.ukw.de/medizinische-klinik-ii

RESEARCH INTERESTS virostatic and antifungal agents. One RESEARCH INTERESTS the fungus. Furthermore, we have SELECTED PUBLICATIONS major focus is the pharmacokinetic SELECTED PUBLICATIONS shown that NK cells interact with and Yuen MF, Schiefke I, Yoon JH, Ahn SH, The group uses laboratory and clinical- evaluation of HIV protease inhibitors Zoran T, Weber M, Springer J, White L, (ZWLYNPSS\Z M\TPNH[\Z (AF) is a major recognize AF via the NK cell receptor Heo J, Kim JH, Chan HLY, Yoon KT, based approaches to investigate inno- (PI) and non-nucleoside reverse )H\LY 1 :JOVILY ( 3€ўLY * cause of morbidity and mortality CD56, which results in the release of Klinker H, et al. (2019) 95(0U[LYMLYLUJL vative anti-infective strategies in the transcriptase inhibitors (NNRTI) during Seelbinder B, Hünniger K, Kurzai O, in immunocompromised patients. Th1-like cytokines and fungal killing. ;OLYHW` ^P[O (9* 9LZ\S[Z PU ÄLSKZVM/0=PUMLJ[PVUJOYVUPJOLWH[P[PZ antiretroviral therapy in patients Scherag A, Schäuble S, Morton O, Cells of the innate immune system Using live cell imaging and dStorm 7YVSVUNLK/)Z(N9LZWVUZLPU7H[PLU[Z Einsele H, Linde J, /ŌυHU - (2019) ^P[O*OYVUPJ/LWH[P[PZ)0UMLJ[PVU B and C, as well as opportunistic with HIV infection. New methods ;YLH[TLU[ ^P[O L[HULYJLW[ HUK SV^ YLJVNUPaL[OLM\UN\ZHUKP[ZKPќLYLU[ microscopy, we have revealed that Hepatology doi: 10.1002/hep.31008 infections in immunocompromised are currently being developed for monocyte concentration contribute morphologies by distinct pattern DCs are key players in the activation hosts. The pharmacokinetic analysis the determination of bictegravir and [V [OL YPZR VM PU]HZP]L HZWLYNPSSVZPZ recognition receptors (PRRs), which of NK cells and that this activation PU WH[PLU[Z WVZ[ HSSVNLULPJ Z[LT JLSS Knop V, Hofmann WP, Buggisch P, center focuses on the detection and doravirin concentrations. Many clinical PUK\JLJLSSZWLJPÄJHZ^LSSHZNLULYHS is mediated by the C-type lectin Klinker H, Mauss S, Günther R, transplantation. /PUYPJOZLU / / WWL + 7MLPќLY X\HU[PÄJH[PVUVMKPќLYLU[HU[P]PYHSHUK Z[\KPLZ^LYLWLYMVYTLKPU[OLÄLSKVM 6FLHQWLðF5HSRUWV 9(1):17231 defense mechanisms. The most dectin-1. Recently, our group has Vornkahl H, Simon KG, Berg T, Manns antifungal agents. chronic hepatitis B and C. important cells of the innate immune performed extensive studies on the MP, Friedrich-Rust M (2019) Estimation /ŌυHU -, Ebel F (2018) Size matters system are alveolar macrophages, role of chimeric antigen receptors VMSP]LYÄIYVZPZI`UVUJVTTLYJPHSZLY\T The section of Infectious Diseases is a The antifungal triazoles voriconazole - how the immune system deals with granulocytes, natural killer (NK) cells, (CAR) for antigens of AF on NK markers in comparison with transient fungal hyphae. LSHZ[VNYHWO` PU WH[PLU[Z ^P[O JOYVUPJ clinical center within the German Liver and posaconazole are broadly used Microbes & Infection 20(9-10):521-25 as well as dendritic cells (DC). Our cells and T cells. We will continue to OLWH[P[PZ * ]PY\Z PUMLJ[PVU YLJLP]PUN Foundation. Since 2005, the study- for either treatment or prophylaxis of group aims to better understand the functionally characterize PBMC and KPYLJ[HJ[PUNHU[P]PYHS[YLH[TLU[ center has participated in the world- invasive fungal infections. Voriconazole Ziegler S, Weiss E, Schmitt A, Schlegel J, interaction of AF with the innate and NK cells isolated from patients after Journal of Viral Hepatitis 26(2):224-30 wide study-network for strategical is metabolized by the CYP P450- Burgert A, Terpitz U, Sauer M, Moretta adaptive immune system, and with allogeneic SCT during their ex vivo L, Sivori S, Leonhardt I, Kurzai O, Schultheiß M, Kling S, Lenker U, von HIV-studies INSIGHT (International Net- system, while posaconazole inhibits Einsele H, /ŌυHU - (2017) *+ 0Z H other pathogens and to characterize interaction with fungal pathogens. Bibra M, Rosenkranz B, Klinker H work for Strategic Initiatives in Global the cytochrome P450 enzymes. For 7H[OVNLU 9LJVNUP[PVU 9LJLW[VY VU genetic susceptibility to the fungus. Another major research interest is (2018) Lopinavir serum concentrations HIV Trials) sponsored by the National pharmacokinetic studies, we have /\THU5H[\YHS2PSSLY*LSSZ the genetic susceptibility of patients VMJYP[PJHSS`PSSPUMHU[Z!HWOHYTHJVRPUL[PJ Institutes of Health in the USA (see developed a combined HPLC- 6FLHQWLðF5HSRUWV 7(1):6138 to AF infections. Genotyping of a PU]LZ[PNH[PVUPU:V\[O(MYPJH http://www.insighttrials.org). assay for the determination of serum HIGHLIGHTS & OUTLOOK SHYNL +5( IHUR PKLU[PÄLK :57Z [OH[ Medical Microbiology & Immunology Hellmann A, Lother J, Wurster S, Lutz M, 207(5-6):339-343 concentrations of both triazoles. Schmitt A, Morton O, Eyrich M, are potentially associated with the Czakai K, Einsele H, /ŌυHU - (2017) The research of my group focuses on occurrence of (ZWLYNPSS\Z infections. HIGHLIGHTS & OUTLOOK Letermovir is a new antiviral drug /\THU HUK T\YPUL PUUH[L PTT\UL PTT\UL YLJVNUP[PVU VM (- WH[PLU[Z» In parallel, we study the interaction AWARDS approved for prophylaxis of CMV JLSS WVW\SH[PVUZ KPZWSH` JVTTVU HUK genetic susceptibility to this fungus, of AF with other pathogens of the KPZ[PUJ[ YLZWVUZL WH[[LYUZ K\YPUN [OLPY “Top Mediziner” in Germany for The laboratory specializes in devel- disease in CMV-positive adults PU]P[YVPU[LYHJ[PVU^P[O[OLWH[OVNLUPJ and the molecular diagnosis of lung, focusing on CMV. Using dual infectious diseases in the ranking of the oping and implementing methods receiving an allogeneic hematopoietic TV\SK(ZWLYNPSS\ZM\TPNH[\Z invasive fungal infections. We have RNA-seq, and optionally in addition “Focus” magazine (2019 & 2020) for evaluating stem cell transplant. Being a substrate Frontiers in Immunology 8:1716 revealed TLR2-, TLR4-, and dectin- a viral pathogen, with subsequent and therapeutic drug monitoring of of the hepatic uptake transporter 1-dependent activation of DCs by siRNA knockdown of selected target OATP1B1/3, coadministration of NLULZ ^L HPT [V KLÄUL ZWLJPÄJ OATP inhibitors and genetic variabi- immune-relevant pathways involved lities lead to clinically relevant changes in aspergillosis. Our future studies will PUKY\NL_WVZ\YL(Z[OLÄYZ[NYV\W^L investigate the role of CD56 as immune could establish a high performance receptor on NK cells using CRISPR- liquid chromatography (HPLC) assay Cas technology. We will also strive to for determination of letermovir concen- better understand the pathophysiology tration and evaluated letermovir serum of Mucorales infections. Recently, we JVUJLU[YH[PVUZ PU KPќLYLU[ JSPUPJHS have led several clinical studies on settings (Dr. Nora Isberner). the diagnosis of fungal infections, and we are active leading contributors to The determination of plasma concen- the standardization of(ZWLYNPSS\Z and trations of antiviral and antifungal Mucorales diagnosis worldwide (I am drugs will provide insights into the the head of the Fungal PCR Initiative individual pharmacokinetics of antiviral Steering Committee). Overall, our [YLH[TLU[ZPUKPќLYLU[WH[PLU[NYV\WZ HPTPZ[VKL]LSVWWH[PLU[ZWLJPÄJYPZR and will contribute to improving the WYVÄSLZ HUK PUKP]PK\HS THUHNLTLU[ LѝJHJ` HUK ZHML[` VM SVUN[LYT Z[YH[LNPLZ MVY WH[PLU[Z Z\ќLYPUN MYVT treatment. AF infection. HPLC run of the determination of letermovir (MK8228, concentration 4.731 ng/ml). Summary of the current research projects with a focus on NK cell – (ZWLYNPSS\Z interaction analyses. SFB = sorafenib = internal standard.

74 75 3.7 INSTITUTE OF SYSTEMS IMMUNOLOGY

GEORG GASTEIGER

MERCEDES GOMEZ DE AGÜERO

MARTIN VAETH

;OL 0UZ[P[\[L VM :`Z[LTZ 0TT\UVSVN` ^HZ MV\UKLK PU H JVSSHIVYH[P]L LќVY[ between the Max Planck Society and the University of Würzburg and is located on the Medical Campus. With the cooperation agreement signed in 2013, the Institute began its research in 2017 with the appointments of Prof. Dr. Wolfgang Kastenmüller and Prof. Dr. Georg Gasteiger as Chairs of the newly founded Departments of Systems Immunology and Systems Immunology II, respectively, at the University of Würzburg.

Research at the Institute pursues a holistic approach to study the immune system and its interactions with the organism as a whole. One focal area is the protection that the immune system can provide against pathogens or cancer cells. Diseases triggered by the immune system such as multiple sclerosis or rheumatism are another research focus.

In particular, the Institute focuses on where and how cells of the immune system PU[LYHJ[ [V HJOPL]L HU LќLJ[P]L PTT\UL YLZWVUZL VY [V WYL]LU[ PUÅHTTH[VY` disease processes. Researchers at the Institute of Systems Immunology are developing new genetic tools that allow for the visualization of a wide variety of ZWLJPÄJJLSS[`WLZ[V[LZ[[OLPYM\UJ[PVU;OL\S[PTH[LNVHSPZ[V\UKLYZ[HUK[OL basic principles for a successful immune response against infectious agents and tumors and to use them therapeutically.

ImageImImagmagemagmama ::H HHilHi dedeeM MeM errkerkrkertkertkeere t

76 77 3.7 INSTITUTE OF SYSTEMS IMMUNOLOGY

TISSUE IMMUNITY HOST-MICROBIAL INTERACTIONS

PROF. GEORG GASTEIGER DR. MERCEDES GOMEZ DE AGÜERO Chair of Systems Immunology II, Institute of Systems Immunology Institute of Systems Immunology [email protected] I +49 931 31 89599 [email protected] I +49 931 31 80303 www.med.uni-wuerzburg.de/systemimmunologie www.med.uni-wuerzburg.de/systemimmunologie

RESEARCH INTERESTS examined lymphoid and non-lymphoid RESEARCH INTERESTS barrier function. With a quasi-exclu- SELECTED PUBLICATIONS VYNHUZ>LOH]LUV^PKLU[PÄLK[PZZ\L SELECTED PUBLICATIONS sive uterine development, it is largely Zeis P, Lian M, Fan X, Herman JS, In addition to mobile cells of the associated ILC progenitors that enable Mooser C, Gomez de Agüero M, Ganal- Mammalians harbor trillions of millions accepted that the ontogeny and Hernandez DC, Gentek R, Elias S, et al., immune system that migrate through [OLSVJHSKPќLYLU[PH[PVU[PZZ\LZWLJPÄJ Vonarburg SC (2018) :[HUKHYKPaH[PVU of microorganisms, including bacteria, KPќLYLU[PH[PVUVM[OLZRPU^V\SKVJJ\Y Gasteiger G (2020) In situ maturation our body, most anatomical compart- imprinting, and specialization of ILCs. PU OVZ[TPJYVIPV[H PU[LYHJ[PVU Z[\KPLZ! fungi, protozoa, , and viruses, independently of the microbiota and HUK[PZZ\LHKHW[H[PVUVM[`WLPUUH[L ments are populated by resident In collaboration with ZINF research JOHSSLUNLZNUV[VIPVSVN`HZH[VVSHUK which collectively form the commensal is genetically programmed. We aim S`TWOVPKJLSSWYVNLUP[VYZ. perspective. Immunity (accepted) immune cells that act as local sentinels groups, we are currently investigating Current Opinion Microbiology 44:50-60 microbiota providing the host with to revise the genetic preprograming and contribute to homeostasis, repair, how these mechanisms determine essential vitamins, energy, and dogma of the development of the Straub T, Freudenberg MA, Schleicher U, and function of their host tissue. local host-pathogen interactions in Macpherson AJ, Gomez de Agüero M, pathogen exclusion. It is now largely skin and investigate the relative Bogdan C, Gasteiger G, Pircher H Understanding the development, reg- [PZZ\LZWLJPÄJTPJYVLU]PYVUTLU[Z Ganal-Vonarburg SC (2017) How accepted that mammalian immunity contribution of microbiota to the (2018) )HJ[LYPHS JVPUMLJ[PVU YLZ[YHPUZ U\[YP[PVU HUK [OL TH[LYUHS TPJYVIPV[H HU[P]PYHS *+  ;JLSSYLZWVUZL ]PH 37: ulation, and function of these cells is shape the neonatal immune system. is profoundly stimulated by exposure proper development of the neonatal PUK\JLKPUOPIP[VY`52JLSSZ therefore relevant for a broad range We are also investigating local mech- Nature Reviews Immunology 17(8): to microbiota and/or their molecular skin barrier. Nature Communications 9(1):4117 of physiological and pathological HUPZTZMVY[OL¸ZLSLJ[PVU¹VYÄUL[\UPUN 508-517 metabolites. Recently, several studies conditions. We are investigating how VMH[PZZ\LHUKZP[LZWLJPÄJYLWLY[VPYL OH]L KLÄULK H JYP[PJHS ^PUKV^ LHYS` Muschaweckh A, Buchholz VR, innate and adaptive lymphocytes of resident memory cells that can Hacini-Rachinel F, Gomez de Agüero M, in life for the microbiota to shape Fellenzer A, et al., Gasteiger G (2016) Kanjarawi R, Moro-Sibilot L, Le Luduec HIGHLIGHTS & OUTLOOK (U[PNLUKLWLUKLU[JVTWL[P[PVUZOHWLZ HKQ\Z[[VZWLJPÄJ[PZZ\LLU]PYVUTLU[Z optimally recognize antigens present JB, Macari C, Boschetti G, Bardel E, the immune system. Our previous [OL SVJHS YLWLY[VPYL VM [PZZ\LYLZPKLU[ and how they function as part of local in discernible regions or niches within Langella P, Dubois B, Kaiserlian D work revealed the pivotal role played We use a sophisticated gnotobiotic TLTVY`*+ ;JLSSZ immune cell networks. Our aim is to a given tissue. Such mechanisms (2017) 0U[LZ[PUHSKLUKYP[PJJLSSSPJLUZPUN by microbiota during pregnancy on research model based on an Journal of Experimental Medicine [OYV\NO ;VSSSPRLYLJLW[VY  PZ YLX\PYLK 213(13):3075-3086 understand the context-dependent may be critical to generate local pools MVY VYHS [VSLYHUJL PU HSSLYNPJ JVU[HJ[ the development of the immune auxotrophic Escherichia coli strain physiological and pathological func- of resident memory T cells that can KLYTH[P[PZ system. Indeed, maternal microbiota for exclusive gestational colonization Bedoui S, Gebhardt T, Gasteiger G, tions of resident lymphocytes for JVU[YVSWH[OVNLUZWLYZPZ[PUNPUKLÄULK Journal of Allergy and Clinical metabolites cross the placenta and ^P[OZ[LYPSLVќZWYPUN-SV^J`[VTL[Y` Kastenmüller W (2016) 7HYHSSLSZ HUK immune homeostasis as well as anatomical regions, and to strategically Immunology 141(1):163-170 ZOHWL[OLVќZWYPUNPU[LZ[PUHSPTT\UP[` histology, scRNA sequencing, and KPќLYLUJLZ IL[^LLU PUUH[L HUK HKHW PUMLJ[PV\ZHUKPUÅHTTH[VY`KPZLHZLZ WVZP[PVU ; JLSSZ ^P[O ZWLJPÄJP[` MVY to prepare the newborn for the metabolic analysis of the pre- and tive lymphocytes. Gomez de Agüero M*, Ganal- Nature Immunology 17(5):490-4 regionally distinct heterogeneous Vonarburg S*, Uchimira Y, Fuhrer T, challenges that occur from birth. postnatal skin allowed us to show microbial communities. Rupp S, Steinert A, Hapfelmeier S, that maternal microbiota shapes the Gasteiger G, Fan D, Dikyi S, Lee SY, HIGHLIGHTS & OUTLOOK Sauer U, McCoy KD*, Macperson AJ* In the passage from the protected development of the skin. Maternal Rudensky AY (2015) ;PZZ\L YLZPKLUJ` In our quest to understand the (2016) 5LVUH[HS PUUH[L PTT\UL maternal uterus to the external microbiota regulates gene expression KL]LSVWTLU[ KYP]LU I` [OL TH[LYUHS VMPUUH[LS`TWOVPKJLSSZPUS`TWOVPKHUK Our previous work revealed that development and maintenance of environment full of challenges, the of epidermal stem cells. The UVUS`TWOVPKVYNHUZ microbiota. Science 350(6263):981-5 currently known subsets of innate the “functional architecture” of local Science 351(6279):1296 skin barrier plays a key role. The KPќLYLU[PH[PVU VM [OL RLYH[PUVJ`[LZ [V lymphoid cells (ILCs) are locally networks of tissue lymphocytes, we outer layer of the skin, the epidermis, a more mature or specialized stage is maintained as tissue-resident cells in all are employing genetic mouse models, concentrates most of the cutaneous impaired in the absence of maternal L_WLYPTLU[HS TVKLSZ VM PUÅHTTH[VY` microbial cells. In addition, maternal diseases, tumors, and infection, as well microbiota modulates the recruitment as single-cell genomics and advanced and maturation of epidermal immune PTHNPUN0UKPќLYLU[WYVQLJ[Z^LZ[\K` cells, such as Langerhans cells. Finally, the skin, lung, female reproductive the permeability barrier and wound tract, liver and salivary gland, which all   healing in neonates is enhanced by represent clinically relevant infection     gestational colonization. niches.          We currently focus our research on in-       depth investigation of the mechanisms     underlying the development of the skin, the early and late consequences VM ILPUN IVYU ^P[O H KLÄJPLU[ ZRPU barrier, and the strategies for acute    restoration. Our studies will contribute    to a better understanding of the development of the skin, the largest organ of the body.

Local frontline defense: T cells (blue) and ILC2 (red) lining the intestinal epithelium (A). Tissue-resident Maternal microbial derived metabolites shape embryonic skin development positively impacting on the memory T cells in the skin (B). barrier function of the neonates.

78 79 3.7 INSTITUTE OF SYSTEMS IMMUNOLOGY

METABOLISM AND IMMUNE CELL SIGNALLING

DR. MARTIN VAETH Institute of Systems Immunology [email protected] I +49 931 31 82491 www.med.uni-wuerzburg.de/systemimmunologie

RESEARCH INTERESTS to treat immune-related pathologies, SELECTED PUBLICATIONS such as persistent infections. Kahlfuss S, Kaufmann U, Concepcion A major challenge for the immune AR, Noyer L, Raphael D, Vaeth M, system is the discrimination between Yang J. Pancholi P, Maus M, Muller ºZLSM» [PZZ\L HUK ºUVUZLSM» HU[PNLUZ HIGHLIGHTS & OUTLOOK J, Kozhaya L, Khodadadi-Jqmayran, that are associated with infectious Sun Z, Shaw P, Unutmaz D, Stathopulos PB, Feist C, Cameron SB, Turvey pathogens or malignant cells to Lymphocytes are critical mediators SE, Feske S (2020) :;04TLKPH[LK WYL]LU[[OLKLZ[Y\J[PVUVM[OLIVK`»Z of adaptive immune responses JHSJP\T PUÅ\_ JVU[YVSZ HU[PM\UNHS own healthy tissues. Immunological to pathogens and provide long- PTT\UP[`HUK[OLTL[HIVSPJM\UJ[PVUVM UVUWH[OVNLUPJ;OJLSSZ [VSLYHUJL PZ [OL ÄUL I\[ ÅL_PISL term protection by the formation of EMBO Molecular Medicine 12(8): balance between immunity to infection immunological memory. The research e11592 and the prevention of autoimmunity, in our laboratory investigates the dysregulation of which can result in metabolic control of lymphocyte Vaeth M, Kahlfuss S, Feske S (2020) severe immunological pathologies. KPќLYLU[PH[PVU M\UJ[PVU HUK TLTVY` *9(**OHUULSZHUK*HSJP\T:PNUHSPUN PU;*LSS4LKPH[LK0TT\UP[` MVYTH[PVU PU KPќLYLU[ [PZZ\L LU]PYVU Trends in Immunology S1471-4906 Our laboratory investigates the ments. We showed recently that cell (20)30149-6 underlying molecular principles of cycle entry, clonal expansion, and immunological tolerance focusing [OL LќLJ[VY KPќLYLU[PH[PVU VM ]PY\Z Vaeth M, Wang YH, Eckstein M, Yang J, Silverman GJ, Lacruz RS, Kannan K, on the metabolic programming of ZWLJPÄJ ; JLSSZ KLWLUKZ JYP[PJHSS` VU 2+ 2+ Feske S (2019) ;PZZ\L YLZPKLU[ HUK immune cells in the context of viral calcium (Ca ). Ca signals induce a MVSSPJ\SHY ;YLN JLSS KPќLYLU[PH[PVU PZ infection and immune tolerance. metabolic switch in naïve T cells and YLN\SH[LKI`*9(*JOHUULSZ Over the last decades, it became change their metabolic phenotype Nature Communications 10(1):1183 JSLHY[OH[ºPTT\UVTL[HIVSPZT»PZUV[ from a quiescent to a high-rate Vaeth M, Feske S (2018) 5-(;JVU[YVS solely important to provide energy anabolic state that is characterized VM PTT\UL M\UJ[PVU! 5L^ -YVU[PLYZ MVY required for the proliferation and by elevated aerobic glycolysis and HU(IPKPUN;YVVWLY LќLJ[VY M\UJ[PVU VM S`TWOVJ`[LZ I\[ mitochondrial metabolism. This meta- F1000 Research 7:260 also controls gene expression and bolic re-programming of naïve T cells LWPNLUL[PJ WYVNYHTTPUN VM KPќLYLU[ is critical for the clonal expansion of immune cells. A deeper understanding HU[PNLUZWLJPÄJ S`TWOVJ`[LZ HUK of these metabolic regulatory circuits controls the formation of memory promises new therapeutic avenues T cells. Glucose metabolism plays a central role in both the activation and KPќLYLU[PH[PVUVM;JLSSZI\[LSL]H[LK glycolysis can also promote functional exhaustion of lymphocytes and curtail LѝJPLU[HU[P]PYHSPTT\UP[`)HZLKVU our original observation that glucose metabolism is a central regulator of both T cell-mediated immunity and tolerance, we aim to further dissect the underlying molecular, transcriptional and epigenetic consequences of elevated glucose metabolism and investigate if metabolic programming of lymphocytes is a feasible strategy to optimize T cell-mediated immunity to pathogens and malignant diseases.

T follicular helper (TFH) cells migrate into B cell follicles and undergo metabolic changes after interaction with germinal center (GC) B cells.

80 81 3.8 HELMHOLTZ INSTITUTE FOR RNA-BASED INFECTION RESEARCH

LARS BARQUIST

CHASE BEISEL

NEVA CALISKAN

MATHIAS MUNSCHAUER

ANTOINE-EMMANUEL SALIBA

REDMOND SMYTH

The Helmholtz Institute for RNA-based Infection Research (HIRI) was established PU4H`PUHQVPU[LќVY[I`[OL/LSTOVS[a*LU[YLMVY0UMLJ[PVU9LZLHYJO/A0 in Braunschweig and the University of Würzburg. Located on the Würzburg 4LKPJHS*HTW\Z[OL/090PZ[OLÄYZ[YLZLHYJOPUZ[P[\[PVU^VYSK^PKL[VM\SS`MVJ\Z on the role of RNA in infection processes. As a federal Institute, the HIRI pioneers an integrative approach to exploit the vast potential of RNA as a diagnostic, a drug, and a therapeutic target for new strategies to combat infectious diseases.

Lead by Acting Director Jörg Vogel, the HIRI focuses on four central research areas: basic research on bacterial pathogens, on viruses, and on the host immune response provides a comprehensive understanding of the role of RNA in infections. These three general areas are complemented by applied research on RNA delivery for diagnostic and therapeutic purposes.

The synergy between HIRI research groups and the infection research and translational competences at the University of Würzburg as well as at the HZI )YH\UZJO^LPN JYLH[LZ \UPX\L VWWVY[\UP[PLZ [V LќLJ[P]LS` JVU]LY[ RUV^SLKNL based on fundamental research into applications to establish novel therapeutic and diagnostic strategies for the treatment of infectious diseases.

Image: doranth post architekten GmbH

82 83 3.8 HELMHOLTZ INSTITUTE FOR RNA-BASED INFECTION RESEARCH

INTEGRATIVE INFORMATICS FOR RNA INFECTION BIOLOGY

JUN. PROF. LARS BARQUIST PROF. CHASE BEISEL Helmholtz Institute for RNA-based Infection Research Helmholtz Institute for RNA-based Infection Research [email protected] I +49 931 31 82513 [email protected] I +49 931 31 85346 www.helmholtz-hiri.de www.helmholtz-hiri.de

RESEARCH INTERESTS increasingly not in data generation, but RESEARCH INTERESTS ÅHURPUN H [HYNL[ ZLX\LUJL ;V^HYKZ SELECTED PUBLICATIONS in data analysis. We use the bacterial SELECTED PUBLICATIONS exploiting CRISPR-Cas systems, Mika-Gospodorz B, Giengkam S, The group, established in 2018, uses pathogen Salmonella enterica as a Liao C, Ttofali F, Slotkowski RA, Denny CRISPR-Cas systems comprise RNA- ^L ÄYZ[ KLTVUZ[YH[LK [OH[ [OLZL Westermann AJ, Wongsantichon J, Kion- data science technologies, including model system for the development SR, Cecil TD, Leenay RT, Keung AJ, guided immune systems that have systems could be harnessed as anti- Crosby W, Chuenklin S, Wang LC, et visualization, machine learning, and of systems approaches leveraging Beisel CL (2019) 4VK\SHY VULWV[ formed the basis for revolutionary microbial agents and have been # # al., Vogel J, Barquist L , Salje J (2020) statistical modelling, to extract bio- these technologies to gain insight into HZZLTIS` VM *90:79 HYYH`Z LUHISLZ genome-editing technologies. The actively developing delivery vehicles +\HS95(ZLXVM6YPLU[PH[Z\[Z\NHT\ZOP SPIYHY` NLULYH[PVU HUK YL]LHSZ MHJ[VYZ PUMVYTZ VU OVZ[WH[OVNLU PU[LYHJ[PVUZ logical insight from high-throughput virulence processes. PUÅ\LUJPUNJY95(IPVNLULZPZ group aims to understand the func- based on engineered bacteriophages. MVY [OPZ ULNSLJ[LK PU[YHJLSS\SHY O\THU genomic and post-genomic data. We Nature Communications 10(1):2948 tional diversity of these immune Finally, we have established several WH[OVNLU use these technologies to understand systems in prokaryotes and how they collaborations to elucidate the func- Nature Communications doi: 10.1038/ [OLLќLJ[ZVM95(IHZLKYLN\SH[PVUPU HIGHLIGHTS & OUTLOOK Marshall R, Maxwell CS, Collins SP, can be further exploited to advance tional domains within guide RNAs s41467-020-17094-8 Jacobsen T, Luo ML, Begemann MB, IHJ[LYPHHUKUVUJVKPUN95(»ZYVSLPU Gray BN, January E, Singer A, He Y, the study, diagnosis, and treatment of and to develop DNA-based delivery Ryan D, Jenniches L, Reichardt S, host-pathogen interactions as well as Our work focuses on developing data Beisel CL*, Noireaux V* (2018) 9HWPK infectious diseases in humans. Within vehicles for CRISPR ribonucleoprotein Barquist L, Westermann AJ (2020) A pathogen evolution. analysis and interpretation approaches HUK :JHSHISL *OHYHJ[LYPaH[PVU VM this broad focus, the group seeks to complexes into mammalian cells. In OPNOYLZVS\[PVU [YHUZJYPW[VTL THW for functional genomics data at the *90:79 ;LJOUVSVNPLZ

84 85 3.8 HELMHOLTZ INSTITUTE FOR RNA-BASED INFECTION RESEARCH

RECODING MECHANISMS IN DECODING RNA-PROTEIN INFECTIONS INTERACTOMES OF REGULATORY RNA

JUN. PROF. NEVA CALISKAN IN INFECTION Helmholtz Institute for RNA-based Infection Research DR. MATHIAS MUNSCHAUER [email protected] I +49 931 31 85298 Helmholtz Institute for RNA-based Infection Research www.helmholtz-hiri.de [email protected] I +49 931 31 86951 www.helmholtz-hiri.de

RESEARCH INTERESTS MYHNTLU[Z H[ KPќLYLU[ Z[HNLZ VM RESEARCH INTERESTS interactions that enable lncRNA SELECTED PUBLICATIONS infection to monitor in vivo translation SELECTED PUBLICATIONS functions. Bock LV*, Caliskan N*, Korniy N, 95(]PY\ZLZSPRLPUÅ\LUaHHUKJVYVUH WYVÄSLZ"LJ\YYLU[S`JOHYHJ[LYPaL elements that mediate these inter- pathogens, particularly RNA viruses. Foundation, Germany (2018) ventional translation events in host these factors by loss/gain of function Helmholtz Young Investigator Award actions. We seek to elucidate the We aim at understanding their (2018) cellular genes upon HIV-1 infection, and infection assays. composition of lncRNA complexes direct interactions with the host cell sequencing of ribosome protected and aim to identify biochemical proteome in order to identify host • Using cutting-edge confocal as- dependency factors and characterize sisted optical tweezers, we discov- underlying modes of regulation. ered that the binding of the trans- In this context, we have recently acting viral protein 2A leads to the started to systematically identify stabilization of the wild type cardiovirus the compendium of proteins bound frameshift RNA structure. to the genomic RNAs of several positive-sense RNA viruses. To this • We have established infection end, our group is developing and assays and cell culture conditions applying cutting-edge technologies to globally study host cell translation to characterize direct interactions of in T-cells, as well as successfully individual RNA species with proteins prepared RNA and Ribo-seq libraries at high resolution and in a quantitative from HIV-1 infected cells. manner. Ultimately, we hope to utilize insights into the mechanisms • >L PKLU[PÄLK ZTHSS TVSLJ\SL of RNA function in order to improve interaction partners of frameshift our understanding and ability to treat RNAs, which can modulate the infectious disease. LѝJPLUJ` VM YLJVKPUN VU [OL :(9: CoV-2 mRNA. This can be a promising Overview of Caliskan lab projects: 1) translational dynamics, 2) regulation of recoding, and 3) high- therapeutic strategy to interfere with ;OLTHTTHSPHUUVUώJVKPUN95(YLZWVUZL[VIHJ[LYPHSVY]PYHSPUMLJ[PVUZ throughput approaches to identify novel recoding events. viral replication. Adapted from Munschauer and Vogel, 2018, EMBO Journal.

86 87 3.8 HELMHOLTZ INSTITUTE FOR RNA-BASED INFECTION RESEARCH

SINGLE-CELL ANALYSIS GENOME ARCHITECTURE AND EVOLUTION OF RNA VIRUSES

DR. ANTOINE-EMMANUEL SALIBA JUN. PROF. REDMOND SMYTH Helmholtz Institute for RNA-based Infection Research Helmholtz Institute for RNA-based Infection Research [email protected] I +49 931 31 81341 [email protected] I +49 931 31 89152 www.helmholtz-hiri.de www.helmholtz-hiri.de

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK RESEARCH INTERESTS binds a trans-cellular or viral factor SELECTED PUBLICATIONS SELECTED PUBLICATIONS that could eventually be targeted in Imdahl F*, Vafadarnejad E*, Homberger The ability of pathogens to subvert In the context of infection, we Smyth RP, Smith MR, Jousset A-C, We study RNA viruses, such as antiretroviral therapy. Beyond HIV-1, C, Saliba AE#, Vogel J# (2020) host cells for survival or replication have pioneered the use of scRNA- Despons L, Laumond G, Decoville T, /0= PUÅ\LUaH HUK :(9:*V= we are interested in discovering the :PUNSLJLSS 95(ZLX\LUJPUN YLWVY[Z is in part due to their astonishing seq to investigate heterogeneity in Cattenoz P, Moog C, Jossinet F, Mougel using an RNA-centric approach that general principles underlying the NYV^[OJVUKP[PVUZWLJPÄJ NSVIHS [YHUZ JHWHJP[` [V HKVW[ KPќLYLU[ SPMLZ[`SLZ the response of macrophages to M, Paillart J-C, von Kleist M & Marquet focuses on the folding of the RNA regulation of translation by RNA JYPW[VTLZVMPUKP]PK\HSIHJ[LYPH R (2018) 0UJLSST\[H[PVUHSPU[LYMLYLUJL Nature Microbiology in press Characterizing and understanding Salmonella, focusing on bacteria with THWWPUN L_WLYPTLU[ PU JLSS 404, genome into complex 3D structures. structure. To this end, we have re- infected cells at single-cell level KPќLYLU[NYV^[OZ[H[\ZPUJS\KPUNUVU PKLU[PÄLZ [OL » WVS`HKLU`SH[PVU ZPNUHS These RNA structures play key roles cently repurposed a next generation Schulte-Schrepping J*, Reusch N*, resolution using genome-wide trans- YLWSPJH[PUNºWLYZPZ[LYZ»[OH[OH]LILLU HZ H K\HS YLN\SH[VY VM /0= NLUVTPJ in viral replication, pathogenesis, sequencing technology to perform # 95(WYVK\J[PVUHUKWHJRHNPUN Paclik D*, Baßler K*, et al., Schultze JL , criptome analysis, in combination with linked to recurrent infections. We have and evolution. On the one hand, a parallel analysis of the kinetics Aschenbrenner AC#, Li Y#, Nattermann Nucleic Acids Research 46(9):559, J#, Sawitzki B#, Saliba AE#, Sander LE#, in vivo models and tissue engineering, revealed a spectrum of functional doi:10.3389 we investigate the interaction of of translation initiation. In these Deutsche COVID-19 OMICS Initiative are a powerful approach to understand host response states to growing and these functional RNA structures with experiments, we transcribe and tether (DeCOI) (2020) :L]LYL *6=0+  PZ the heterogeneity inherent to the UVUNYV^PUNIHJ[LYPH"ZWLJPÄJHSS`^L Ferhadian D, Contrant M, Printz- proteins, small molecules, or other 95( [V HU 0SS\TPUH ÅV^JLSS PU H ^H` THYRLKI`HK`ZYLN\SH[LKT`LSVPKJLSS infection process. These approaches have discovered that macrophages Schweigert A, Smyth RP, Paillart nucleic acids to identify novel antiviral that couples sequencing information compartment. JC, Marquet R (2018) :[Y\J[\YHS HUK Cell S0092-8674(20)30992-2 also have the potential to decipher containing growing bacteria become -\UJ[PVUHS 4V[PMZ PU 0UÅ\LUaH =PY\Z targets. On the other hand, we study to a functional readout. With this the host-pathogen microenvironment HU[PPUÅHTTH[VY`JLSSZ6\YKH[HZ\W 95(Z genome architecture in viral particles system, we will study the role of RNA Erhard F#, Baptista MAP, Krammer T, and ultimately resolve the impact of port the emerging idea that bacteria Frontiers in Immunology 9:559 to better understand molecular mech- structure, protein-RNA interactions, Hennig T, Lange M, et al., Saliba AE#, individual infection foci on the disease use host genome plasticity to subvert anisms of viral evolution. and ribosome associated factors Dölken L# (2019) ZJ:3(4ZLX YL]LHSZ Smyth RP, Negroni M, Lever AM, Mak JVYLMLH[\YLZVM[YHUZJYPW[PVUK`UHTPJZ progression with unprecedented infected cells. These discoveries have J, Kenyon JC (2018) 95(:[Y\J[\YL( on the rate of translation initiation of PUZPUNSLJLSSZ resolution. By studying Salmonella fostered novel research directions 5LNSLJ[LK 7\WWL[ 4HZ[LY MVY [OL millions of molecules in parallel. Typhimurium and respiratory viruses to integrate scRNA-seq with time ,]VS\[PVUVM=PY\ZHUK/VZ[0TT\UP[` HIGHLIGHTS & OUTLOOK as model pathogens, we develop series and spatial reconstitution of Frontiers in Immunology 9:2097 To better understand the role of RNA AWARDS quantitative methods based on infection foci. In order to capture time- Using high-throughput mutational and dynamics and RNA conformational Mailler E, Bernacchi S, Marquet R, Circulation Research Best Manuscript single-cell transcriptomics to track dependent processes at the single cell Paillart J-C, Vivet-Boudou V, Smyth RP M\UJ[PVUHS WYVÄSPUN ^L OH]L KPZJV] switches during viral replication, we Award (2018) the physiological features of every level, we developed RNA metabolic (2016) ;OLSPMLJ`JSLVM[OL/0=NHN¶ ered a novel RNA motif that regulates are also pioneering the analysis of viral individual pathogen in space and approaches (coined scSLAM-seq) 95(JVTWSL_ the translation of the HIV-1 genome. RNA structure at the single molecule time in association with its host and to reveal the earliest transcriptomic Viruses 8(9):258-267 Our analysis revealed that HIV-1 does level using nanopore technology. to reconstitute the three-dimensional JOHUNLZ H[ [OL ÄYZ[ LUJV\U[LY not regulate translation of its genome Finally, to understand the role of higher environment of infection foci. between host and pathogen. ]PH [OL »<;9 I\[ YH[OLY [OYV\NO order RNA structure on viral replication a short sequence motif within the and evolution we have established a In addition, increasing the sensitivity »<;9>LO`WV[OLZPaL[OH[[OPZTV[PM new methodology called RNA-RNA- of scRNA-seq enables us to capture seq. Using the human ribosome and and describe the transcriptome PUÅ\LUaH ]PY\Z HZ TVKLS Z`Z[LTZ of individual bacterial cells. Such Nucleus A we have shown that RNA-RNA-seq an approach will enable us to also Transcription can identify cis and trans RNA-RNA

reveal the various fates of patho- B Hypothesis: Molecular switch in HIV 5’UTR interactions in cellular contexts. By gRNA RNA export NLUZ PU KPќLYLU[ PUMLJ[PVU MVJP HZ Alternative combining RNA-RNA-seq with state- well as intercellular variability within splicing of-the-art imaging technologies we Translation Packaging communities. Yet, the overarching mRNAs genomic RNA AUG are identifying molecular restrictions to AUG goal will be to interpret these data PBS HIV-1 5’UTR PUÅ\LUaH L]VS\[PVU I` YLHZZVY[TLU[ TAR C Experimental approach within the original spatial context PolyA Our long-term goal is to better 1. Identification of structural signatures regulating HIV-1 translation U5 of the tissue using imaging-based SL1 SL2 SL3 SL4 understand the emergence of novel Mutation approaches. spliced RNAs selection packaged RNA viral strains, such as how potentially packaging Translation Packaging WHUKLTPJ PUÅ\LUaH HYPZLZ MYVT cytoplasmic RNA genetic reassortment in pigs or birds. Structural ribosome changes free selection bound RNA translation RNA

viral proteins Cytoplasm scSLAM-seq captures transcriptional dynamics in infected cells. MCMV, mouse cytomegalovirus; 4sU, (A) HIV-1 genomic RNA is packaged into viruses and translated into proteins. (B) Proposed RNA 4-thiouridine; IAA, iodoacetamide. structural switches. (C) Experimental approach.

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THOMAS DANDEKAR Chair of Bioinformatics, Biocenter

MARKUS ENGSTLER Chair of Cell and Developmental Biology, Biocenter

ULRIKE HOLZGRABE Chair of Pharmaceutical and , Institute for Pharmacy and Food Chemistry

CAROLINE KISKER Chair of Structural Biology, Rudolf Virchow Center for Integrative and Translational Bioimaging (RVZ)

MARCO METZGER Chair of Tissue Engineering and Regenerative Medicine, TERM

JÜRGEN SEIBEL Institute of Organic Chemistry

AUGUST STICH Medical Mission Institute and Clinic for Tropical Diseases, KWM gGmbH

Imagemagmmageage: NicNi olaeolaa AdriaAdAdriadr n

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BIOINFORMATICS MOLECULAR AND PHYSICAL PARASITOLOGY

PROF. THOMAS DANDEKAR PROF. MARKUS ENGSTLER Chair of Bioinformatics, Biocenter Chair of Cell and Developmental Biology, Biocenter [email protected] I +49 931 31 84551 [email protected] I +49 931 31 80060 www.biozentrum.uni-wuerzburg.de/bioinfo www.biozentrum.uni-wuerzburg.de/zeb

RESEARCH INTERESTS We modelled *OSHT`KPH Å\_ HUK RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK SELECTED PUBLICATIONS metabolism during their biphasic SELECTED PUBLICATIONS Yang M, Rajeeve K, Rudel T, Dandekar T A variety of approaches model host- infection course, elementary bodies, Krüger T, Schuster S, Engstler M (2018) Motion is a hallmark of life. We study In the framework of the Physics DFG (2019) *VTWYLOLUZP]L -S\_ 4VKLSPUN pathogen interactions, from individual and reticulate bodies. Comprehen- )L`VUK )SVVK! (MYPJHU ;Y`WHUVZVTLZ TV[PVU VU ]LY` KPќLYLU[ ZJHSLZ MYVT SPP 1726 “Microswimmers”, we VM *OSHT`KPH [YHJOVTH[PZ 7YV[LVTL molecules to metabolic pathways, as sive Flux Modeling of the *OSHT`KPH on the Move. molecules to organelles to cells are looking at the amazing diversity HUK X9;7*9 +H[H 0UKPJH[L )PWOHZPJ well as systems biology, modelling trachomatis life cycle was based on Trends in Parasitology 34(12):1056- and beyond. Our model system is of trypanosome morphotypes in 4L[HIVSPJ +PќLYLUJLZ )L[^LLU ,SL 1067 TLU[HY`)VKPLZHUK9L[PJ\SH[L)VKPLZ regulatory networks and the dynamics selected proteome data by elementary the African trypanosome, a deadly [OL [ZL[ZL Å` LPZZ,3€ўLY1Dandekar T (2019) and metabolic networks as well as [YHUZTPZZPVU >P[O [OL 3€ўLY NYV\W J, Brennich M, Carrington M, Smith times, trypanosomes are covered behind the dramatic transitions (ZWLYNPSS\Z M\TPNH[\Z *OHSSLUNLK I` NLULYH[PUN KPќLYLU[ HUK ZWLJPÄJ we studied how (ZWLYNPSS\ZM\TPNH[\Z A-S, Fenz S, Kisker C, Engstler M with a dense coat of variant surface between solitary and collective motion /\THU +LUKYP[PJ *LSSZ! 4L[HIVSPJ HUK (2017) :[Y\J[\YHSIHZPZMVY[OLZOPLSKPUN 9LN\SH[VY`7H[O^H`9LZWVUZLZ;LZ[PM` biological models of metabolism is challenged by human dendritic cells. M\UJ[PVU VM [OL K`UHTPJ [Y`WHUVZVTL glycoproteins (VSG), encoded by patterns, principles that can also be H;PNO[)H[[SL HUK YLN\SH[PVU PU KPќLYLU[ PUMLJ[PVU There is a tight battle between fungus ]HYPHU[Z\YMHJLNS`JVWYV[LPUJVH[ VSG genes that are subjected to translated to other systems, such as Frontiers in Cellular and Infection processes. (growth pathways, redox protection) Nature Microbiology 2(11):1523-1532 antigenic variation. In order to stay TPJYVIPHSIPVÄSTZ Microbiology 9:168 and the dendritic cells (immune functional during the cell division response pathways supported by lipid Bargul JL, Jung J, McOdimba FA, cycle, the VSG coat has to maintain In addition, our work on trypanosome Naseem M, Bencurova E, Dandekar T 6TVNV *6 (K\UN»H =6 2Y\NLY ; (2018) ;OL *`[VRPUPU(J[P]H[PUN 36. HIGHLIGHTS & OUTLOOK metabolism, Srivastava et al., 2019). Masiga DK, Engstler M (2016) Species- P[Z KLUZP[` HUK Å\PKP[` ;OPZ WYVJLZZ development challenges the dogma -HTPS` 7YV[LPUZ (YL 5V[ 3`ZPUL +LJHY :WLJPÄJ (KHW[H[PVUZ VM ;Y`WHUV requires very accurate control of that life cycle progression to the boxylases. Regarding plant immunity, we found We analyzed antifungal drug and ZVTL 4VYWOVSVN` HUK 4V[PSP[` [V [OL TLTIYHUL HUK WYV[LPU [YHѝJRPUN quiescent stumpy stage requires Trends in Biochemical Sciences that the LOG enzyme is not a lysine vaccine targets by computer model- Mammalian Host. making trypanosomes ideal models a quorum sensing factor. Instead, 43(4):232-236 PLoS Pathogens 12(2):e1005448 decarboxylase but an important ing. In collaboration with the Hans for studying the motion of vesicles and we found that this developmental mediator of cytokinin hormonal res- Knöll Institute, we analyzed in organelles. transition can also occur stochastically, ponses during infection. conidia-containing phagolysosomes during antigenic variation. processes governing immune evasion. We will intensify our studies on the 6UJVS`[PJ ]PY\Z LѝJPLUJ` ^HZ molecular and genetic control of WYLKPJ[LKI`HU[PNLUWYVÄSPUNHUHS`ZPZ trypanosome development and using HUK Ä[[LK )VVSLHU TVKLSZ *LJPS et a biophysical approach of single- al., 2019). Fecal short chain fatty molecule analyses of VSGs on living acids (SCFAs) and SCFA-producing WHYHZP[LZ HUK PU KLÄULK Z`Z[LTZ bacteria in gut microbiome of human we will provide insights into the NAFLD are implied in systemic T-cell dynamics of the trypanosome surface activation and advanced disease, a coat. We will continue our analysis of new IZKF-funded collaboration with a trypanosomes as versatile eukaryotic focus on the mycobiome. microswimmers. One focus will be VU [OL [ZL[ZL Å` WHYHZP[LZ [OL V[OLY Infections are complex multiparametric on the dissemination and annidation processes. To be accessible, omics VM KPќLYLU[ [Y`WHUVZVTL ZWLJPLZ PU data are critical so that bioinformatics their vertebrate hosts. For this, we can shed a light on them analyzing have established human skin tissue changes in metabolism and regulatory models that are naturally infected with networks and the tight interaction [Y`WHUVZVTLZI`[ZL[ZLÅPLZ of attack, response, and defense Overview of the central metabolism of *OSHT`KPH spp. Image adapted from Yang et al., 2019, Frontiers in between host and pathogen. (MYPJHU[Y`WHUVZVTLZ`LSSV^\UKLY[HRLH^LLRZSVUNQV\YUL`[OYV\NO[OL[YHUZTP[[PUN[ZL[ZLÅ`^OPJO Microbiology. is marked by fascinating adaptations to dramatically changing microenvironments.

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MEDICINAL CHEMISTRY STRUCTURE-BASED DRUG DESIGN

PROF. ULRIKE HOLZGRABE PROF. CAROLINE KISKER Chair of Pharmaceutical and Medicinal Chemistry, Institute for Pharmacy and Chair of Structural Biology, Rudolf Virchow Center for Integrative and Food Chemistry Translational Bioimaging [email protected] I +49 931 31 85461 [email protected] I +49 931 31 80381 www.uni-wuerzburg.de/pharmazie www.uni-wuerzburg.de/rvz

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK RESEARCH INTERESTS member of the Bcl-2 family Mcl-1, SELECTED PUBLICATIONS SELECTED PUBLICATIONS have been described as targets of the Berninger M, Erk C, Fuß A, Skaf J, Al- New anti-infective drugs, especially Since Mip has been proven to be Peissert S, Sauer F, Grabarczyk DB, The continuous emergence of wide- chlamydial deubiquitinases ChlaDub1 Momani E, Isreal I, Raschig M, Güntzel P, against protozoa such as malaria, a lethal target in a wide range of Braun C, Sander G, Poterszman spread antibiotic resistances in patho- & ChlaDub2, thus clearly emphasizing Samnick S, Holzgrabe U (2018) trypanosoma, and leishmania, as Gram-negative bacteria, we have A, Egly JM, Kuper J, Kisker C genic bacteria poses a serious risk the importance of these proteins -S\VYPUL >HSR! ;OL 0TWHJ[ VM -S\VYPUL well as Gram-negative bacteria, are established a library of highly active (2020) 0U ;-00/ [OL (YJO KVTHPU VM for current healthcare systems and to chlamydial pathogenicity, which PU 8\PUVSVUL (TPKLZ VU [OLPY (J[P]P[` ?7+ PZ TLJOHUPZ[PJHSS` LZZLU[PHS MVY (NHPUZ[(MYPJHU:SLLWPUN:PJRULZZ urgently needed due to the fact that inhibitors of BpMips and LpMips [YHUZJYPW[PVUHUK+5(YLWHPY new approaches for the treatment is further supported by apparent EJMC 152:377-391 many currently available drugs have by applying structure-based design Nature Communications 11(1):1667 of infectious diseases are urgently NYV^[O KLÄJP[Z PU *OSH+\IKLÄJPLU[ ZPNUPÄJHU[ HK]LYZL LќLJ[Z PU HKKP[PVU in collaboration with D. Begley and required. The obligate intracellular C. trachomatis strains. Encouraged El Hossary E, Schrenzel J, Streker K, to increasing levels of resistance. P. Myler (Seattle), I. Norville (Exeter), as Sauer F, Klemm T, Kollampally RB, bacterium *OSHT`KPH [YHJOVTH[PZ by these results, we pursue the Förstner K, Ohlsen K, Holzgrabe U Tessmer I, Nair RK, Popov N, Kisker C (2018) (UV]LSTLJOHUPZTVMPUHJ[P]H[PVU The latter is especially true for well as T. Inglis and M. Sarkar-Tyson (2019) +PќLYLU[PHS6SPNVTLYPaH[PVUVM[OL is the most frequently diagnosed KL]LSVWTLU[ VM ZWLJPÄJ *OSH+\I HU[PIHJ[LYPHS UP[YV JVTWV\UKZ PU [OL Gram-negative bacteria, such as (Perth). Those inhibitors were also +L\IPX\P[PUHZLZ <:7 HUK <:7  sexually transmitted disease pathogen inhibitors for anti-chlamydial therapy. O\THU WH[OVNLU : H\YL\Z I` V]LY 7ZL\KVTVUHZ2SLIZPLSSH*OSHT`KPH able to inhibit a plethora of the Mip 9LN\SH[LZ;OLPY(J[P]P[PLZ worldwide, and causes more than Molecular Cell 74(3):421-435.e10 L_WYLZZPVU VM H -SH]PUKLWLUKLU[ and 5LPZZLYPH. Blocking the entry of peptidyl-proline- (PPIase) 100 million new cases annually. Our Based on a so-called target hopping UP[YVYLK\J[HZL Antimicrobial Agents Chemotherapy the bacteria, their invasion and their from -YHUJPZLSSH [\SHYLUZPZ @LYZPUPH Ramirez YA, Adler TB, Altmann E, approach focuses on the inhibition approach, pre-existing compounds 62(2):e1510-17 dissemination in the host by targeting WLZ[PZ*V_PLSSHI\YUL[PPand 2SLIZPLSSH Klemm T, Tiesmeyer C, Sauer F, of the chlamydial deubiquitinases MYVT5V]HY[PZKLZPNULK[VZWLJPÄJHSS` virulence factors represent promising WUL\TVUPHL as well as from *OSHT`KPH 2H[OTHU:.:[H[Z`\R(=:V[YPќLY* ChlaDub1 & ChlaDub2 with the aim to target the evolutionary related Adenain Kisker C (2018) :[Y\J[\YHS )HZPZ VM Seufert F, Kuhn M, Hein M, Weiwad M, Z[YH[LNPLZ [V ÄNO[ PUMLJ[PVUZ 4VZ[ [YHJOVTH[PZ 5LPZZLYPH TLUPUNP[PKPZ :\IZ[YH[L 9LJVNUP[PVU HUK *V]HSLU[ establish new tools for the treatment protease, were screened for their Vivoli M, Norville IH, Sarkar-Tyson M, 0UOPIP[PVU VM *K\ MYVT *OSHT`KPH Marshall LE, Schweimer K, Bruhn H, Gram-negative bacteria express & NVUVYYOVLHL, and Leishmania of *OSHT`KPH infections. inhibitory potential against ChlaDub1. trachomatis. 9VZJO 7 /HYTLY 51 :V[YPќLY *( “macrophage infectivity potentiator” tropica. Since ;Y`WHUVZVTHJY\aP are Out of seven tested Adenain inhibitors, ChemMedChem 13(19): 2014-2023 Holzgrabe U (2016) +L]LSVWTLU[ (Mip) proteins that are involved in these also equipped with a Mip protein, two displayed crossreactivity towards Z`U[OLZPZ HUK Z[Y\J[\YLHJ[P]P[`YLSH processes and thus a promising target. we are going to address this enzyme ChlaDub1 with dissociation constants [PVUZOPWZVMPUOPIP[VYZVM[OLTHJYVWOHNL Giroud M, Dietzel U, Anselm L, Banner HIGHLIGHTS & OUTLOOK PUMLJ[P]P[` WV[LU[PH[VY 4PW WYV[LPUZ VM within a consortium of researchers D, Kuglstatter A, Benz J, Blanc JB, in the micromolar range. Despite their 3WUL\TVWOPSHHUK)WZL\KVTHSSLP However, for tropical diseases like ÄUHUJLK I` [OL )4)- P407 ;OL Gaufreteau D, Liu H, Lin X, Stich A, The secretion of dedicated de- TVKLYH[L HѝUP[` ^L Z\JJLLKLK [V Kuhn B, Schuler F, Kaiser M, Brun R, Bioorganic and Medicinal Chemistry malaria, sleeping sickness, and Chagas HPTVM[OLZLZ[\KPLZPZUV[VUS`[VÄUK ubiquitinases by obligate intracellular solve crystal structures of ChlaDub1 24(21):5134-5147 Schirmeister T, Kisker C, Diederich F, disease the situation is even worse potent inhibitors, being useful in the Haap W (2018) 9LW\YWVZPUNH3PIYHY` bacteria plays an intriguing role in JV]HSLU[S` TVKPÄLK I` [OL [^V ILJH\ZLVM[OLSHJRVMLќLJ[P]LKY\NZ therapy of an infection, but also to fully VM /\THU *H[OLWZPU 3 3PNHUKZ! the evasion of the host cell immune compounds. These structures provide The group develops and optimizes \UKLYZ[HUK[OL4PWYVSLPU[OLKPќLYLU[ 0KLU[PÄJH[PVU VM 4HJYVJ`JSPJ 3HJ[HTZ response during an infection. Several the basis to proceed with a structure- AWARDS HZ7V[LU[9OVKLZHPUHUK;Y`WHUVZVTH new anti-infectives, especially by organisms. key components of the cellular immune aided drug design approach. Combin- Bayerischer Verdienstorden (2019) brucei Inhibitors. means of structure- and ligand-based J Med Chem 61(8):3350-3369 response, LN the NF-kappa-B inhibi- ing docking algorithms with molecular drug design. Bisnaphthalimides were found to [VYHSWOH0ы)тHUK[OLHU[PHWVW[V[PJ dynamic simulations, we built upon be active against staphylococci. the cyano-pyrimidine backbones of Interestingly, nitro-substituted com- our two lead structures, generating pounds produced a red color in H SPIYHY` VM TVYL ZWLJPÄJ *OSH+\I multi-resistant staphylococci. In colla- inhibitors. This approach proved to boration with K. Ohlsen (Würzburg), be successful, as the most promising the color changes could be attributed candidate, termed HJR108, displayed to a reduction of the nitro group by H MVSK PUJYLHZL PU HѝUP[` [V^HYKZ a reductase that is overexpressed in ChlaDub1 compared to its precursors. resistant bacteria, revealing a new Several additional cycles of structure- mechanism of resistance. based drug design will be required [V VI[HPU HU PUOPIP[VY ^P[O Z\ѝJPLU[ Furthermore, we are interested to HѝUP[` HUK Z\IZ[YH[L ZWLJPÄJP[` ÄUK UL^ HU[PPUMLJ[P]L Z\IZ[HUJLZ PU towards ChlaDub1 & ChlaDub2. the plant kingdom and to optimize quinolone amides for treatment of trypanosomiasis.

Structure-based design of Mip inhibitors for the treatment of infections by 3LNPVULSSH and)\YROVSKLYPH Close-up view of the ChlaDub1 . The inhibitor is covalently linked to the catalytically active Cys345 via its cyano-pyrimidine based warhead.

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HUMAN 3D TISSUE MODELS TO STUDY CHEMISTRY IN LIVING SYSTEMS HOST-PATHOGEN INTERACTIONS IN

INFECTIOUS RESEARCH PROF. JÜRGEN SEIBEL Institute of Organic Chemistry DR. MARCO METZGER Chair of Tissue Engineering and Regenerative Medicine, TERM [email protected] I +49 931 31 85326 www.chemie.uni-wuerzburg.de/oc [email protected] I +49 931 31 86686 www.term.ukw.de

RESEARCH INTERESTS comprises epithelial and endothelial RESEARCH INTERESTS immune cells. We aim to identify SELECTED PUBLICATIONS layers, a decellularized intestinal SELECTED PUBLICATIONS and validate targets for novel anti- Alzheimer M, Svensson SL, König A major obstacle in infection biology TH[YP_ ZJHќVSK HUK PTT\UL JLSSZ Solger F, Kunz TC, Fink J, Paprotka Our research interests center around infective strategies targeting infectious F, Schweinlin M, Metzger M, is the limited ability to recapitulate Upon Salmonella infection, the model 2 7ÄZ[LY 7/HNLU - :JO\THJOLY - [OL L_WSVKPUN ÄLSK VM NS`JVZJPLUJLZ diseases at the level of modulation of Walles H, Sharma CM (2020) (;OYLL human disease trajectories in mimics human gastroenteritis, in that it Kleuser B, Seibel J, Rudel T (2020) A sphingolipids, and natural products sphingolipid metabolism. As a long- +PTLUZPVUHS 0U[LZ[PUHS ;PZZ\L 4VKLS traditional cell culture and animal restricts the pathogen to the epithelial 9VSLVM:WOPUNVZPULPU[OL0U[YHJLSS\SHY including the development of chemical [LYT WLYZWLJ[P]L YH[PVUHSS` KLÄULK 9L]LHSZ -HJ[VYZ HUK :THSS 9LN\SH[VY` :\Y]P]HSVM5LPZZLYPHNVUVYYOVLHL 95(Z 0TWVY[HU[ MVY *VSVUPaH[PVU >P[O models, which impedes the translation compartment, an advantage over Frontiers in Cellular and Infection and enzymatic syntheses, biocata- synthetic sphingolipid analogues Campylobacter jejuni. of basic research into clinics. Our existing mouse models. Application of Microbiology 10: 215 lysis, protein engineering, and drug or metabolizing enzymes will be PLoS Pathogens 16(2):e1008304 research interest is to apply state- dual transcriptome sequencing to the delivery. Our motivations arise from evaluated for therapeutic options in of-the-art tissue engineering tech- Salmonella-infected model revealed Ortiz-Soto ME, Ertl J, Mut J, Adelmann J, the challenge of understanding KPќLYLU[PUMLJ[PV\ZKPZLHZLTVKLSZ Schulte LN, Schweinlin M, Westermann Le TA, Shan J, Teßmar J, Schlosser A, AJ, Janga H, Santos SC, Appenzeller S, niques, including the use of novel the communication of epithelial, Engels B, Seibel J (2018) 7YVK\J[ fundamental molecular mechanisms Walles H, Vogel J, Metzger M (2020) An biomaterials, dynamic culture, and co- endothelial, monocytic, and natural VYPLU[LKJOLTPJHSZ\YMHJLTVKPÄJH[PVU of life and direct them. Metabolic labeling of cell surfaces (K]HUJLK /\THU 0U[LZ[PUHS *VJ\S[\YL culture settings, allowing the study of killer cells among each other and with VM H SL]HUZ\JYHZL :HJ) ]PH HU LUL and in cells was established in 4VKLS 9L]LHSZ *VTWHY[TLU[HSPaLK the underlying cellular and molecular the pathogen (cooperation with Prof. type reaction. order to study and characterize cell /VZ[ HUK 7H[OVNLU :[YH[LNPLZ +\YPUN Chemical Science 9(24):5312-5321 :HSTVULSSH0UMLJ[PVU mechanisms involved in distinct Jörg Vogel, Würzburg). Our results HIGHLIGHTS & OUTLOOK signaling and cell-cell interactions to mBio 11(1):e03348-19 infectious diseases. Of particular suggest that Salmonella uses its type Becam J, Walter T, Burgert A, Schlegel J, L_HTPUL PUÅHTTH[PVU HUK PUMLJ[PVU interest are models representing III secretion systems to manipulate Sauer M, Seibel J, Schubert-Unkmeir A :WOPUNVSPWPKZ PU PUMLJ[PV\Z KPZLHZLZ! processes. Carbohydrates and Martins Gomes SF, Westermann AJ, human barrier organs such as the :;(;KLWLUKLU[ PUÅHTTH[VY` YL (2017) (U[PIHJ[LYPHSHJ[P]P[`VMJLYHTPKL Because sphingolipids are major ZWOPUNVSPWPKZ^OPJO^LYLTVKPÄLKI` Sauerwein T, Hertlein T, Förstner KU, HUK JLYHTPKL HUHSVNZ HNHPUZ[ WH[OV Ohlsen K, Metzger M, Shusta EV, gastrointestinal tract, blood-brain sponses locally in the epithelium NLUPJ5LPZZLYPH. components of membranes, sphingo- introducing an azide or alkyne group Kim BJ, Appelt-Menzel A, Schubert- barrier, the respiratory tract, and the without accompanying alterations 6FLHQWLðF5HSRUWV 7(1):17627 lipid biosynthesis and metabolism passed the natural sphingolipid and Unkmeir A (2019) 0UK\JLK 7S\YPWV[LU[ skin, which pose the main contact in the endothelial compartment. Our and availability of their signaling inert carbohydrate biosynthetic pathways :[LT *LSS+LYP]LK )YHPU ,UKV[OLSPHS surface for pathogenic microbes. approach promises to reveal further )LY[SLќAPLZJOHUN 5 )LJOVSK 1 or bioactive species substantially and were incorporated into the *LSSZ HZ H *LSS\SHY 4VKLS [V :[\K` O\THUZWLJPÄJ PUMLJ[PVU Z[YH[LNPLZ Grimm C, Reutlinger M, Schneider P, HќLJ[ [OL IPVWO`ZPJHS WYVWLY[PLZ post-translational glycan patterns of 5LPZZLYPHTLUPUNP[PKPZ0UMLJ[PVU Schneider G, Seibel J (2017) ,_WSVYPUN Frontiers in Microbiology 10:1181 employed by Salmonella (Fig. Panel C) [OLZ[Y\J[\YHSZWHJLVMNHSLJ[PUSPNHUK of membranes and the subcellular proteins and sphingolipid metabolism. HIGHLIGHTS & OUTLOOK and other gastrointestinal pathogens interaction. redistribution of receptors and Kress S, Baur J, Otto C, Burkard N, such as Helicobacter pylori and ChemBioChem 18(15):1477-1481 signaling complexes. *OLTPJHS IPVVY[OVNVUHS WVZ[[YHUZSH Braspenning J, Walles H, Nickel J, Our 3D intestinal tissue model Campylobacter jejuni (cooperation [PVUHS WYV[LPU TVKPÄJH[PVU  PUOPIP[VY Metzger M (2018) ,]HS\H[PVU VM H 4PUPH[\YPaLK )PVSVNPJHSS` =HZJ\SHYPaLK was used to study human enteric with Prof. Cynthia Sharma, Würzburg; This may essentially regulate KLZPNU!Site directed mutagenesis has :JHќVSKPU]P[YVHUKPU]P]V infections at a level of detail that is Fig. Panel C). pathogen uptake and handling been used to reshape proteins in their 6FLHQWLðF5HSRUWV8(1):4719 not achieved by conventional two- at a cellular and organismic level function. We investigate bioorthogonal dimensional monocultures. Our model Other research highlights comprise as well as survival and activity of JOLTPJHS [`YVZPUL TVKPÄJH[PVU ]PH our iPSC-derived human blood-brain- the Ene-reaction which seems to barrier (BBB) model to study infection be an attractive strategy especially pathways of 5LPZZLYPH TLUPUNP[PKPZ MVY [HPSVYPUN [OL ZJHќVSK VM LUa`TLZ (cooperation with Prof. Alexandra while extending the canon of natural Schubert-Unkmeir, Würzburg; Fig. amino acids. In addition to the Panel B), which causes diseases such WYV[LPU TVKPÄJH[PVU ^L HSZV MVSSV^ as meningitis and sepsis. Our primary ligand/inhibitor design of proteins. human upper airway tissue models One example is galectins, a protein were used to study interactions with family that has recently become a )VYKL[LSSH WLY[\ZZPZ (cooperation promising source of cancer research, with Prof. Roy Gross, Würzburg; Fig. such as galectin-1, which sits on the Panel A). After infection, we observed surface of all human cells; on tumor severe epithelial damage, such as cells, however, it occurs in enormous cellular extrusions and impaired quantities, making it an interesting barrier integrity. Currently this model is target for diagnostics and therapy. also used in re-purposing compound *VTWSL_ Z\NHY TVSLJ\SLZ ZWLJPÄJHSS` screens with respect to the current binding to the tumor protein Galectin-1 COVID-19 pandemic. are designed, which could help to recognize tumors at an early stage and 3D in vitro models of (A) human airway mucosa, (B) iPSC-derived BBB, and (C) the human gut. Images Functional sphingolipids visualized in herpes infection. to combat them in a targeted manner. by M. Steinke (A), A. Appelt-Menzel (B), M. Schweinlin (C, Salmonella), M. Alzheimer (C, Campylobacter)

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TROPICAL MEDICINE

PROF. AUGUST STICH Medical Mission Institute and Clinic for Tropical Diseases, KWM gGmbH [email protected] I +49 931 791 2821 www.kwm-missioklinik.de/fachabteilungen/tropenmedizin

RESEARCH INTERESTS HIGHLIGHTS & OUTLOOK SELECTED PUBLICATIONS Giroud M, Dietzel U, Anselm L, Banner D, Tropical Medicine is a multisectorial As part of the daily clinical routines, Kuglstatter A, Benz J, Blanc JB, ÄLSK[OH[JVTWYPZLZVM[YH]LSTLKPJPUL our department has managed the Gaufreteau D, Liu H, Lin X, Stich A, diagnosis, and treatment of diseases diagnosis and care of patients with et al. (2018) 9LW\YWVZPUN H 3PIYHY` in hot climates, rare infections, migrant rare infectious diseases like tularaemia, VM /\THU *H[OLWZPU 3 3PNHUKZ! 0KLU[PÄJH[PVU VM 4HJYVJ`JSPJ 3HJ[HTZ health, as well as the provision of histoplasmosis, or echinococcosis. HZ7V[LU[9OVKLZHPUHUK;Y`WHUVZVTH medical care in resource-limited We were directly involved in the brucei Inhibitors. regions. It goes far beyond infectious control of the second largest Ebola Journal of Medicinal Chemistry 61(8):3350-3369 diseases, also providing the link to outbreak in history, which took place the new research areas of Global and in the Democratic Republic of Congo. Gertler M, Loik S, Kleine C, et al., Stich Planetary Health. In Colombia we are involved in an A, Butenop J (2018) >LZ[(MYPJH,IVSH EKFS-founded project to combat V\[IYLHR  PTTLKPH[L HUK OHUKZVU Two percent of returning travelers Chagas Disease in indigenous MVYTH[PVU! [OL WYLKLWSV`TLU[ [YHPUPUN WYVNYHT MVY MYVU[SPUL HPK ^VYRLYZ VM seek medical care for symptoms populations. Our work on migrant [OL .LYTHU 9LK *YVZZ V[OLY HPK connected with the exposure to health in Germany is developing a VYNHUPaH[PVUZHUK[OL.LYTHU(YTLK tropical diseases such as malaria comprehensive approach to improve -VYJLZ>\LYaI\YN.LYTHU` Bundesgesundheitsblatt - Gesund- or dengue fever, parasite infections medical care for asylum seekers and heitsforschung - Gesundheitsschutz (LN .PHYKPH PU[LZ[PUHSPZ), or skin to provide their access to health care 61(4):394-403 conditions (LN Larva migrans as a basic human right. In this context cutanea, staphylococcal pyodermia we developed a tool to improve Lingscheid T, Kurth F, Clerinx J, or erysipelas). In the area of migrant compliance and treatment outcome in Marocco S, Trevino B, et al., Stich A, Pongratz P, Grobusch MP, Suttorp health, German clinicians are often migrant patients with tuberculosis. N, Witzenrath M, Hatz C, Zoller T, faced with unfamiliar diseases such as TropNet SchistosomiasisInvestigator leprosy, intestinal helminths, sickle cell During the next years we will intensify Group (2017) Schistosomiasis in ,\YVWLHU ;YH]LSLYZ HUK 4PNYHU[Z! disease, familial Mediterranean fever, our cooperation with African partners (UHS`ZPZ VM  @LHYZ ;YVW5L[ :\Y]LPS or extrapulmonary tuberculosis, some especially in Tanzania, with a strong lance Data. VM^OPJOHYLKPѝJ\S[[VKPHNUVZLHUK focus on schistosomiasis and other American Journal of Tropical require specialized expertise for which parasitic diseases. Together with the Medicine and Hygiene 97(2):567-574 Würzburg has one of the leading Würzburg-based German Leprosy centers in Germany. and Tuberculosis Relief Association, [OL ^VYSK»Z SHYNLZ[ SLWYVZ` YLSPLM organization, and other partners we founded the .LYTHU *LU[LY MVY 4\S[PZLJ[VYPHS-PNO[(NHPUZ[5LNSLJ[LK ;YVWPJHS+PZLHZLZ (DZVT). Our priority in the next years will be to establish a focal point for training, exchange, HUK UL[^VYRPUN PU [OL ÄLSK VM .SVIHS Health.

Patient care during the 2019 Ebola outbreak in DRC.

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immune system to the pathogenesis of fungal infections. C06 NIKLAS BEYERSDORF 4 RESEARCH PROGRAMS These will help to elucidate the complex mechanisms of (Institute for Virology and Immunobiology) fungal infections and identify common principles of their Secreted fungal proteins in immune evasion pathogenesis. The insights gained from these studies will be and pathogenicity CURRENT RESEARCH PROGRAMS OF ZINF MEMBERS applied to develop new therapeutic approaches. To obtain a comprehensive description and understanding of complex invasive fungal infections, a systems biological approach will be taken to complement studies of fungal pathobiology 4.3 4.1 A08 THOMAS DANDEKAR and the response of the immune system. Systems biology (Dept. of Bioinformatics) will help to reveal the structure and dynamics of molecular DFG RESEARCH UNIT 1680 DFG COLLABORATIVE RESEARCH A systems biology perspective of metabolic HUKJLSS\SHYJH\ZLLќLJ[YLSH[PVUZ^P[OPU[OLZLWH[OVNLUPJ CENTER (CRC) / SFB TRANSREGIO 34 and regulatory adaptation of Staphylococcus interactions. The vision of systems biology is the generation UNRAVELLING THE PROKARYOTIC IMMUNE aureus to infection-related conditions of a virtual infection model that enables the prediction of the SYSTEM PATHOPHYSIOLOGY OF STAPHYLOCOCCI IN INFZ01 An integrated view of adaptation of consequences of changing parameters, such as reduced THE POST-GENOME ERA Staphylococcus aureus HJ[P]P[`VMJLY[HPUPTT\ULLќLJ[VYJLSSZVYYLJLW[VYZMVY[OL The CRISPR-Cas system (CRISPR: clustered regularly infection. A detailed knowledge of the infection biology of interspaced short palindromic repeats, Cas: CRISPR- Staphylococcus aureus is a leading cause of bacterial B04 WILMA ZIEBUHR A. fumigatus and C. albicans and the immune response associated) is an adaptive and heritable resistance infection in hospitals worldwide. This microbe is a (Institute of Molecular Infection Biology) mechanisms will provide the basis for better diagnosis and mechanism against foreign genetic elements. It consists prominent example of the current antibiotic resistance Regulation of methionine metabolism in therapy of systemic infections. Due to the involvement of of clusters of repetitive chromosomal DNA in which crisis, one of the major threats to health in the 21st century.  Z[HWO`SVJVJJP!0TWHJ[VUÄ[ULZZHUK]PY\SLUJL [^V]LY`HJ[P]LJSPUPJHSKLWHY[TLU[ZHZ\ѝJPLU[U\TILYVM short palindromic DNA repeats are separated by short However, S. aureus is also a fascinating model organism samples will be available for analysis and greatly contribute spacers, the latter being sequences derived from the to study host-pathogen interactions. Humans are exposed C06 JÖRG VOGEL [V M\SÄSSPUN [OL WV[LU[PHS VM KL]LSVWPUN [OL IHZPJ ZJPLUJL invader. Key players of this prokaryotic immune system [V[OLZLIHJ[LYPHVM[LU^P[OPU[OLÄYZ[OV\YZVMSPML;OLZL (Institute of Molecular Infection Biology) (bench) to the patient (bedside). are the CRISPR RNAs and Cas proteins, the latter of encounters have a multi-faceted outcome, ranging from Post-invasion events in Staphylococcus aureus which show a remarkable degree of diversity and belong symptomless colonization and mild skin infections to life infected host cells – A combined Projects involving ZINF members: [VHWWYV_PTH[LS`KPќLYLU[WYV[LPUMHTPSPLZ-VYTVZ[VM [OYLH[LUPUN KPZLHZL +LZWP[L L_[LUZP]L LќVY[Z PU [OL ÄLSK transcriptomics / proteomics in vivo approach these proteins their functional roles are unclear. ^LZ[PSSSHJRHULќLJ[P]L]HJJPUL[VWYV[LJ[MYVTS. aureus. A02 HERMANN EINSELE & JÜRGEN LÖFFLER The bacterium is equipped with an impressive assortment C11 MARTIN FRAUNHOLZ & THOMAS RUDEL (Dept. of Internal Medicine II) The major goal of the DFG Research Unit 1680 is to VMÄ[ULZZHUK]PY\SLUJLMHJ[VYZPUJS\KPUNH^PKL]HYPL[`VM (Dept. of Microbiology) Interaction of Aspergillus fumigatus with human unravel the CRISPR-Cas system in bacteria and archaea. immune evasive compounds. Intricate regulation networks Host cell death induced by Staphylococcus natural killer cells, dendritic cells, and human While it has some conserved features in prokaryotes, enable it to withstand hostile environmental conditions, aureus and its linkage to phagosomal escape alveolar epithelia bioinformatics analyses suggest the presence of certain such as nutrient limitation, oxidative stress, or anaerobic WYV[LPUJVTWVULU[ZPUJ`HUVIHJ[LYPHHUKZVTLJOSVYVÅL_P conditions. In recent years, S. aureus has also been A03 ANDREAS BEILHACK which otherwise occur exclusively in archaea. Despite recognized as a facultative intracellular pathogen that can (Dept. of Internal Medicine II) the progress made in understanding CRISPR function, persist inside endothelial and epithelial cells and establish a 4.2 In vivo analysis of temporal and spatial disease the structure and function of its key components remain chronic infection. progression and immune cell recruitment unknown. The novel approach of this Research Unit is to DFG COLLABORATIVE RESEARCH during invasive Aspergillus fumigatus and [HRLZL]LUKPќLYLU[IHJ[LYPHSHUKHYJOHLHSVYNHUPZTZ[V The SFB Transregio 34 (Würzburg, Greifswald, Tübingen, CENTER (CRC) / SFB TRANSREGIO 124 Candida albicans infections KLÄUL[OLJVTTVUTHPUMLH[\YLZVM[OL*90:79Z`Z[LT Münster) addresses multiple dimensions and complexities HUK [V \UYH]LS [OL ZWLJPLZZWLJPÄJ \UPX\L Z\IZ`Z[LTZ of this topic by an interdisciplinary approach using new PATHOGENIC FUNGI & THEIR HUMAN HOST: B01 THOMAS DANDEKAR using a comparative approach with the help of mass methodology. It brings together bacteriological and NETWORKS OF INTERACTION - FUNGINET (Dept. of Bioinformatics) spectrometry, crystallography, and bioinformatics. immunological expertise with quantitative biomolecular Modelling interactions between the host and analytics, structural biology, genomics, bioinformatics, The incidence of invasive mycoses due to opportunistic fungal pathogens by combining metabolic Projects involving ZINF members: hematology, and imaging. In the postgenomic era, the M\UNHSWH[OVNLUZOHZPUJYLHZLKZPNUPÄJHU[S`V]LY[OLWHZ[ pathway analysis and evolutionary game theory availability of whole-genome sequences of S. aureus and two decades. This increase in infections is associated with B02 Interaction networks of signaling molecules B02 JÖRG VOGEL its human host has paved the way for comprehensive excessive morbidity and mortality and is directly related to and pathways between the pathogenic fungi (Institute of Molecular Infection Biology) HUHS`ZPZVM[YHUZJYPW[PVUWYVÄSLZWYV[LPUZHUKTL[HIVSP[LZ a growing number of patients at risk of developing serious Aspergillus fumigatus and Candida albicans Alternative functions of the CRISPR-associated 0[PZUV^WVZZPISL[VVI[HPUIPVSVNPJHSÄUNLYWYPU[ZVMIHJ[LYPH fungal infections. Despite this, the current diagnosis of and their human host endonuclease Cas9 and host with unprecedented detail. This opens avenues SPML[OYLH[LUPUN M\UNHS PUMLJ[PVUZ YLTHPUZ KPѝJ\S[ HUK PZ for a new quality in the understanding of cell physiology, often too late. There are only limited options for therapies, C01 CHRISTIAN PÉREZ pathophysiology, and infection biology. The CRC/TRR 34 ^OPJOHYLVM[LUPULќLJ[P]L;OL`LHZ[Candida albicans (ZINF and IZKF) focuses on host-pathogen interaction during S. aureus HUK [OL ÄSHTLU[V\Z M\UN\Z Aspergillus fumigatus are Molecular characterization of Candida albicans 4.4 colonization and infection, progressing from cell culture by far the most important causes of life-threatening mucosal colonization, infection, and systems of increasing complexity to animal models of invasive mycoses in Europe. Both fungi have developed translocation DFG RESEARCH UNIT 2123 infection, and studies with human subjects. T\S[PWSLZVWOPZ[PJH[LKZWLJPÄJHUK\UPX\LWH[OVNLUPJP[` mechanisms, many of which are not well understood. C02 JOACHIM MORSCHHÄUSER SPHINGOLIPID DYNAMICS IN INFECTION Projects involving ZINF members: (Institute of Molecular Infection Biology) CONTROL This CRC/TRR 124 brings together researchers from the Regulation of Candida albicans virulence traits A02 KNUT OHLSEN Friedrich Schiller University and Hans Knöll Institute in by protein kinases Lipid ordered membrane microdomains enriched for (Institute of Molecular Infection Biology) Jena and the ZINF in Würzburg to obtain comprehensive sphingomyelin and sterols are believed to serve as platforms Phosphoproteomic analysis of Staphylococcus insights into the medically important fungi C. albicans and C03 OLIVER KURZAI for the compartmentalization of membrane-associated aureus: Functional characterization of kinases A. fumigatus and their interactions with the human host. (Institute for Hygiene and Microbiology) proteins such as receptors and membrane-proximal  HUKPKLU[PÄJH[PVUVM[OLPYZ\IZ[YH[LZ The aims of the CRC/TRR 124 are to identify pathogenic Intrinsic modulation of neutrophil antifungal signaling components in regulating processes involved in Z03 In vivo imaging of Staphylococcus aureus KL[LYTPUHU[Z ZWLJPÄJ MVY LHJO M\UN\Z HUK PU]LZ[PNH[L activity against Candida albicans cytoskeletal dynamics. As major membrane components, infections the roles of epithelial barriers, the mechanisms of innate sphingolipids and their ceramide metabolites play a key immunity, and potential contributions of the adaptive role in the dynamics of activated membrane microdomains.

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These are implicated in steps decisive for the interaction Z01 JÜRGEN SEIBEL Projects involving ZINF members: ZWLJPÄJHSS`HPTPUN[V\UKLYZ[HUK[OL[YHUZP[PVUVMPTT\UL of a host cell with pathogens such as attachment, (Institute of Organic Chemistry) OVTLVZ[HZPZ [V^HYKZ PUÅHTTH[VY` WH[OVSVNPLZ ;OPZ LU[Y` PU[YHJLSS\SHY [YHѝJRPUN JVTWHY[TLU[HSPaH[PVU HUK Sphingolipid metabolic pathways in infection P01 LARS DÖLKEN & FLORIAN ERHARD includes (1) the interaction between the intestinal regulation of cell autonomous defense. Because immune control by the use of chemically synthesized (Dept. of Virology) microbiota and the mucosal immune system at early responses can also be regulated at the level of sphingolipid  TVKPÄLKZWOPUNVSPWPKZHUKPU[OLLYHVM Integrative analyses of CMV translatomes and life stages and in response to diet and host genotypes, dynamics, this pathway most likely controls elements in sphingolipidomics MHC-I ligandomes (2) microbe-host interactions in the pathophysiological the pathogenesis of infectious diseases where pathogen transition from immune homeostasis to infectious and uptake, spread, and dissemination are counteracted by P09 HERMANN EINSELE JOYVUPJPUÅHTTH[VY`KPZVYKLYZHUK[OLLZ[HISPZOTLU[ host autonomous, innate, and adaptive immune responses. (Dept. of Internal Medicine II) VM TLJOHUPZ[PJ JVUJLW[Z MVY WYLJSPUPJHS LѝJHJ` HUK 4.5  7LYZVUHSPaLKTLKPJPUL¶9PZRZ[YH[PÄJH[PVUHUK risk evaluation of probiotic intervention and fecal The ultimate goal of the Research Unit 2123 is the prevention of HCMV-related disease in [YHUZWSHU[H[PVU PU PUMLJ[PV\Z HUK JOYVUPJ PUÅHTTH[VY` PKLU[PÄJH[PVUVMUV]LS[HYNL[ZHUK[OLKL]LSVWTLU[VM[VVSZ DFG RESEARCH UNIT 2830 transplant patients based on MHC-I ligandomes disorders. Moreover, the SPP 1656 aims to develop for (immuno)therapeutic interventions. Core topics of this infrastructural networks such as a one-core center for the consortium are the regulatory role of sphingolipid dynamics ADVANCED CONCEPTS IN CELLULAR generation of novel germ-free models and three outposts at the host and pathogen level by addressing (1) adhesion, IMMUNE CONTROL OF CYTOMEGALOVIRUS MVYZWLJPÄJL_WLYPTLU[HSHWWSPJH[PVUZ0UHKKP[PVU[OL:77 HJ[P]H[PVUKPќLYLU[PH[PVUHUKLќLJ[VYM\UJ[PVUZVM;JLSSZ 4.6 1656 will strengthen two core centers for metagenomic at a molecular and cellular level as well as in experimental The human cytomegalovirus (HCMV) persistently infects and metabolite analysis with a strong emphasis on the infection models, and (2) pathogen adhesion/invasion, the majority of the world’s population. Its clinical relevance DFG PRIORITY PROGRAM SPP 1617 transfer of standardized methodologies and protocols for [YHѝJRPUNHUKTVK\SH[PVUVMOVZ[JLSSM\UJ[PVUZLZZLU[PHS and socioeconomic impact is large, but commonly sample processing and data analysis. in the control of bacterial pathogens. The research unit underappreciated. While HCMV infection of healthy PHENOTYPIC HETEROGENEITY AND combines expertise in the infection biology of medically individuals is usually subclinical, life-threatening HCMV SOCIOBIOLOGY OF BACTERIAL POPULATIONS Projects involving ZINF members: important pathogens such as measles virus (MV), Neisseria disease is frequent among the immunocompromised. meningitidis, Neisseria gonorrhoeae, and Mycobacterium In particular, hematopoietic stem cell or solid organ The DFG-funded Priority Program SPP 1617 brings CHRISTIAN PÉREZ tuberculosis, with sphingolipid biology in infectious viral and [YHUZWSHU[ YLJPWPLU[Z Z\ќLY MYVT /*4=PUK\JLK [VNL[OLYTPJYVIPVSVNPZ[ZMYVTHSSÄLSKZVMIHJ[LYPVSVN`e.g., (ZINF and IZKF) bacterial disease pathogenesis, as well as T cell biology, pneumonia, colitis, retinitis, or graft rejection followed by infection biology, terrestrial microbiology, biotechnology, Genetic circuits underlying fungal-bacterial interactions in immunotherapy, and macrophage biology. The Research transplant failure. An even larger social burden stems from etc.) with theoreticians from the mathematical and the mammalian intestine

104 105 4 RESEARCH PROGRAMS

Projects involving ZINF members: PUMLJ[PVUZHUKPU[OLWH[OVNLULZPZVMPUÅHTTH[PVUKYP]LU biology, plant physiology, chemistry, biochemistry, Projects involving ZINF members: diseases. These lines of research will identify previously genetics, genomics, as well as applied bioinformatics. MARKUS ENGSTLER unappreciated functions of the immune system and will CHASE BEISEL (Dept. of Cell and Developmental Biology) pave the way for the development of new treatment Projects involving ZINF members: (Helmholtz Institute for RNA-based Infection Research) From solitary swimmers to swarms and back: trypano- Z[YH[LNPLZ PU PUÅHTTH[PVU 9LZLHYJO VU 03*Z OHZ H Functional characterization of extensively self-targeting ZVTLZVU[OLPYQV\YUL`[OYV\NO[OL[ZL[ZLÅ` strong interdisciplinary trajectory far beyond immunology CYNTHIA SHARMA CRISPR-Cas systems in the bacterial plant pathogen because it develops at the interface between the immune (Institute of Molecular Infection Biology) Xanthomonas albilineans system and the biology of organ development as well Exploring small proteins in the foodborne pathogen as tissue homeostasis and repair. The SPP 1937 aims Campylobacter jejuni CHRISTOPH SCHOEN 4.9 to (1) understand the signals and molecular mechanisms HUK*LU[YHS7YVQLJ[A!9PIVZVTL7YVÄSPUN )PVPUMVYTH[PJZ (Institute for Hygiene and Microbiology) JVU[YVSSPUN 03* MH[L KLJPZPVUZ HUK LќLJ[VY M\UJ[PVUZ The CRISPR/Cas system in Neisseria meningitidis and its DFG PRIORITY PROGRAM SPP 1784 (2) determine how ILCs can discriminate between “self“ JÖRG VOGEL potential role in host cell adhesion and “non-self“, (3) understand the role of ILCs in organ (Institute of Molecular Infection Biology) CHEMICAL BIOLOGY OF NATIVE NUCLEIC homeostasis and tissue renewal, and (4) analyze the Functions of small proteins regulated during Salmonella CYNTHIA SHARMA ACID MODIFICATIONS contribution of ILCs for immunity to infections and in the infection (Institute of Molecular Infection Biology) WH[OVNLULZPZVMPUÅHTTH[PVUKYP]LUKPZLHZLZ Mechanisms and functions of endogenous RNA-targeting 5H[\YHS JV]HSLU[ U\JSLPJ HJPK TVKPÄJH[PVUZ MVYT H UL^ by CRISPR-Cas9 in Campylobacter jejuni hidden layer of information in the genetic code beyond the Projects involving ZINF members: classical four-letter alphabet. The Priority Program SPP 4.12 1784 was established to unravel this code. A network GEORG GASTEIGER of researchers with backgrounds in chemical biology, (Institute of Systems Immunology) DFG PRIORITY PROGRAM SPP 2141 4.13 structural biology, enzymology, and bioinformatics aims Tissue-niches and cellular interactions of mouse and to gain a deeper insight into where, how, and why human ILCs at single-cell resolution MUCH MORE THAN DEFENSE: THE MULTIPLE DFG GERMAN-AFRICAN UH[P]L U\JSLPJ HJPK TVKPÄJH[PVUZ VJJ\Y HUK OV^ [OL` FUNCTIONS AND FACETS OF CRISPR-CAS PUÅ\LUJLJLSS\SHYWYVJLZZLZ4VKPÄJH[PVUZHZKLÄULKPU COOPERATION PROJECTS IN [OLWYVNYHTHYLZWLJPÄJHSS`PU[YVK\JLKPU[V[OLU\JSLPJ One of the most exciting breakthroughs in biology in the INFECTIOLOGY acid by cognate enzymes, and do not include chemical 4.11 past decade has been the discovery of the CRISPR-Cas SLZPVUZ+5(VY95(KHTHNLPUÅPJ[LKI`SPNO[YLHJ[P]L Z`Z[LT 0UP[PHSS` PKLU[PÄLK HZ H WYVRHY`V[PJ 95(IHZLK SHARE - STAPHYLOCOCCI IN AFRICA: oxygen species, chemicals, and the like. SPP participants DFG PRIORITY PROGRAM SPP 2002 defense system, it is now known that genome defense is RESISTANCE & EPIDEMIOLOGY address current challenges in the detection, localization, just one of many functions of this molecular machine. Thus, YLJVNUP[PVUHUKM\UJ[PVUVMUH[\YHSS`VJJ\YYPUNTVKPÄJH SMALL PROTEINS IN PROKARYOTES, the prevailing view of CRISPR-Cas as a defense system is The DFG German-African Cooperation program funds tions in RNA and DNA. These goals are further supported AN UNEXPLORED WORLD too narrow as other important cellular processes can be joint research projects between scientists in Germany by a bundle of measures including provisions for central carried out by the CRISPR-Cas system, such as virulence and Africa investigating infectious diseases with a focus UL[^VYRM\UKZMVYHUHS`[PJHSTL[OVKZJY\JPHS[V[OLÄLSK Prokaryotes are highly abundant and diverse regulation, DNA repair, and the regulation of group on neglected infectious diseases, and their social and in particular deep sequencing and LC-MS. organisms living in all ecological niches. They have behavior. In some cases, CRISPR-Cas systems may even economic implications. In its recent global surveillance broad impact on the environment and our health and have completely lost their immune-related functions. At YLWVY[ [OL >/6 OHZ PKLU[PÄLK HU[PTPJYVIPHS YLZPZ[HUJL Projects involving ZINF members: are crucial for biotechnology and the food industry. this time, we have barely begun to understand the full (AMR) of human pathogens as a serious problem To fully understand their versatile lifestyles and exploit biological potential of this system. The newly revealed that threatens the achievements of modern medicine. CYNTHIA SHARMA their metabolic capacities, knowledge about their functions of the CRISPR-Cas system promise exciting AMR strikes all countries worldwide, but in contrast to (Institute of Molecular Infection Biology) biochemical repertoires and regulatory processes biological discoveries and surprising insights into the new industrialized regions, there is a major gap in knowledge 0KLU[PÄJH[PVUHUKM\UJ[PVUHSJOHYHJ[LYPaH[PVUVMWZL\KV is required. Modern genomics and transcriptomics activities and will open several novel avenues of research. about the magnitude of the problem in countries with limited uridine in mRNAs and non-coding RNAs of the bacterial technologies have discovered a wealth of hidden small Thus far, the new CRISPR-Cas functions have primarily YLZV\YJLZ -VY [OL (MYPJHU YLNPVU [OL >/6 PKLU[PÄLK human pathogen Campylobacter jejuni genes containing short open reading frames (sORFs) in been discovered fortuitously and systematic approaches a lack of data particularly on antibacterial resistance many prokaryotic genomes. These sORFs encode small to detect new functions are lacking. (ABR) for many common and serious conditions, such JÖRG VOGEL proteins of <50 amino acids in length and are typically as meningitis, pneumonia and bloodstream infections. (Institute of Molecular Infection Biology) missed by automated gene predictions. Preliminary ;OL:77HPTZ[VÄUKUL^*90:79*HZM\UJ[PVUZ Also, ABR is no longer exclusively a problem in human +PZJV]LY`HUKJOHYHJ[LYPaH[PVUVM95(TVKPÄJH[PVUZPUH studies have shown that these small proteins impact beyond defense using a systematic coordinated health, but is also an issue in veterinary medicine, bacterial model pathogen cellular processes such as energy generation, transport, approach with 21 research groups. A team of scientists agriculture, food safety and in the environment. The term virulence, symbiosis, sporulation, and photosynthesis. MYVTKPќLYLU[KPZJPWSPULZZ\JOHZTPJYVIPVSVN`NLUL[PJZ º6UL /LHS[O» ^HZ YLJLU[S` JVPULK [V YLÅLJ[ [OPZ OVSPZ[PJ They often localize to membranes and can modulate the medical microbiology, biochemistry, biophysics, approach to the problem. In this project, we will focus HJ[P]P[`VMSHYNLYWYV[LPUJVTWSL_LZ;OLZLPUP[PHSÄUKPUNZ bioinformatics, , structural biology, molecular on ABR and its molecular mechanisms in staphylococci 4.10 notwithstanding, the full repertoire and function of this dynamics, single-molecule localization microscopy, in three African regions (North, East, and South) by cellular small proteome, which comprises potentially and single-molecule biochemistry, makes this program adopting the One Health approach. Staphylococci are DFG PRIORITY PROGRAM SPP 1937 hundreds of small proteins in any given prokaryote, truly interdisciplinary. The two major goals of the SPP some of the most common human pathogens. They remains to be uncovered. HYL!;OLPKLU[PÄJH[PVUHUKPU]LZ[PNH[PVUVMUL^ cause a wide range of clinical manifestations, but also INNATE LYMPHOID CELLS CRISPR-Cas functions beyond genome defense using occur as harmless skin commensals in humans as well The Priority Program SPP 2002 aims to unravel this model representatives of archaea and bacteria, and (2) as in animals, and some species transiently survive in The most recently discovered family of innate immune emerging major class of prokaryotic gene products the elucidation of the molecular mechanisms underlying the environment. Staphylococci readily acquire many cells are innate lymphoid cells (ILCs), which contribute to in order to examine the full repertoire, functions, and these novel functions using state-of-the-art methods. The KPќLYLU[ YLZPZ[HUJL NLULZ HUK TL[OPJPSSPUYLZPZ[HU[ the maintenance of tissue homeostasis, the tolerance to functional importance of prokaryotic small proteins. program is supplemented by a public outreach module to Staphylococcus aureus (MRSA) and coagulase-negative food or commensal bacteria, and the immune responses With the overall goal to identify the composition and communicate the science of CRISPR-Cas to society in a staphylococci (MR-CoNS) are among the most common to pathogens. The SPP 1937 aims to establish an characterize the function(s) of the prokaryotic small comprehensible manner and to facilitate the discussion causes of healthcare-associated infections worldwide. interdisciplinary research program that comprehensively proteome this Priority Program exclusively focuses on of controversial issues with the public, such as for human However, MRSA and MR-CoNS also occur outside of investigates ILCs in mouse models and humans by ribosomally synthesized small proteins in prokaryotes. To genome editing applications. medical facilities and are detectable in the community, in providing novel insights into ILCs as guardians of achieve these goals, the SPP fosters an interdisciplinary animal husbandries, as well as in the environment. The tissue homeostasis and repair, in the defense against cooperation of researchers in microbiology, infection occurrence of the same resistance genes in CoNS and

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S. aureus suggests ongoing genetic exchange between environments. The overarching goal of the project is to method has been applied for. Based on these results, Members of the consortium have developed an immune MRSA and other staphylococci, and CoNS may serve as a interfere with the emergence of pathogenic MDROs at an FINAR 2.0 aims to develop and test strategic measures cell-based approach, antigen reactive T cell enrichment reservoir of resistance genes for S. aureus. The suggested early stage and to prevent their dissemination to humans, in agriculture to contain the emergence of resistance as (ARTE), which allows the host-pathogen status to be research aims to develop a comprehensive insight into including transmission into hospitals. well as to further optimize and to multicenter evaluate of precisely determined and used for diagnosis. ART4Fun the molecular epidemiology and molecular resistance the test prototype in a network of diagnostic laboratories. integrates host-pathogen status and clinical epidemiology mechanisms present in staphylococci in Africa. In the Projects involving ZINF members: and veterinary data for an overarching diagnostic and risk ShARE program, medical microbiologists from Egypt, assessment of fungal lung pathologies and to develop Kenya and South Africa work together with molecular WILMA ZIEBUHR 4.15.2 TRANSSECTORAL RESEARCH new therapies and prevention strategies. This project infection biologists from Germany to determine the MRSA (Institute of Molecular Infection Biology) PLATFORM (TRP) involves the engineering of Aspergillus ZWLJPÄJ ; JLSSZ and MR-CoNS clonal lineages currently circulating in Reducing the AMR burden in farm environments: Impact and their evaluation both in vitro and in an in vivo mouse healthcare settings, livestock and the community in the on human commensals and zoonotic pathogens OLIVER KURZAI model of invasive aspergillosis using advanced in vivo three African regions. The project particularly focuses on (Institute for Hygiene and Microbiology) imaging techniques. Clinical samples from patients with elucidating the molecular mechanisms and genetic basis invasive aspergillosis will be acquired and made available of resistance against novel and last resort antibiotics, The Transsectoral Research Platform (TRP) aims to to other consortium members. HZ^LSSHZVU[OLPKLU[PÄJH[PVUVMMHJ[VYZ[OH[KYP]L()9 4.15 strengthen the cooperation of more than 30 partners expression and transfer into MRSA. of InfectControl 2020 and to educate excellent young BMBF INFECTCONTROL 2020 researchers by carrying out transdisciplinary research Projects involving ZINF members: projects. Facing the growing challenges of infectious 4.16 A rapidly increasing threat is arising from new or resistant diseases requires the joined forces of multiple disciplines WILMA ZIEBUHR pathogens and their growing global circulation. This HUK [V JVVWLYH[L H[ L_JLSSLU[ ZJPLU[PÄJ Z[HUKHYKZ 0U BMBF TARGET VALIDATION FOR (Institute of Molecular Infection Biology) [OYLH[ PZ M\Y[OLY HўPJ[LK ^P[O H KYHZ[PJ SHJR VM UL^ an interdisciplinary cooperation between genetics and PHARMACEUTICAL DRUG Molecular epidemiology and LќLJ[P]L KY\NZ HZ ^LSS HZ PUZ\ѝJPLU[ WYL]LU[P]L HUK PUMLJ[PVU IPVSVN` [OL ;97 ^PSS MVY [OL ÄYZ[ [PTL PKLU[PM` mechanisms in staphylococci from various geographic diagnostic possibilities. There is also a great demand for NLUL[PJ WVS`TVYWOPZTZ [OH[ PUÅ\LUJL HU PTT\UL DEVELOPMENT regions in Africa awareness and information, especially regarding patients response to infectious agents. The occurrence of genetic and specialists in health care professions. InfectControl polymorphisms means that the gene in question can vary The steady increase in nosocomial infections and anti- :WLHRLY!(_LS)YHROHNL1LUH:JPLU[PÄJ4HUHNLY! MYVTWH[PLU[[VWH[PLU[HUK[O\ZKPќLYLU[NLULWYVK\J[Z biotic resistance threatens our health worldwide. The Oliver Kurzai) is a consortium of representatives from TH`ILMVYTLKPUWH[PLU[Z^OPJOOH]LHULќLJ[VU[OL sharp decline in newly approved drugs, particularly in the 4.14 enterprises and academia that jointly aims to develop immune response. This research area is groundbreaking area of anti-infectives, represents a great challenge for solutions to these problems on a national and global for closer cooperation between genetics and infection the global health system. Thus, it is urgently necessary to BMBF #1HEALTH-PREVENT level. Proposals are being developed within the scope biology and provides data sets that can be used in develop new, innovative . In the development of the funding program “Zwanzig20 – Partnerschaft für cooperation with other partners - including industry - to of new active substances, the choice of target molecule ONE HEALTH INTERVENTIONS TO PREVENT Innovation“ headed by the Federal Ministry for Education develop individualized therapeutic approaches. against which the medication is directed is of particular ZOONOTIC SPREAD OF ANTIMICROBIAL and Research (BMBF). With InfectControl 2020, a PTWVY[HUJLHZ[OPZKLÄULZ[OLLќLJ[VM[OLJVYYLZWVUKPUN MULTIDRUG-RESISTANT BACTERIAL highly innovative research alliance has been established therapy. In this program, new targets will be validated, MICROORGANISMS that aims to develop and commercially implement new 4.15.3 RAI STUDENTS serving as structures for the development of new drugs. strategies for the early recognition, the control, and #1Health-PREVENT aims to implement suitable inter- Z\JJLZZM\SHWWYVHJOLZ[VÄNO[PUMLJ[PV\ZKPZLHZLZ OLIVER KURZAI Projects involving ZINF members: vention measures to prevent the zoonotic spread of (Institute for Hygiene and Microbiology) bacterial multidrug resistant microorganisms (MDRO) in Projects involving ZINF members: PyrBac: Validation of pyruvate kinase as a novel meta- agriculture, human, and veterinary medicine as well as in Medical students are tomorrows’ prescribers and bolic target to combat antibiotic resistant bacteria the environment. Pursuing a truly One Health approach, 4.15.1 FUNGAL INFECTIONS AND AZOLE ZWLJPÄJHSS` HKKYLZZLK PU 9(0 :[\KLU[Z 0U HU PU[LY the consortium fosters interdisciplinary collaboration RESISTANCE (FINAR & FINAR 2.0) disciplinary team, we develop new teaching tools and KNUT OHLSEN by joining partners from veterinary and human medical education modules to educate future MDs with regard (Institute of Molecular Infection Biology) microbiology, molecular microbiology, as well as from OLIVER KURZAI (coordination) to rational antibiotic use in infections (RAI). We aim to public health and agriculture. #1Health-PREVENT will (Institute for Hygiene and Microbiology) convey the problems of non-rational antibiotic use and The PyrBac project aims to develop novel active answer open epidemiological questions related to zoonotic communication as well as decision making skills that are substances against resistant bacteria for antibiotic therapy. MDRO spread. Furthermore, the program will challenge Mold fungi cause life-threatening infections in immuno- required for rational decisions in antibiotic treatment. The target of the new substances, pyruvate kinase (PK), UV]LSPU[LY]LU[PVUTLHZ\YLZMVY[OLPYLѝJHJ`HUKWYHJ[PJHS compromised patients and high costs. Similar to avian is a key enzyme of bacterial metabolism not captured by feasibility to limit zoonotic MDRO dissemination. species, invasive mycoses are among the most common JVU]LU[PVUHSHU[PIPV[PJZ72OHZYLJLU[S`ILLUPKLU[PÄLKHZ diseases. Despite an increasing number of cases, 4.15.4 ART4FUN a possible target for the development of new antibiotics. Coagulase-negative staphylococci (CoNS) from livestock diagnostic possibilities are still inadequate. Moreover, It is an essential metabolic enzyme that catalyzes the last and livestock environments were recently found to be resistance to important antimycotics has recently Antigen reactive T cells for the diagnosis and therapy and irreversible step of glycolysis. Due to its essentiality and extensively drug-resistant by carrying novel antimicrobial emerged. A possible cause for this is the widespread of fungal-associated diseases in risk patients close networking with other metabolic pathways, PK has a resistance (AMR) genes and displaying uncommon use of similar substances in plant protection. In contrast very low mutation rate, which makes it a promising target phenotypic AMR, including resistance against last resort to bacterial antibiotic resistance, however, the spread HERMANN EINSELE & JÜRGEN LÖFFLER MVY HU[PTPJYVIPHS [OLYHW` :[Y\J[\YHS KPќLYLUJLZ IL[^LLU antibiotics. Little is known about the impact of these of resistance in fungi still seems avoidable. Within (Dept. of Internal Medicine II) the human isoenzymes and bacterial pyruvate kinases low-grade pathogens and their transmission to directly the framework of FINAR, decisive preliminary work provide the opportunity to develop selective inhibitors of exposed humans. Also, their role in the ecological niche OHZ ILLU JHYYPLK V\[ ^OPJO MVY [OL ÄYZ[ [PTL HSSV^Z Aspergillus fumigatus and other fungi cause life-threatening this enzyme, which might be new antibiotics for the control as putative links between the general environmental AMR a systematic analysis of the development of resistant infections in the immunocomromised or allergic reactions of multidrug-resistant strains. First, various substance gene pool and host-colonizing as well as pathogenic A. fumigatus strains in the environment. At the same time, PU WH[PLU[Z PUJS\KPUN [OVZL ^P[O J`Z[PJ ÄIYVZPZ HZ[OTH classes already recognized as suitable are chemically bacteria is poorly understood. In this project, we will the cooperation between the academic partners and and chronic obstructive pulmonary disease. The actual TVKPÄLK HUK [OLPY HU[PTPJYVIPHS HJ[P]P[` PZ KL[LYTPULK ÄSS RUV^SLKNL NHWZ JVUJLYUPUN [OL LWPKLTPVSVN` VM Biotype Diagnostic within the framework of FINAR will degree of fungal-associated pathologies is not entirely The most active substances are then physico-chemically AMR-CoNS among livestock-exposed individuals and result in the availability of a test prototype of a diagnostic clear because fungi are part of our daily environment, characterized and pharmacological and toxicological test several intervention measures (i.e. use of probiotic kit, which, in addition to the molecular detection of THRPUN JVUJS\ZP]L TPJYVIPVSVNPJHS KL[LJ[PVU KPѝJ\S[ properties are examined. At the same time, a sensitive bacteria, alternative housing conditions of animals) A. fumigatus, will also allow for the detection of the most (JJVYKPUNS`J\YYLU[[OLYHWPLZHYLVM[LUUVUZWLJPÄJHUK detection system is established to detect the substances MVY [OLPY LѝJHJ` [V YLK\JL [OL (49 I\YKLU PU MHYT PTWVY[HU[ YLZPZ[HUJL T\[H[PVUZ ( ÄYZ[ WH[LU[ MVY [OPZ delayed, and diagnostic methods are currently not routine. in the organism. The early application of industrial

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standards is intended to ensure that the results are quickly for tissue invasion and infection of human host cells. The approaches to a broad variety of topics regarding overview of the host and pathogen ncRNAs expressed transferred to further development together with the natural substances FK506 and rapamycin bind and inhibit infectious diseases. during infection and how they control pathogenesis, pharmaceutical industry. The project is therefore pursuing MIPs, but at the same time have an immunosuppressive this consortium combines several high-throughput a highly innovative approach to laying the foundations for LќLJ[ 0U [OLPY PUP[PHS MVYT [OL UH[\YHS Z\IZ[HUJLZ HYL Networks involving ZINF members: approaches with single-cell microscopy techniques. new treatment options for infections caused by antibiotic- unsuitable for the treatment of infectious diseases, since The project will shed light on new virulence regulators resistant bacteria. suppression of the human immune system must be $VS0HW1HW 6\VWHPDWLF LGHQWLðFDWLRQ RI DQWLIXQJDO of C. jejuni, which could constitute targets for novel avoided when treating bacteria. drug targets by a metabolic network approach antimicrobial strategies. In addition, the new approaches developed in this project will be applicable for the study TRANsACT: T-box riboswitches as novel antibacterial The aim of this BMBF project is to develop non- THOMAS DANDEKAR of additional human pathogens. Cynthia Sharma is the targets: Validation of RNA-mediated methionine immunosuppressive FK506 analogues as drug-like MIP (Dept. of Bioinformatics) coordinator of this junior consortium. biosynthesis control in staphylococci as tool and inhibitors for the treatment of MIP-dependent pathogens. proof of principle For this purpose, derivatives of FK506 will be synthesized, Fungal infections pose an increasing threat to the immuno- which preferentially bind to the MIP proteins of compromised and limitations in antifungal therapy arise CINOCA: Co-infection as a cause of ovarian cancer WILMA ZIEBUHR & KNUT OHLSEN Legionella pneumophila, Burkholderia pseudomallei, and MYVTUVUZWLJPÄJZ`TW[VTZVMPUMLJ[PVUWVVYKPHNUVZ[PJZ (Institute of Molecular Infection Biology) Trypanosoma cruzi. The MIP inhibitors will be improved and few options for treatment. Current antifungal drugs THOMAS RUDEL Z[LW I` Z[LW I` JOLTPJHS TVKPÄJH[PVUZ ^OPJO ^PSS IL interfere with the fungal cell wall or plasma membrane but (Dept. of Microbiology) Current development of novel antibacterial drugs is supported by structural information gained in the project. ZOV^ SPTP[LK LѝJHJ` ZL]LYL ZPKL LќLJ[Z VY WH[OVNLU ZPNUPÄJHU[S` OHTWLYLK I` H ZOVY[HNL VM ]HSPKH[LK KY\N If successful, promising substances can be generated YLZPZ[HUJL+LZWP[L[OLPYWYVTPZL[VZLY]LHZOPNOS`ZWLJPÄJ The clinical impact of bacteria-virus co-infections and the targets. The TRANsACT project focuses on T-box with which MIPs can be blocked in meaningful cell and antifungal targets, fungal metabolic pathways have been subsequent chronic infections are both poorly understood, riboswitches (TBRS) as novel target structures against a animal models. This should create promising starting widely neglected. Because Aspergillus, the causative WHY[S`K\L[V[OLKPѝJ\S[`PUKYH^PUNJVUJS\ZP]LL[PVSVNPJHS broad range of important Gram-positive human pathogens points for new anti-infective substances. HNLU[VMHZWLYNPSSVZPZHWWHYLU[S`SHJRZZWLJPÄJ]PY\SLUJL links years after the infection. This transnational network such as multiresistant staphylococci and enterococci, factors, its general characteristics such as growth and aims to investigate the contribution of chronic co-infections *SVZ[YPKP\T KPѝJPSL, pneumococci, and mycobacteria. Projects involving ZINF members: tissue penetration strongly correlate with the outcome with human herpes viruses (HHVs) and the intracellular TBRS represent unique bacterial RNA transcription control of infection of a susceptible host. This relies strictly on bacterium Chlamydia trachomatis (Ctr) to the onset of platforms that interact with tRNAs as ligands to regulate ULRIKE HOLZGRABE nutrient acquisition and metabolic turnover and therefore ovarian cancers. Recent epidemiological studies suggest downstream gene expression. They are widespread (Institute for Pharmacy and Food Chemistry) makes biosynthetic pathways a prime target in antimycotic a strong association of ovarian cancers with both agents among Gram-positive bacteria, where they control many Development of MIP inhibitors of the FK506 type for the therapy. The basic concept of this consortium is to explore and only to a minor extent with human papillomavirus, a essential pathways involved in amino acid and tRNA treatment of Trypanosoma cruzi infections the metabolism of the pathogenic species A. fumigatus known etiologic agent of cervical cancer. An important TL[HIVSPZT 0TWVY[HU[S` ;)9: HYL WYVRHY`V[LZWLJPÄJ on a comprehensive scale. Emerging from transcriptome WHYHKPNTZOPM[PUYLJLU[`LHYZUV^ÄYTS`HZZPNUZ[OLVYPNPU and have no counterpart in eukaryotes, rendering these WYVÄSPUNKH[HTL[HIVSPJUL[^VYRYLJVUZ[Y\J[PVU^PSSZLY]L of ovarian cancer to the epithelial lining of the Fallopian tube structures highly selective antibacterial targets. The aim of [VPKLU[PM`M\UNHSZWLJPÄJIPVZ`U[OL[PJWH[O^H`ZHUKRL` (FT), a prime meeting site for chronic, often asymptomatic [OLWYVQLJ[PZ[VKLÄUL[OLZ[Y\J[\YHSJVUZ[YHPU[ZVM;)9: reactions. Predictions for unique enzymes will result in a infections by both HHVs and Ctr. Thus, accumulating functions as targets for future antibacterial compound 4.18 candidate list of genes, the inactivation of which is likely to evidence warrants a careful analysis of the . We employ a staphylococcal methionyl-tRNA- EUROPEAN RESEARCH AREA result in an auxotrophic phenotype based on conditional events by which these pathogens synergize in establishing ZWLJPÄJ;)9:TL[;)9:HZHZ[Y\J[\YLTVKLSHUK\ZL essentiality of the biosynthetic reaction. Phenotypic and their infectious niche and co-operatively promote met-TBRS-mediated control of methionine biosynthesis NETWORKS (ERA-NET) molecular characterization of these genes will culminate malignant transformation. This consortium consists of of S. aureus as convenient conditional system to study in virulence studies to test infectivity in established animal leading European laboratories in the areas of HHVs and TBRS functions in living bacterial cells as well as in animal The aim of ERA-NET is to promote greater coordination and models of aspergillosis. Based on the resulting data Chlamydia research and two highly committed clinical and infection models. The project builds on comprehensive joint calls for proposals for national and regional research JVSSLJ[PVUZ[OLTL[HIVSPJUL[^VYRTVKLS^PSSILYLÄULKPU SME partners. Together with a clinical partner, who has molecular and functional data, already demonstrating that funding programs in strategically important thematic areas an iterative manner to yield further candidates. Essentially, generated an organoid model of human FT cells, in vitro TBRS impairment can indeed abolish bacterial growth. of European research and innovation. To this end, research this systematically applied metabolic network approach studies will be performed. This novel infection model will TRANsACT will move the project from basic research to funding organizations and program managers from EU will yield novel antifungal drug targets based on the provide the basis for in-depth genomic and epigenomic application by generating robust target validation data and TLTILYZ[H[LZHUKHZZVJPH[LKZ[H[LZWVVSÄUHUJPHSHUK metabolism of A. fumigatus that will serve as candidates analyses that will allow tracing the infection-driven events tools that can immediately be used for future compound human resources for the development of joint activities. MVY[OLYHWL\[PJPU[LY]LU[PVU[VÄNO[M\UNHSPUMLJ[PVUZ of host cell transformation on a genomic scale. In concert, screening and preclinical drug development endeavors. ;OPZZ\WWVY[ZHUKPTWYV]LZ[OLHK]HUJLTLU[LѝJPLUJ` this consortium will illuminate the molecular mechanisms HUKLќLJ[P]LULZZVM,\YVWLHUYLZLHYJO by which HHVs and Ctr jointly reprogram human epithelial CampyRNA: Combining high-throughput and single- cells, providing the basis for malignant transformation. cell analyses to study RNA regulators important in the 4.18.1 INFECT-ERA early steps of Campylobacter infection 4.17 eDEVILLI: Early Determinants of DNA-Virus Lytic or Infectious diseases cause tens of thousands of deaths CYNTHIA SHARMA & ANA EULALIO Latent Infection BMBF iMIP each year in Europe. Despite all the measures taken (Institute of Molecular Infection Biology & ZINF Alumna, DEVELOPMENT OF NON-IMMUNOSUPPRES- [V HKKYLZZ PUMLJ[PV\Z KPZLHZLZ KPќLYLU[ MHJ[VYZ OH]L present address: Center for and Cell LARS DÖLKEN SIVE FK506 ANALOGS AS MACROPHAGE contributed to recent challenges: (1) the threat of Biology, University of Coimbra) (Dept. of Virology) INFECTIVITY POTENTIATOR (MIP) INHIBITORS emerging pathogens, (2) mass migration, global travelers, and growth of congested urban slums, (3) mis- and Bacterial infections entail an active interplay between the Severe disease caused by herpes viruses typically does not FOR THE TREATMENT OF LEGIONELLA PNEU- overuse of antibiotics, and (4) co-infection with at virulence factors of a pathogen and the host response. surface during the initial infection of the otherwise healthy MOPHILA, BURKHOLDERIA PSEUDOMALLEI, least two pathogens. Through this initiative, ERA-NET Non-coding RNAs (ncRNAs), including small, regulatory host, but rather when the virus reactivates from latency AND TRYPANOSOMA CRUZI INFECTIONS partners aim to understand all basic aspects of complex RNAs in bacteria and host microRNAs, are increasingly in immunocompromised individuals, such as organ human infection biology questions that are not limited to recognized as important posttranscriptional gene expres- transplant recipients and AIDS patients. Understanding Gram-negative, pathogenic bacteria such as Legionella ZWLJPÄJ WH[OVNLUZ Z\JO HZ JVPUMLJ[PVU [OL JYVZZ[HSR sion regulators during infection. This consortium uses the mechanisms that contain viral infection and push the or Burkholderia and eukaryotic parasites such as between host and pathogens, as well as the relationship Campylobacter jejuni, currently the most common cause virus into latency immediately upon infection may enable Trypanosoma cruzi are responsible for serious infectious between microbial environment and infection. The ERA- of bacterial food poisoning, as a model organism to their use for life-saving preventive and therapeutic diseases such as Legionnaires‘ disease or Chagas NET consortium funds high quality and cutting-edge study the role of host and pathogen ncRNAs during the measures. The eDEVILLI consortium focuses on the disease. The pathogens use the evolutionary conserved transnational and translational research bringing together LHYS`Z[LWZVMPUMLJ[PVUZWLJPÄJHSS`[OLHKOLZPVU[VHUK characterization of the molecular mechanisms that virulence factor “Macrophage Infectivity Potentiator“ (MIP) basic, applied, technology-driven, and clinical research invasion of epithelial cells. To obtain a comprehensive KLÄUL^OL[OLYH+5(]PY\ZPUMLJ[PVU^PSSYLZ\S[PUSH[LUJ`

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or in lytic infection. By combining a systems biology diseases. A new approach based on distinct biological antimicrobials based on CRISPR-Cas immune systems. 37 countries. Each of the trials will have carefully planned approach with cutting edge genetic manipulation of both and metabolic aspects of parasitic helminths will consider ;OLZL Z`Z[LTZ JHU IL WYVNYHTTLK [V ZWLJPÄJHSS` HUK substudies that add value to the experimental design of [OLOVZ[JLSSHUK[OL]PY\Z^L^PSSKLÄUL[OLOVZ[HUK[OL PU WHY[PJ\SHY WHYHZP[LZWLJPÄJ SPWPK IPUKPUN WYV[LPUZ LѝJPLU[S`LSPTPUH[LJLSSZOHYIVYPUNT\S[PKY\NYLZPZ[HUJL the parent protocols. These substudies will investigate viral factors that bind to viral genomes immediately upon and microRNAs. As these molecules are unique to the genes without impinging on resident microbiota. mechanistic questions and evaluate the experimental infection and shape the decision whether an incoming WH[OVNLUZ [OL` M\SÄSS [OL THPU YLX\PYLTLU[ MVY NVVK However, CRISPR antimicrobials remain to be advanced interventions for important secondary outcomes in a virus will trigger the lytic cycle, or if it will remain latent. selective therapeutic targets. Assessment of their cellular from a few proof-of-principle demonstrations to JVZ[LќLJ[P]L^H`;^VVM[OL[YPHSZ^PSSILWYLJLKLKI` expression will help to prioritize targets that are widely LZ[HISPZOLK[OLYHWL\[PJZ[OH[JHULќLJ[P]LS`JVTIH[[OL PU[LYTLKPH[LZPaL]HUN\HYKZ[\KPLZ[VYLÄULWYV[VJVSZMVY expressed, including in the key stem cell population. most pressing pathogens. The aim of CRISPRattack larger scale investigation, e.g., to estimate parameters for The Nice Bug: Commensalism versus disease – The uniqueness/divergence of several miRNAs and their is to advance this antimicrobial platform to selectively ZHTWSLZPaLVY[VTVYLWYLJPZLS`KLÄUL[OLZ[\K`HYTZ Asymptomatic carriage or urosepsis HIPSP[`[VILKL[LJ[LKPUIPVSVNPJHSÅ\PKZHSZVTHRLZ[OLT kill Klebsiella pneumoniae, a major cause of multi-drug WV[LU[PHSUL^ZWLJPÄJIPVTHYRLYZ

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supported the extended use of whole genome sequencing years, the education and vocational training of medical Networks involving ZINF members: Conventional antibiotics generally work against a broad MVY[`WPUNPU,\YVWLHUKHZZPZ[LK[OL,*+*PUP[ZLќVY[Z specialists and students will be expanded within the spectrum of bacterial pathogens. This promotes the [VKLÄULZ[YH[LNPLZMVY,\YVWLHUTVSLJ\SHYZ\Y]LPSSHUJL scope of exchange programs and the development of StressRegNet: Identifying stressor-regulator pairs development of antibiotic resistance and damages our a joint study program within public health. Additionally, involved in bacterial stress response, virulence, WYV[LJ[P]LTPJYVIPV[H^OPJOJHUOH]L\U^HU[LKLќLJ[Z the medical specialization in both places and a close and antibiotic sensitivity using high-throughput on our health. New antibiotics are therefore needed that collaboration within clinical research will be expedited. approaches and machine learning JHUKPYLJ[S`[HYNL[PUKP]PK\HSWH[OVNLUZSLH]PUNILULÄJPHS 4.21 The newly established center will also focus on an bacteria unharmed. In a multidisciplinary approach, the improved medical care of the population in the hospital CYNTHIA SHARMA & ANA RITA BROCHADO Rbiotics project is studying antibiotics based on RNA- WELLCOME TRUST STRATEGIC AWARD in Mwanza as well as an improved community healthcare (Institute of Molecular Infection Biology, ZINF/Dept. of like molecules, so-called peptide nucleic acids (PNAs) in the area around Lake Victoria. Emphasis will be placed Microbiology) that bind to messenger RNA through complementary FLATWORM FUNCTIONAL GENOMICS VU[OLKL]LSVWTLU[VMHT\S[PHWWYVHJOWYVNYHT[VÄNO[ base pairing and can inhibit the production of proteins. INITIATIVE schistosomiasis, a parasitic disease which is widespread Pathogens are constantly exposed to numerous :\JO 95( HU[PIPV[PJZ JHU IL TVKPÄLK [OYV\NO ZPTWSL in the lake zone and associated with high morbidity rates. environmental cues, which can originate from their host, JOLTPJHS TLHUZ [V HJOPL]L LќLJ[P]LULZZ HNHPUZ[ 7HYHZP[PJ ÅH[^VYTZ JH\ZL ZVTL VM [OL TVZ[ JOYVUPJ the microbiome, as well as from food, antibiotics, and LTLYNPUN WH[OVNLUZ HUK JHU IL \ZLK [V ZWLJPÄJHSS` infectious diseases on our planet. The Flatworm Projects involving ZINF members: other drugs. Pathogens employ diverse strategies to attack individual bacterial strains. Functional Genomics Initiative develops game-changing adapt to these continuously changing environments, research tools for the study and manipulation of parasitic MATTHIAS FROSCH (project management  mostly through transcriptional or post-transcriptional Using high-throughput processes and machine learning, ÅH[^VYTZWLJPLZYLZWVUZPISLMVY[OLKL]HZ[H[PUNKPZLHZLZ OLIVER KURZAI (ZJPLU[PÄJJVVYKPUH[PVU) gene expression control. Besides proteins that act Rbiotics will create a digital platform that will enable echinococcosis (hydatid disease) and schistosomiasis (Institute for Hygiene and Microbiology) as global stress regulators at the transcriptional level, YLZLHYJOLYZ[VZWLJPÄJHSS`KLZPNUKY\NTVSLJ\SLZHNHPUZ[ (bilharzia). The initiative will develop transformative small regulatory RNAs (sRNAs) are important players a variety of dangerous pathogens. PNAs have already functional genomics reagents and make them readily that control stress response and virulence at the post- ILLUJVUÄYTLK[VILLќLJ[P]LPUWYLJSPUPJHSZ[\KPLZI\[ available to the academic research community through transcriptional level. In addition to regulation of virulence there are many open questions, for instance about the well-curated North American and European repositories. 4.23 genes or metabolism during host colonization, there is rules for programming such RNA antibiotics, mechanisms :WLJPÄJHSS`[OL`^PSS\ZLL_WLY[PZLPUTVSLJ\SHYIPVSVN` an increasing number of examples where sRNAs can of resistance development, and possible to host cell biology, and parasitology to create transgenic lines BAVARIAN RESEARCH NETWORK impact antibiotic resistance and tolerance. However, the cells and non-targeted members of the microbiome. We VM WHYHZP[PJ ÅH[^VYTZ HZ ^LSS HZ WYPTHY` HUK PTTVY[HS BAYRESQ.NET external cues that trigger many molecular pathways and are pursuing a combination of transcriptome analysis cell lines derived from these pathogens. These reagents regulators are still largely elusive, as well as how these HUKTHJOPULSLHYUPUN[V\UKLYZ[HUK[OLLќLJ[ZVM75(Z will enable helminthologists to keep pace with other NEW STRATEGIES AGAINST MULTI-RESISTANT regulatory cascades impact bacterial virulence and VU IHJ[LYPHS WH[OVNLUZ HUK [V PKLU[PM` LќLJ[P]L 75( more tractable areas of infectious disease biology and PATHOGENS BY MEANS OF DIGITAL sensitivity to antibiotics. candidates. TVYL LќLJ[P]LS` JVU[YPI\[L [V [OL JVU[YVS VM WHYHZP[LZ NETWORKING responsible for chronic human and animal diseases. FUGI Using high-throughput approaches, the StressRegNet ;OLNVHSVM[OL9IPV[PJZWYVQLJ[PZ[VLZ[HISPZOLќLJ[P]L is available online at www.sanger.ac.uk/collaboration/ According to the WHO, antimicrobial resistance currently consortium aims to explore, which chemical signals PNA candidates for important clinical pathogens by ÅH[^VYTM\UJ[PVUNLUVTPJZPUP[PH[P]LM\NP poses the greatest long-term threat to human health (stressors) trigger pathways responsible for controlling characterizing the molecular basis of PNA activity HUK ^LSSILPUN 4HU` YLZLHYJO LќVY[Z ^VYSK^PKL HYL bacterial adaptation to the host and to antibiotics and resistance development through the systematic Projects involving ZINF members: focusing on this issue. The Bavarian research network in the two major human pathogens Salmonella and analysis of high-throughput data. The knowledge gained bayresq.net builds on novel approaches within basic Campylobacter. Identifying such stressors will help from these studies will form the basis for future logical KLAUS BREHM research to address and counteract the development unravel the extent of cross-talk (epistasis) between design of RNA antibiotics to use against multi-drug (Institute for Hygiene and Microbiology) and spread of resistance in infectious pathogens. KPќLYLU[ZLUZPUNHUKHKHW[H[PVUTLJOHUPZTZPUIHJ[LYPH resistant pathogens and for editing the microbiome. The Functional genomics in Echinococcus multilocularis The central idea of the program is in gaining a deeper and expose unknown bacterial “Achilles heels”, such as development of programmable antibiotics will have major understanding of the processes, which take place during virulence or antibiotic sensitivity pathways, as targets for implications for the treatment of bacterial infections: as infection/colonization as well as the interactions between novel therapeutic intervention. VUS` [OL WHY[PJ\SHY Z[YHPU [HYNL[LK PZ HќLJ[LK PZZ\LZ VM pathogen and host. To achieve this understanding, a resistance development in other bacteria can be avoided. 4.22 common approach based on the systematic use of The StressRegNet project combines bacterial genetics, Additionally, this approach will avoid harming our natural modern data networks among the bayresq.net projects high-throughput screening, and machine learning commensal bacteria. This strategy could also be used ELSE KRÖNER CENTER FOR should enable all users to take immediate advantage of approaches to obtain a general picture of chemical stimuli [V [HYNL[ ZWLJPÄJ M\UJ[PVUZ VM IHJ[LYPH MVY PUZ[HUJL ZV ADVANCED MEDICAL & MEDICAL recently collected data. that trigger bacterial stress responses mediated by sRNAs that resistant bacteria become sensitive to conventional and/or global regulators. To this end, transcriptional antibiotics, or pathogens no longer express toxins. Since HUMANITARIAN STUDIES Through the projects of this research network, Bavaria will reporter libraries of stress-related regulatory sRNAs certain bacterial pathogens are also associated with WÜRZBURG – MWANZA/TANZANIA be strengthened both in the area of life sciences as well in Salmonella and Campylobacter ^PSS IL WYVÄSLK MVY tumorigenesis, RNA antibiotics could also be of interest as data management. At the same time, the groundwork their activity upon exposure to >3,000 host-related for cancer treatment or prophylaxis in the future. To improve the medical care in the region around Mwanza, for the development of improved medical care for future small molecules. Subsequently, the development of which is Würzburg’s partner city in Tanzania, the “Else generations is being set. During the last few years, the machine-learning techniques will allow us to decipher 2Y€ULY-YLZLUP\Z*LU[LYMVY(K]HUJLK4LKPJHS 4LKPJHS Bavarian state government has been able to continuously the implications of these pathways for bacterial sensitivity Humanitarian Studies Würzburg – Mwanza” was founded improve the framework and conditions for the research to antimicrobials. The interdisciplinary approach of the in the beginning of 2020. This research and healthcare landscape in Bavaria and thereby generated optimal StressRegNet consortium enables this unique chemical center will bring together and strengthen the already JVUKP[PVUZ MVY PUUV]H[P]L HUK UV]LS YLZLHYJO ÄLSKZ ;OL genomics approach and the strong interactions between L_PZ[PUN TLKPJHS HUK ZJPLU[PÄJ HJ[P]P[PLZ VM [OL 1\SP\Z area of molecular biology, in particular, has managed to wet-lab scientists and mathematicians will advance Maximilians-University (JMU), the University Hospital rapidly react to international trends as well as pick up infection biology research through digitalization. (UKW), the Medical Mission Institute (MI), and the German HUKHK]HUJLZWLJPÄJRL`[VWPJZYLSL]HU[[V[OLZJPLU[PÄJ Leprosy and Tuberculosis Relief Association (DAHW) community. The research network bayresq.net provides in collaboration with the Catholic University of Health the opportunity to create important conditions for coping Rbiotics: A Digital Approach to Novel RNA Antibiotics and Allied Sciences and the Bugando Medical Center with future challenges within and beyond the borders for Health and Disease in Mwanza in a coordinated and sustainable manner. of Bavaria by sustaining and stimulating basic research The proposed medical-humanitarian development in areas such as immunology, the microbiome, and JÖRG VOGEL, FRANZISKA FABER, & LARS BARQUIST cooperation can build on a longstanding interdisciplinary infectious diseases. (Institute of Molecular Infection Biology, ZINF, Helmholtz JVSSHIVYH[PVUVM[OLPU]VS]LKWHY[ULYZ0U[OLJVTPUNÄ]L Institute for RNA-based Infection Research)

114 115 5 INFRASTRUCTURE 5 INFRASTRUCTURE

5 INFRASTRUCTURE 5.3 5.4 GERMAN CENTER FOR INFECTION INTERDISCIPLINARY CENTER FOR RESEARCH (DZIF) CLINICAL RESEARCH (IZKF) 2018-2019 PROPHYLACTIC APPLICATION OF ESCALATING DOSES OF DONOR-DERIVED CENTRAL MEMORY T-LYMPHOCYTES AFTER ALLOGENEIC 5.1 5.2 HEMATOPOETIC PROGENITOR CELL TRANSPLANTATION TO PREVENT INFECTIOUS NRL FOR MENINGOCOCCI AND THE CONSULTING LABORATORY FOR COMPLICATIONS: A PROSPECTIVE, FIRST IN HAEMOPHILUS INFLUENZAE ECHINOCOCCOSIS MAN, OPEN PHASE I/IIA CLINICAL TRIAL ImImageImagemage:maageaga e: IIZIZKFZZKFKFKF

The IZKF Würzburg organizes the Medical Faculty’s internal research funding, aiming to strengthen clinical research by funding interdisciplinary cooperation between clinicians and scientists. Peer-reviewed application procedures and a transparent fund management are prerequisites for the IZKF’s internal research management. It is steered by three governance boards, which comprise ImageImage:magmage:mmaa ee:: HildeHHiilde Merkerte rtt Image:ge: IHMIHM ImageImamage:e: AdobeAdobAdA obebbee Stotockocockockk the general assembly (meeting of all IZKF members), the executive board that is responsible for the coordination of all programs and the funding decisions, as well as The National Reference Laboratory (NRL) for meningo- The Robert Koch Institute appoints the consulting laboratory In this multicenter clinical study, Hermann Einsele and [OL L_[LYUHS ZJPLU[PÄJ HK]PZVY` IVHYK [OH[ HJJVTWHUPLZ cocci and /HLTVWOPS\Z PUÅ\LUaHL is hosted at the for echinococcosis in Germany every second year for Götz Ulrich Grigoleit (Dept. of Internal Medicine II) the Center’s activities and is involved in the evaluation of Institute for Hygiene and Microbiology at the University consultation, quality management, and development cooperate with clinicians from Munich, Tübingen, and project proposals. The IZKF’s main research areas are of Würzburg and is headed by Ulrich Vogel. The NRL of diagnostic procedures. The Institute for Hygiene and Hannover to improve allogeneic hematopoietic progenitor represented in the IZKF Project Grants. The aim of this has been commissioned by the Robert Koch Institute Microbiology has been hosting the consulting laboratory cell transplantation (alloHPCT). AlloHPCT is a potentially topic-focused funding is to align the Faculty’s existing (RKI) to conduct representative laboratory surveillance of MVYLJOPUVJVJJVZPZZPUJL ;OLJVUZ\S[PUNSHIVYH[VY` curative treatment option for hematological malignancies. ZJPLU[PÄJ WYPVYP[PLZ HUK [V L_WSVYL HUK LUOHUJL UL^ invasive meningococcal disease and invasive infections is an assigned set point laboratory for interlaboratory During the last decade, acute myeloid leukemia (AML) has topics. A close collaboration between clinical and basic caused by /HLTVWOPS\ZPUÅ\LUaHL in Germany, in close comparison tests. It is also involved in the preparation and become a major indication for alloHPCT. However, the research is required to receive funding by the IZKF. After collaboration with the RKI. The NRL data are regularly updating of quality standards for microbiological diagnostic survival of transplanted AML patients is substantially limited – up to three years of IZKF funding, the projects should be TH[JOLK ^P[O Z[H[\[VY` UV[PÄJH[PVU KH[H [V HJOPL]L WYVJLK\YLZ 408 ;OL JVUZ\S[PUN SHIVYH[VY` VќLYZ in particular in older patients – by graft versus host disease transferred to external third-party funds. The IZKF invites comprehensive datasets, which are also reported to the information regarding the prevention and epidemiology (GVHD). In vitro T cell depletion can minimize the risk for WYVWVZHSZL]LY` TVU[OZHUKYLJLP]LZHUH]LYHNLVM European Centre for Diseases Prevention and Control VM KPќLYLU[ [`WLZ VM LJOPUVJVJJVZPZ HZ ^LSS HZ VU [OLPY GVHD, but leads to infectious complications with various  WYVQLJ[ WYVWVZHSZ ^P[O LHJO JHSS

B343 LARS DÖLKEN (Institute for Virology and Immunobiology) Merkel cell carcinoma: model systems for carcinogenesis and therapy of a virus-induced tumor

118 119 5 INFRASTRUCTURE

B369 ANDREAS BEILHACK TWINSIGHT 5.5 (Dept. of Internal Medicine II) Pharmacological destabilization of tumor Under the umbrella of the IZKF, an Integrative Clinician CORE UNIT SYSTEMS MEDICINE  ,*4[VPUJYLHZL[OLLќLJ[P]LULZZVMPTT\UV Scientist College (ICSC) intends to provide a uniform therapeutics and joint platform for all clinician-scientist programs or individual funding schemes in the Faculty of Medicine. One of these funding themes is the newly established The IZKF also funds Clinician scientists, who represent Else Kröner-Forschungskolleg for Translational Twinning an indispensable link between basic sciences, clinical in Systems Immunology and High-throughput Technology research, and patient care. Since both healthcare and (TWINSIGHT), which is funded by the Else Kröner- research are increasingly complex and demanding areas, Fresenius-Foundation and coordinated by professors the IZKF and the Medical Faculty have decided to take Bastian Schilling and Matthias Goebeler (Department of complementary as well as new paths in career support Dermatology, Venerology, and Allergology). With several of young physicians by establishing a rotation PLUS ZINF members as co-applicants (Florian Erhard, Wolfgang ImagImImageImaImagmmamage:mageaageage:ge:ggeee:: AdobAdobeAAdoAdddodobeobeobobeeS S tocktotockooccckk programme, a returnee programme, and a Clinician Kastenmüller, and Cynthia Sharma), there is also a close Scientist programme. The third key instrument of the ZJPLU[PÄJTL[OVKVSVNPJHSHUKZ[Y\J[\YHSSPUR[V[OLA05- IZKF funding is to support the research infrastructure The TWINSIGHT Clinician Scientist College aims to join Next-generation sequencing technologies have at the Medical Faculty. This includes, in particular, the forces to address the problem of an ever-increasing YL]VS\[PVUPaLK[OLZJPLU[PÄJSHUKZJHWLHUKOH]LILJVTL implementation of Core Facilities at the IZKF, in which workload in medicine and the fast pace of technological ubiquitous and essential tools across all areas of important methods, techniques, or special services for development leading to an increasing separation of health research, allowing holistic insights into biological systems. JSPUPJHSYLZLHYJOHYLI\UKSLKLUOHUJLKHUKVќLYLKHZ care and basic sciences. The program is embedded To address the ever-growing demand for generation, a service. within the ICSC Würzburg and enables clinical tandem analysis, and interpretation of such data, the Core Unit teams of physicians in an early career stage to approach :`Z[LTZ 4LKPJPUL *< :`Z4LK ^HZ SH\UJOLK PU  The IZKF supported the following Core Facilities in their own research project by learning and using systems by a joint venture of the Medical Faculty of the University the reporting period: immunological methods and pioneering technologies. It of Würzburg and the Interdisciplinary Center for Clinical also provides a broad complementary curriculum to train Research (IZKF) of the University Hospital Würzburg and is • Core Unit Systems Medicine: nucleic acid and prepare clinician scientists for a career in university located at the Institute of Molecular Infection Biology. The sequencing, bioinformatics, and single-cell analysis. medicine. CU SysMed is a central institution that provides services www.med-uni-wuerzburg.de/cu/sysmed and expertise to researchers at the University and the The TWINSIGHT College supports physicians working on University Hospital in Würzburg as well as external groups • Interdisciplinary Bank of Biomaterials and Data innovative projects using systematic approaches in the by developing, applying, and analyzing a broad range of > YaI\YN PIK^ LZ[HISPZOLK PU  HZ VUL VM ÄLSKZVM[\TV\YPTT\UVSVN`HUKPTT\UV[OLYHW` high-throughput deep sequencing technologies. These Ä]L UH[PVUHS )4)-M\UKLK IPVIHURZ" Z\IHYLH PUÅHTTH[VY`HUKH\[VPTT\ULKPZLHZLZTL[HIVSPJHUK include, for example, mammalian exome sequencing, tissue): safe storage of biomaterials (Contact: cardiovascular immunology, or (4) infection immunology. bacterial and viral genome sequencing, transcriptome Prof. Dr. Roland Jahns, Prof. Dr. Andreas Rosenwald The common goal of the projects is to decipher sequencing (mRNA, ncRNA, total RNA), in addition to www.ukw.de/interdisziplinaere-einrichtungen/ pathophysiologically relevant immunological processes of special sequencing techniques such as dual RNA-seq interdisziplinaere-biomaterial-und-datenbank- such diseases and to improve their therapies on the basis to analyze the transcriptome of host and pathogen in wuerzburg VMTLJOHUPZ[PJYPZRVYILULÄ[IHZLKWH[PLU[Z[YH[PÄJH[PVU parallel, as well as CLIP-seq, RIP-seq, and Grad-seq to VY[VKLÄULWH[PLU[NYV\WZVUHTVSLJ\SHYSL]LS[OH[OH]L study RNA-protein complexes. In collaboration with the • Service Unit for Confocal Microscopy and Flow LP[OLYUVVY]LY`NYLH[ILULÄ[MYVTHWWYV]LK[OLYHWPLZ Helmholtz Institute for RNA-based Infection Research Cytometry-based cell sorting: application of In addition, support is provided for projects that develop (HIRI), a particular focus of the CU SysMed was placed Å\VYLZJLUJL[LJOUPX\LZe.g., systems introduction, and analyze relevant preclinical or in silico models from on the development and application of single-cell RNA support and consulting on experimental designs, and clinical questions. sequencing (scRNA-seq) techniques to address the optional data analysis (Contact: Prof. Dr. Andreas OL[LYVNLUV\Z LќLJ[ VM H WH[OVNLU K\YPUN PUMLJ[PVU VU Beilhack, Prof. Dr. Wolfgang Kastenmüller). For further information please visit www.med.uni- KPќLYLU[ JLSS [`WLZ VU H ZPUN\SHY JLSS SL]LS YH[OLY [OHU H www.virologie.uni-wuerzburg.de/service/imaging wuerzburg.de/izkf/integrative-clinician-scientist- ^OVSLJLSSWVW\SH[PVU;OL[LHTVM[OL*<:`Z4LKWYVÄ[Z college-wuerzburg/else-kroener-forschungskolleg- from a strong alliance between wet-lab scientists and • Interdisciplinary Unit for Personalized Oncology/ twinsight. bioinformaticians as well as close collaborations with Precision Oncology (IUPO): a platform for patient- the local research groups and, consulted by a steering oriented analyses for all kinds of tumors to further committee, it will continue to expand its portfolio of high- KL]LSVW [OL ÄLSK VM WLYZVUHSPaLK [\TVY [OLYHW` I` throughput methods based on requests of the local JVTIPUPUNZJPLU[PÄJHUKJSPUPJHSL_WLY[PZL*VU[HJ[! research community. Prof. Dr. Ralf Bargou, Prof. Dr. Svenja Meierjohann, Prof. Dr. Andreas Rosenwald). For further information please visit the website of the CU SysMed at www.med.uni-wuerzburg.de/cu/sysmed.

For further information please visit the IZKF website at www.med.uni-wuerzburg.de/izkf.

120 121 6 TRAINING THE NEXT GENERATION OF INFECTION BIOLOGISTS 6 TRAINING THE NEXT GENERATION OF INFECTION BIOLOGISTS

6.2 Spokesperson of the GRK 2157: 6 TRAINING THE NEXT GENERATION PROF. DR. THOMAS RUDEL DFG RESEARCH TRAINING GROUP (Dept. of Microbiology) OF INFECTION BIOLOGISTS (GRADUIERTENKOLLEG GRK 2157) 3D INFECT Projects involving ZINF members: 3D TISSUE MODELS FOR STUDYING 01 ANDREAS BEILHACK MICROBIAL INFECTIONS BY HUMAN (IZKF, Dept. of Internal Medicine II) 6.1 Mentoring System PATHOGENS  /VZ[WH[OVNLUPU[LYHJ[PVUZYL]LHSLKI`+ Each doctoral researcher has an individual thesis  OPNOYLZVS\[PVUTPJYVZJVW` GRADUATE SCHOOL OF LIFE committee, which meets with the doctoral researcher SCIENCES (GSLS) VU HU HUU\HS IHZPZ [V TVUP[VY WYVNYLZZ HUK HKQ\Z[ 02 THOMAS RUDEL & THOMAS DANDEKAR research and training activities. Additionally, the doctoral (Dept. of Microbiology, Dept. of Bioinformatics) YLZLHYJOLYZYLWVY[[OLZ[H[\ZVM[OLPYWYVQLJ[^P[OPU[OLPY Host factors required for the initiation and YLZLHYJO NYV\WZ HUK WYVNYHTZ [V L_JOHUNL PKLHZ HUK  WYVWHNH[PVUVMChlamydia trachomatis VI[HPUMLLKIHJR^P[OPU[OLPYWLLYNYV\W infections

Training activities 03 THOMAS RUDEL & ;OL [YHPUPUN HJ[P]P[PLZ JVTWYPZL H TPUPT\T VM  Infectious diseases are still one of the main causes of VERA KOZJAK-PAVLOVIC In 2006, the University of Würzburg launched the OV\YZWLY^LLRHUKJVUZPZ[VMZLTPUHYZQV\YUHSJS\IZ mortality of man. A clear limitation of studying human (Dept. of Microbiology) Graduate School of Life Sciences (GSLS), which was WYVNYHT ZLTPUHYZ TL[OVKZ JV\YZLZ HUK [YHUZMLYHISL WH[OVNLUZPZ[OLSHJRVMHYLSL]HU[PUMLJ[PVUTVKLS;OPZPZ  )HJ[LYPHSHUKOVZ[JLSSMHJ[VYZPTWVY[HU[MVY[OL PUP[PH[LK I` H JVTTVU LќVY[ VM [OL MHJ\S[PLZ VM )PVSVN` ZRPSSZ ^VYRZOVWZ HZ ^LSS HZ YL[YLH[Z HUK PU[LYUH[PVUHS WHY[PJ\SHYS`[Y\LMVYO\THUWH[OVNLUZMVY^OPJOUVHUPTHS invasion and dissemination of Neisseria Medicine, Chemistry and Pharmacy, Physics, and Human conferences. YLZLY]VPY PZ RUV^U :PUJL ZPTWSL JLSS SPULZ JLSS J\S[\YL gonorrhoeae :JPLUJLZ 0[ VќLYZ H OPNOS` PU[LYKPZJPWSPUHY` ^VYR HUK Z`Z[LTZVYHUPTHSZHYLOPNOS`HY[PÄJPHSTVKLSZMVYO\THU study environment for doctoral researchers and ensures Common Graduation Commission WH[OVNLUZ[OL.92HPTZ[VKL]LSVWHUKHWWS`UV]LS 04 ALEXANDRA SCHUBERT-UNKMEIR common graduation standards and rules for doctoral ;OL WHY[PJPWH[PUN MHJ\S[PLZ MVYT H JVTTVU NYHK\H[PVU O\THU[OYLLKPTLUZPVUHS+PUMLJ[PVUTVKLSZIHZLKVU (Institute for Hygiene and Microbiology) researchers. This consists of training that goes beyond JVTTPZZPVU ^P[OPU [OL YLZWLJ[P]L NYHK\H[L ZJOVVS ;OL LUNPULLYLKO\THU[PZZ\LZ;OLVIQLJ[P]LPZ[VLS\JPKH[L[OL  4LUPUNVJVJJHSSPNHUKZHUKTVSLJ\SHY[HYNL[ZYL TLYL ZJPLU[PÄJ L_WLY[PZL HUK LK\JH[PVU VM KVJ[VYHS JVTTPZZPVUPZYLZWVUZPISLMVY[OLJVUMLYYHSVMHSSKVJ[VYHS molecular and mechanistic basis for interactions between  X\PYLKMVYHKOLZPVUHUKWLUL[YH[PVUVM[OLISVVK WYVQLJ[ZHUKPUJS\KLZMVYL_HTWSLNLULYHSSLJ[\YLZHUK degrees within the graduate school. This enforces OVZ[HUKTPJYVILZPUUH[\YHSPUMLJ[PVUZ^P[O[OLSVUN[LYT  JLYLIYVZWPUHSÅ\PKIHYYPLY\UKLYZOLHYZ[YLZZ ZLTPUHYZ TL[OVKZ HUK [YHUZMLYHISL ZRPSSZ JV\YZLZ HZ JVTTVU Z[HUKHYKZ HJYVZZ KPZJPWSPULZ HUK MVZ[LYZ NVHS[VKL]LSVWUL^HU[PPUMLJ[P]LZ[YH[LNPLZ well as annual retreats. The GSLS was funded by the PU[LYKPZJPWSPUHY`JVVWLYH[PVUPUNYHK\H[L[YHPUPUN 05 CYNTHIA SHARMA ¸.LYTHU YaI\YNHYL SECTION INFECTION AND IMMUNITY tract. Engineered 3D human tissues of these entry routes Campylobacter jejuni infections Z[YVUNS` JVTTP[[LK [V Z\WWVY[ [OL .:3: [V HZZ\YL P[Z HYL\[PSPaLKMVYPUMLJ[PVUL_WLYPTLU[Z^P[OZLSLJ[LKO\THU Z\Z[HPUHIPSP[`MVY[OLUL_[ZL]LU`LHYZ;OL.:3:PZ[OL Section Speakers: ZWLJPÄJ TPJYVILZ Chlamydia, Neisseria, Campylobacter, 06 ROY GROSS largest graduate school at the University of Würzburg. PROF. DR. GEORG GASTEIGER Bordetella, Salmonella, Trypanosoma, and measles (Dept. of Microbiology) (Institute of Systems Immunology) ]PY\Z ;OL .92  ^PSS LZ[HISPZO ]HZJ\SHYPaLK [PZZ\L  *OHYHJ[LYPaH[PVUVMOVZ[JLSSYLZWVUZLZHM[LY >P[OPU [OL MYHTL^VYR VM [OL NYHK\H[L ZJOVVS HѝSPH[LK models to address bacterial dissemination, such as seen Bordetella pertussis infection using 2D and 3D YLZLHYJO PUZ[P[\[PVUZ HYL NYV\WLK [VNL[OLY IHZLK VU PROF. DR. JOACHIM MORSCHHÄUSER in gonococcal infection, whereas models for secondary in vitro airway test systems YLSH[LK YLZLHYJO HJ[P]P[PLZ HUK J\YYLU[S` MVYT [OL Ä]L (Institute of Molecular Infection Biology) barriers including human endothelia, 3D human blood brain ¸9LZLHYJO:LJ[PVUZ¸VM[OL.:3:!)PVTLKPJPUL*SPUPJHS IHYYPLYVYK`UHTPJ+*;JLSSPU[LYHJ[PVUZ^PSSILKL]LSVWLK 07 SIBYLLE SCHNEIDER SCHAULIES :JPLUJLZ 0UMLJ[PVU HUK 0TT\UP[` 0U[LNYH[P]L )PVSVN` 6UL VM [OL THQVY MVJHS WVPU[Z VM [OL YaI\YNPZYLÅLJ[LKPU[OL.:3:ZLJ[PVU¸0UMLJ[PVUHUK LUJLWOHSP[PZ TLUPUNVJVJJP [Y`WHUVZVTLZ HUK TLHZSLZ  4LTIYHULHUKWYV[LPUTPJYVKVTHPUZ YLZLHYJOLYZ VM JVSSHIVYH[P]L YLZLHYJO WYVNYHTZ Z\JO 0TT\UP[`¸ H OPNOS` PU[LYKPZJPWSPUHY` HUK PU[LYUH[PVUHSS` ]PY\Z5H[\YHS[PZZ\LZJVUZPZ[VMTVYL[OHUVULJLSS[`WL governing measles virus transmission at entry HZ [OL +-.M\UKLK JVSSHIVYH[P]L YLZLHYJO JLU[LYZ HUK recognized core research area of the university. Within HUKPUKP]PK\HSJLSSZTH`ILOH]LKPќLYLU[S`MYVTJLSSZ^P[OPU  HUKL_P[PU[LYMHJL ;YHUZYLNPVZYLZLHYJO[YHPUPUNNYV\WZHUKJSPUPJHSYLZLHYJO [OL NYHK\H[L ZJOVVS HSTVZ[  WYPUJPWHS PU]LZ[PNH[VYZ TVUVSH`LYZHUKTH`L]LUILTL[HIVSPJHSS`YLWYVNYHTTLK NYV\WZHZ^LSSHZV[OLYJVSSHIVYH[P]LWYVNYHTZM\UKLKI` across more than 20 research centers, institutes, clinics, PUYLZWVUZL[VWH[OVNLULUJV\U[LY;OLZLWYLKPZWVZP[PVUZ 08 JÖRG VOGEL & MARCO METZGER [OL-LKLYHS4PUPZ[Y`VM,K\JH[PVUHUK9LZLHYJO)4)- HUK KLWHY[TLU[Z HZ ^LSS HZ HKKP[PVUHS PUZ[P[\[PVUZ not only require the investigation of microbes during (Institute of Molecular Infection Biology, Dept. of [OL,\YVWLHU

124 125 6 TRAINING THE NEXT GENERATION OF INFECTION BIOLOGISTS

6.3 HUKM\UJ[PVUHSJOHYHJ[LYPaH[PVUVM+<)Z[OH[WSH`JYP[PJHS 6.4 PUMLJ[PVSVN`PTT\UVSVN`OPNOLUKTPJYVZJVW`IPVHUK DFG RESEARCH TRAINING GROUP roles in cancer and infectious diseases. VYNHUPJJOLTPZ[Y`HZ^LSSHZSPWPKHUKWYV[LPUHUHS`[PJZ DFG RESEARCH TRAINING GROUP HUK[OLPYIPVPUMVYTH[PJWYVJLZZPUN (GRADUIERTENKOLLEG GRK 2243) C. Mechanisms of transcriptional control by (de-)ubi- (GRADUIERTENKOLLEG GRK 2581) UBI quitylating enzymes ;HYNL[ WYV[LPU \IPX\P[`SH[PVU HUK KL\IPX\P[`SH[PVU WSH` SPHINGOINF Spokesperson of the GRK 2581: UNDERSTANDING UBIQUITYLATION: U\TLYV\ZYVSLZPU[YHUZJYPW[PVU9LZLHYJOHYLH*MVJ\ZLZ METABOLISM, TOPOLOGY, AND PROF. DR. JÜRGEN SEIBEL FROM MOLECULAR MECHANISMS TO VU[OLJVU[YVSVM[YHUZJYPW[PVU[OYV\NO[OL\IPX\P[`SH[PVU COMPARTMENTALIZATION OF MEMBRANE (Institute of Organic Chemistry) DISEASE Z[H[L VM [^V PTWVY[HU[ NYV\WZ VM [YHUZJYPW[PVU MHJ[VYZ PROXIMAL LIPID AND SIGNALING 4`J MHTPS` TLTILYZ HUK :9,)7Z Z[LYVS YLN\SH[VY` Projects involving ZINF members: COMPONENTS IN INFECTION LSLTLU[IPUKPUNWYV[LPUZ^OPJOHYLJLU[YHSYLN\SH[VYZVM JLSSNYV^[OHUKSPWPKTL[HIVSPZTYLZWLJ[P]LS` 01 LARS DÖLKEN, NIKLAS BEYERSDORFER & SIBYLLE SCHNEIDER-SCHAULIES D. Mechanism of p97 function in health and disease (Institute for Virology and Immunobiology) ;OL (;7HZL W  PZ LZZLU[PHS MVY ]HYPV\Z WH[O^H`Z VM  ;OL5:4HZ]PY\ZLќLJ[VY![HYNL[Z[VWVSVN` the ubiquitin system, because it releases ubiquitylated and functional consequences in T cells ;OLWVZ[[YHUZSH[PVUHSTVKPÄJH[PVUVMWYV[LPUZI`\IPX\P[PU Z\IZ[YH[LZ MVY Z\IZLX\LU[ WYV[LHZVTHS KLNYHKH[PVU VY É\IPX\P[`SH[PVU¸OHZ[HRLUJLU[LYZ[HNLPUL\RHY`V[PJJLSS UVUWYV[LVS`[PJMH[LZ9LZLHYJOHYLH+PZMVJ\ZLKVU[OL 03 NIKLAS BEYERSDORFER & biology. Ubiquitylation triggers the degradation of damaged LS\JPKH[PVUVM[OLTVSLJ\SHYTLJOHUPZTVMW M\UJ[PVUP[Z 0U ZWP[L VM [OL H]HPSHIPSP[` VM WYL]LU[P]L Z[YH[LNPLZ WOLFGANG KASTENMÜLLER WYV[LPUZ JLSS J`JSL YLN\SH[VYZ [YHUZJYPW[PVU MHJ[VYZ HUK JVU[YVSI`YLN\SH[VY`JVMHJ[VYZP[ZT\[H[PVUHSPTWHPYTLU[ PUMLJ[PV\Z KPZLHZLZ JVU[PU\L [V IL H THQVY [OYLH[ (Institute for Virology and Immunobiology, TL[HIVSPJ LUa`TLZ I` [OL : WYV[LHZVTL 0[ ZLY]LZ PU UL\YVKLNLULYH[P]L KPZLHZLZ HUK P[Z THUPW\SH[PVU I` worldwide. Therefore, there is a demand for continuous Institute of Systems Immunology) HZ H ]LYZH[PSL THYR PU THU` UVUWYV[LVS`[PJ WYVJLZZLZ small molecule inhibitors. KL]LSVWTLU[ VM HU[PPUMLJ[P]L VY PTT\UV[OLYHWL\[PJ  :WOPUNVSPWPKZIHSHUJPUN*+-V_W Z\JO HZ +5( KHTHNL YLWHPY YLJLW[VY ZPNUHSPUN HUK Z[YH[LNPLZPUWHY[PJ\SHYMVYJVUKP[PVUZ^OLYLJVU]LU[PVUHS  YLN\SH[VY`HUKLќLJ[VY;JLSSYLZWVUZLZPU endocytosis. Given the multifaceted cellular functions of PU[LY]LU[P]LTLHUZHYLUV[H]HPSHISLWYVOPIP[LKVYMHPS;V chronic viral infections WYV[LPU\IPX\P[`SH[PVUP[PZUV[Z\YWYPZPUN[OH[HIUVYTHSP[PLZ Spokesperson of the GRK 2243: control infectious diseases, novel interventive strategies of the ubiquitin system causally contribute to the PROF. DR. ALEXANDER BUCHBERGER ZOV\SK[OLYLMVYLLќLJ[P]LS`TVK\SH[L! 04 ALEXANDRA SCHUBERT-UNKMEIR WH[OVNLULZPZVMHT\S[P[\KLVMKPZLHZLZPUJS\KPUNJHUJLY (Dept. of Biochemistry) (Institute for Hygiene and Microbiology) neurodegenerative disorders, and infectious diseases. In 1. PUUH[LHUKHKHW[P]LPTT\ULYLZWVUZLZ  9VSLVM:WOPUNVZPULWOVZWOH[LHUK:7 THU`JHZLZOV^L]LYULP[OLY[OLWYLJPZLM\UJ[PVUVM[OL Projects involving ZINF members: and/or  YLJLW[VYZPU[OLWH[OVWO`ZPVSVN`VM HќLJ[LK\IPX\P[PUZ`Z[LTJVTWVULU[PUOLHS[O`PUKP]PK\HSZ 2. [PZZ\L HUK JLSS JVTWHY[TLU[ZWLJPÄJ H\[VUVTV\Z meningococcal meningitis UVYKL[HPSZVM[OLWH[OVNLULZPZMVSSV^PUNP[ZPTWHPYTLU[PZ B1 CAROLINE KISKER TL[HIVSPJ WHYHTL[LYZ HSS VM ^OPJO VWLYH[L [V SPTP[ RUV^U ;OLZL SPTP[LK TLJOHUPZ[PJ PUZPNO[Z JVUZ[P[\[L HU (Rudolf Virchow Center for Integrative and VYPUZVTLPUZ[HUJLZHSZVWYVTV[LIV[OWH[OVNLU 05 OLIVER KURZAI VIZ[HJSL [V [OL KLZPNU VM LѝJPLU[ [OLYHWL\[PJ Z[YH[LNPLZ Translational Bioimaging (RVZ)) ZWYLHKHUK[PZZ\LKHTHNL (Institute for Hygiene and Microbiology) HUK LTWOHZPaL [OL YLX\PYLTLU[ MVY JVU[PU\LK LќVY[Z PU :[Y\J[\YHSHUKM\UJ[PVUHSHUHS`ZPZVM[OL-I^  ;OLYVSLVMZWOPUNVSPWPKZPUPUUH[LPTT\UL basic research. 

126 127 ZINF YOUNG INVESTIGATOR GROUP LEADERS ALUMNI

MEETINGS AND WORKSHOPS (CO)ORGANIZED 7 BY ZINF MEMBERS

APPENDIX SEMINARS AND COLLOQUIA

FUNDING

PUBLICATIONS

DIRECTORY OF PEOPLE ASSOCIATED WITH THE ZINF

128 129 7.1 ZINF YOUNG INVESTIGATOR GROUP LEADERS ALUMNI

7.1 ZINF YOUNG INVESTIGATOR

GROUP LEADERS ALUMNI SVEN HAMMERSCHMIDT Current position: Research at the ZINF: Since the founding of the Research Center for Infectious Diseases, many former Young Investigator group leaders have W3-Professorship at the University of Greifswald, 2003 - 2007 been appointed to highly competitive positions at various universities and industrial companies. Interfaculty Institute of Genetics and Functional Pathogenicity of Streptococcus Genomics pneumoniae

UTE HENTSCHEL HUMEIDA HEIDRUN MOLL Current position: Research at the ZINF: Current position: Research at the ZINF: W3-Professorship at the University of Kiel and the 2004 - 2008 C3-Professorship at the University of Würzburg, 1993 - 1998 GEOMAR Helmholtz Centre for Ocean Research Kiel, Novel antiinfectives Institute of Molecular Infection Biology (IMIB) Pathogenicity of Leishmania Marine Symbioses Research Unit

MICHAEL LANZER GABRIELE PRADEL Current position: Research at the ZINF: Current position: Research at the ZINF: C4-Professorship at the University of Heidelberg, 1994 - 1999 W2-Professorship at the RWTH Aachen University, 2005 - 2011 University Hospital Heidelberg, Pathogenicity of human malaria parasites Cellular and Applied Infection Biology Malaria: Transmission blocking strategies Center for Infectious Diseases, Parasitology Unit

JOACHIM REIDL ANN-KRISTIN MÜLLER Current position: Research at the ZINF: Current position: Research at the ZINF: Group Leader at the University Hospital Heidelberg, 2007 - 2008 Professorship at the University of Graz, 1996 - 2003 Center for Infectious Diseases, Parasitology Unit, Biology of rodent malaria parasites Institute of Molecular Biosciences Virulence of Gram-negative bacteria Project Manager at BioRN Network e.V.

JOACHIM MORSCHHÄUSER SVEN KRAPPMANN Current position: Research at the ZINF: Current position: Research at the ZINF: W2-Professorship at the University Hospital Erlangen, 2007 - 2012 C3-Professorship at the University of Würzburg, 1997 - 2000 Institute of Microbiology, Aspects of Aspergillus fumigatus Institute of Molecular Infection Biology (IMIB) Pathogenicity of Candida Clinical Microbiology, Immunology and Hygiene pathogenicity

KATJA BECKER DANIEL LOPEZ Current position: Research at the ZINF: Current position: Research at the ZINF: C4-Professorship at the University of Gießen, 1999 - 2000 Tenured Scientist Group Leader, Spanish National 2010 - 2015 since 2020 President of the German Research Malarial parasites as targets for the Research Council (CSIC), Spanish National Centre for )HJ[LYPHSJLSSKPќLYLU[PH[PVU Foundation, Deutsche Forschungsgemeinschaft development of antiparasitic drugs Biotechnology (CNB), Dept. of Microbial Biotechnology

KLAUS ERB CYNTHIA SHARMA Current position: Research at the ZINF: Current position: Research at the ZINF: Project Manager, Boehringer Ingelheim Pharma GmbH 1999 - 2004 W3-Professorship at the University of Würzburg, 2010 - 2016 & Co. KG, Dept. of Cancer Immunology & Immune- Immunology of intracellular pathogens Institute of Molecular Infection Biology (IMIB), Deep sequencing approaches to modulation, Adj. Prof. at the University of Würzburg and allergic disorders Chair of Molecular Infection Biology II pathogenesis

MATTHIAS LEIPPE ANA EULALIO Current position: Research at the ZINF: Current position: Research at the ZINF: C4-Professorship at the University of Kiel, 2001 - 2003 Principal Investigator at the University of Coimbra, 2012 - 2017 Institute of Zoology Molecular parasitology Center for Neuroscience and Cell Biology (CNC) Host RNA metabolism

NICOLAI SIEGEL CHRISTOF HAUCK Current position: Research at the ZINF: Current position: Research at the ZINF: W2-Professorship at the Ludwig-Maximilians- 2012 - 2017 W3-Professorship at the University of Konstanz, 2001 - 2006 Universität München, Biomedical Center Munich Trypanosoma gene regulation Cell Biology Pathogen-host communication (BMC), Experimental Parasitology

130130 131131 7.2 MEETINGS AND WORKSHOPS (CO)ORGANIZED BY ZINF MEMBERS

RNA Biology Course 7.2 MEETINGS AND WORKSHOPS Research Centre for Infectious Diseases Chase Beisel, Neva Caliskan ZINF 25th Anniversary Symposium Würzburg, 26 - 28 November 2018 November 14 th, 2018 (CO)ORGANIZED BY ZINF MEMBERS ZINF 25th Anniversary Symposium

10:15 am 25 Years of the ZINF Cynthia Sharma Würzburg, 14 November 2018 MEETINGS AND WORKSHOPS 2018-2019 11:1511 am Robert Koch Lecture Staffan Normark, Karolinska Institute Robert Koch Gold Medal Awardee 2018 th Please note that for meetings and workshops organised by multiple people, only ZINF members are listed. 4 qNMR Summit 2018 Ͳ >ƵŶĐŚƌĞĂŬͲ Ulrike Holzgrabe 1:30 pm Talks by Young Investigators Würzburg, 10 - 11 October 2018 Sina Bartfeld, ZINF Sebastian Geibel , ZINF Christian Perez , ZINF/IZKF 7th International Summer School Infection Biology Guests Franziska Faber , ZINF RNA Biology Course Joint Meeting TR124 “FungiNet” & Invasive Mycoses are welcome! Ana Rita Brochado , Biocentre/ZINF 2018 Chase Beisel, Neva Caliskan in Haematological Malignancies XIII (IMIHM XIII) Thomas Dandekar 2:45 pm Scientific Presentations Würzburg, 9 - 13 December 2019 /LYTHUU,PUZLSL6SP]LY2\YaHP1 YNLU3€ўLY Eric Pamer Würzburg, 17 - 21 September 2018 Würzburg, 27 - 28 May 2019 Memorial Sloan Kettering Cancer Center, NY Ͳ ŽĨĨĞĞƌĞĂŬͲ RNA and Infection Science Slam Joint Meeting TR124 “FungiNet” & Invasive Mycoses 3:45 pm Dirk Brockmann Neva Caliskan Infection & Immunity Short Course, co-organized by Humboldt University/RKI Berlin in Haematological Malignancies XII (IMIHM XII) Würzburg, 25 November 2019 HIRI and IMIB Noam Stern-Ginossar /LYTHUU,PUZLSL6SP]LY2\YaHP1 YNLU3€ўLY Weizmann Institute of Science, Rehovot Franziska Faber, Emmanuel Saliba, Alexander Ͳ ^ŚŽƌƚƌĞĂŬͲ Würzburg, 26 - 27 June 2018

Science Communication Workshop Westermann 5:15 pm Dennis Kopecko Neva Caliskan Würzburg, 8 - 10 May 2019 Combivax, LLC, Silver Spring, MD Symposium der Fachgruppen “Mikrobielle Dirk Haller Würzburg, 14 - 15 November 2019 TU München Pathogenität” (DGHM/VAAM) und “Gastrointestinale Cold Spring Harbor Asia Conference “Bacterial Infektionen” (DGHM) 2018 Venue Institute of Molecular Infection Biology (IMIB) EMBO Workshop “The impact of bacterial infections Infection & Host Defense” Josef-Schneider-Str. 2 / Bau D15 Cynthia Sharma 97080 Würzburg on human cancer” Jörg Vogel Contact: Petra Thomas Bad Urach, 20 - 22 June 2018 Thomas Rudel Suzhou (China), 8 - 12 April 2019 [email protected] Online registration: www.uni-wuerzburg.de/zinf/registration-zinf Berlin, 26 - 29 October 2019 Else-Kröner-Symposium “Translational Immunology 3D Tissue Infection Symposium – From Target To Therapy V” EMBO Symposium “The Non-Coding Genome” Thomas Rudel Andreas Beilhack Jörg Vogel Würzburg, 5 - 7 April 2019 The Würzburg, 12 - 13 April 2018 EMBL Heidelberg, 16 - 19 October 2019 Non-Coding Workshop “Single-cell Biology of Infection” Genome 28th Annual Meeting of the German Society for 8th International Summer School Infection Biology Emmanuel Saliba, Jörg Vogel Parasitology EMBO | EMBL 2019 Würzburg, 28 March 2019 Symposium Markus Engstler th 16 – 19 October 2019 5 JOINT MEETING Invasive Mycoses in Haematological Malignancies Thomas Dandekar Heidelberg | Germany IMIHM XII & CRC / TRANSREGIO 124 Berlin, 21 - 24 March 2018 EMBL Advanced Training Centre “Pathogenic fungi and their human host: Networks Würzburg, 23 - 27 September 2019 Frontiers in Medicinal Chemistry 2019 – Joint of interaction – FungiNet“ conference of the Gesellschaft Deutscher Chemiker Carbohydrate Biocatalysis Symposium AIChE 3rd International Conference on CRISPR and the Deutschen Pharmazeutischen Gesellschaft 28th Annual Meeting of Jürgen Seibel the Society for Virology

Technologies Ulrike Holzgrabe *HVHOOVFKDIWIU9LURORJLH Cuernavaca (Mexico), 18 March 2018 Chase Beisel, Jörg Vogel Würzburg, 24 - 27 March 2019 XQG 'HXWVFKH9HUHLQLJXQJ]XU%HNlPSIXQJ Würzburg, 16 - 18 September 2019 '99 GHU9LUXVNUDQNKHLWHQ Immunology Training Course for the students of the Cell-free TXTL Workshop intended for SPP 2141 GRK 2157, 3D Infect 22nd International Symposium on Signal Transduction students Andreas Beilhack at the Blood-Brain Barriers Chase Beisel Würzburg, 12 - 14 March 2018 Marco Metzger Würzburg, 11 - 13 February 2019 © Congress-Tourismus-Wirtschaft Würzburg l Fotograf A. Bestle Würzburg, 11 - 13 September 2019 14–17 March 2018 28th Annual Meeting of the German Society of :U]EXUJĆ*HUPDQ\ Update chronische Virushepatitis 2019 8QLYHUVLWlW:U]EXUJ Virology (GFV) 2018 Else-Kröner-Symposium “Translational Immunology – Hartwig Klinker Lars Dölken From Target To Therapy VI” Würzburg, 30 January 2019 Würzburg, 14 - 17 March 2018

Andreas Beilhack © 88649465 l JiSign l Fotolia.com Würzburg, 27 - 29 June 2019 Workshop for the Initiation and Development of DGHM 2018 Fachgruppenmeeting Microbial Biotechnological Strategies in Glycoscience Pathogenesis (MPAT) th Childcare 9 Würzburg Meningococci- and Haemophilus Jürgen Seibel Grants Alexandra Schubert-Unkmeir now available LQƃXHQ]DH-Workshop: Meningo meets TB Würzburg, 23 - 24 January 2019 Bochum, 19 - 21 February 2018 Ulrich Vogel Würzburg, 25 June 2019 Workshop & Hands-on Training “RNA-seq data Joint DAAD – ShARE Meeting “Staphylococci and analysis” for the students of the GRK 2157, 3D Infect Antimicrobial Resistance Management” 15th EMGM Congress 2019 Emmanuel Saliba, Cynthia Sharma, Alexander Wilma Ziebuhr Ulrich Vogel Westermann Würzburg, 7 - 9 February 2018 Lisbon (Portugal), 27 - 30 May 2019 Würzburg, 13 - 14 December 2018 The impact of bacterial Update chronische Virushepatitis 2018 Hartwig Klinker infections on human cancer Würzburg, 31 January 2018 26 – 29 October 2019 | Berlin, Germany

132 133 7.3 SEMINARS AND COLLOQUIA

17 April 2018 23 July 2019 7.3 SEMINARS AND COLLOQUIA Mathias Hornef, University Hospital Aachen Mathias Munschauer, HIRI, Würzburg The neonatal window of opportunity: age-dependent Decoding the functions of long non-coding RNAs through factors of enteric host-microbial homeostasis their protein interactomes SEMINARS & COLLOQUIA 2018-2019 06 February 2018 09 July 2019 Rob Lavigne, KU Leuven, BE Daniel Wilson, University of Hamburg Hijacking Pseudomonas: using phage to develop new Antimicrobial peptides as novel ribosome-targeting antibacterial design strategies and biotechnological antibiotics MICROBIOLOGY COLLOQUIUM 29 January 2019 applications 5REHUW)DJDQ8QLYHUVLW\RI6KHτHOG8. 14 May 2019 17 December 2019 *YHJRPUN H KPѝJ\S[ JY`Z[HS ZOLSS! KPZZLJ[PUN :SH`LY 30 January 2018 Chris Hill, University of Cambridge, UK Ilse Jacobsen, University of Jena structure and function Karl Forchhammer, University of Tübingen +LÄUPUN [OL ¸SPJLUJL [V J\[¹! Z[Y\J[\YHS HUK M\UJ[PVUHS Pathogenesis of candidiasis: The impact of bacteria and Prepared for awakening: the resuscitation program of a insights from deconstructing the eukaryotic mRNA 3‘ end fungal virulence factors 15 January 2019 dormant Cyanobacterium processing machinery Man-Wah Tan, Genentech, San Francisco, US 03 December 2019 Inspired by Nature: Engineering natural products and 23 January 2018 30 April 2019 Philippe Bouloc, Institute for Integrative Biology of antibodies to treat infections Birgitta Henriques-Normark, Karolinska Institute, Chris Ponting, University of Edinburgh, UK the Cell (I2BC), Paris, FR Stockholm, SE Post-transcriptional regulation of mitochondrial activity by Competition experiments reveal S. aureus regulatory RNAs 20 November 2018 Pneumococcal interactions with the host noncoding RNAs that cope with antibiotic and iron stresses Gunnar Hansson, University of Gothenburg, SE The MUC2 mucin and the inner mucus layer as an 16 January 2018 05 February 2019 19 November 2019 PUUH[LPTT\ULTLJOHUPZT[OH[PUOPIP[ZPUÅHTTH[PVUHUK Dominique Sanglard, University of Lausanne, CH Noam Stern-Ginossar, Weizmann Institute of Science, Fabrizia Stavru, Institut Pasteur, Paris, FR ulcerative colitis - similarities to chronic lung diseases A journey through fungal cell functions by antifungal drug Jerusalem, IL Mitochondria and intracellular bacteria: how close can resistance mechanisms Post-transcriptional control of host gene expression you get? 06 November 2018 during viral infection John D. MacMicking, Yale University, US 09 January 2018 22 October 2019 Cell-autonomous immunity to infection: the art of self- Martin Simon, University of Saarland 22 January 2019 Margherita Y. Turco, University of Cambridge, UK defense Small RNA pathways in Paramecium: Environmental Peter Nielsen, University of Copenhagen, DK Organoid systems to model the maternal-fetal interface of RNAi by bacterial RNA and non-Mendelian inheritance of A future of genetic antibiotics – antibacterial properties of human pregnancy 23 October 2018 gene expression patterns antisense peptide nucleic acids (PNA)-peptide conjugates Harry Low, Imperial College London, UK 16 July 2019 Architecture of a bacterial type II secretion system 7KRUVWHQ6WDσRUVW8QLYHUVLW\RI7şELQJHQ Sven Hammerschmidt, University of Greifswald ,UNPULLYPUN[VVSZMVYZP[LZWLJPÄJ95(THUPW\SH[PVU The infection dynamics of the pathobiont Streptococcus 10 July 2018 RNA SEMINAR pneumoniae Jörg Overmann, German Collection of Microorganisms 8 January 2019 and Cell Cultures (DSMZ), Braunschweig 10 December 2019 Ciarán Condon, CNRS Paris, FR 02 July 2019 Elucidating novel functions in microbial dark matter Sam Sternberg, Columbia University, US Coupling of transfer RNA and ribsomal RNA maturation Richard Hayward, University of Cambridge, UK Transposon-encoded CRISPR-Cas systems direct RNA- via stringent control Lessons in nuclear remodelling from Chlamydia 26 June 2018 guided DNA integration trachomatis Bernhard Krismer, University of Tübingen 18 December 2018 Bacterial way of life in the human nose - a story about 26 November 2019 Susan Carpenter, University of California, UC Santa 18 June 2019 Staphylococcus aureus and its competitors Markus Landthaler, Max-Delbrück Center for Molecular Cruz, US Jennifer Rohn, University College London, UK Medicine in the Helmholtz Association, Berlin /V^KVSVUNUVUJVKPUN95(ZJVU[YPI\[L[VPUÅHTTH[PVU& The secret life of invasive bacteria: modelling chronic 12 June 2018 Post-transcriptional regulation in cellular space and time urinary tract infection with a novel human organoid Caroline Genco, TUFTS University in Medford and 11 December 2018 platform Somerville, US 12 November 2019 Simone Backes, University of Würzburg Distinct gonococcal gene signatures expressed during Peter Fineran, University of Otago, NZ The roles of small non-coding RNAs during virus infection 04 June 2019 human mucosal infection in men & women CRISPR-Cas regulation and immune mechanisms Ana Rita Brochado, University of Würzburg 27 November 2018 Deciphering antimicrobial drug interactions using high- 05 June 2018 29 October 2019 Blake Wiedenheft, Montana State University, US throughput approaches Gilad Bachrach, Hebrew University of Jerusalem, IL Yang Li, Centre for Individualised Infection Medicine, ,]VS\[PVUHY`V\[JVTLZVM*90:79HU[P*90:79JVUÅPJ[ From tooth to tumor, cancer acceleration by Fuso- Hannover 21 May 2019 bacterium nucleatum+PK`V\ÅVZZ[VKH`& A big data approach for individualised infection medicine: 13 November 2018 Peter Redder, Centre of Integrative Biology (CBI) in translating genetic variation into immune function Demian Cazalla, University of Utah, US Toulouse, FR 29 May 2018 Lessons from viruses: a novel function for Sm-class RNAs RNA decay in Staphylococcus: global scale and molecular Manuel Amieva, Stanford University, US 15 October 2019 detail Should we be looking for the bacterial stem cell Gisela Storz, NIH, Bethesda, US 30 October 2018 compartment? Lessons from Helicobacter pylori Redundancy in regulatory RNA networks Renate König, Paul-Ehrlich-Institute, Langen 07 May 2019 New insights into innate sensing and restriction of HIV-1 Joseph Zackular, University of Pennsylvania, US 15 May 2018 Anna Pyle, Yale University, US Pathogen-microbiota interactions during Clostridium John D. MacMicking, Yale University, US Targeting the unique features of fungal RNA metabolism 16 October 2018 KPѝJPSL infection Cell-autonomous immunity to infection: the art of self- for a new generation of nontoxic drugs Fabian Theis, Helmholtz Zentrum München defense Machine learning in single cell genomics

134 135 7.3 SEMINARS AND COLLOQUIA

03 July 2018 28 May 2019 01 July 2019 02 July 2018 Tom Cooper, Baylor College of Medicine, Houston, US Markus Diefenbacher, University of Würzburg Melanie Brinkmann, Technical University Braun- Andreas Müller, Otto-von-Guericke University in Alternative splicing regulatory networks in development Targeting protein stability in cancer: mouse and organoid schweig Magdeburg and their disruption in disease models 4L[PJ\SV\ZHUKT\S[PMHJL[LK!OV^OLYWLZ]PY\ZLZÄUL[\UL Dissecting Leishmania major proliferation and host cell the innate immune response tropism by novel in vivo biosensors 19 June 2018 Mirjana Kessler, Charité University Medicine Berlin Barbara Treutlein, Max Planck Institute for Evolution- Chronic Chlamydia infection organoid model & origins of 17 June 2019 25 June 2018 ary Anthropology, Leipzig tubal disease Nicola Gagliani, Center for Internal Medicine, UKE )UDQN.LUFKKRσ8QLYHUVLW\+RVSLWDO8OP Reconstructing human organ development using single- Hamburg Relevance beyond HIV: novel antiretroviral restriction cell transcriptomics Kai Kretzschmar, Hubrecht Institute, NL CD4 T cell functional heterogeneity and plasticity: factors 4VKLSSPUNLWPKLYTHSZ[LTJLSSL_WHUZPVUHUKKPќLYLU[PH understanding immune homeostasis and its underlying 22 May 2018 tion in a dish mechanisms 22 June 2018 Lingling Chen, Shanghai Institute of Biochemistry Sammy Bedoui, University of Melbourne, AU and Cell Biology, CN 05 April 2019 27 May 2019 Innate regulation of CD8 T cell immunity The diversity of long non-coding RNAs, their generation and Matthias Lutolf, EPFL, CH Thomas Pietschmann, Institute of Experimental Virol- function Engineering next-generation intestinal organoids ogy, Twincore Hannover 04 June 2018 Genetic determinants of severe respiratory syncytial virus Andrew MacDonald, University of Manchester, UK 08 May 2018 13 March 2019 infection in infants Dendritic cells and macrophages in promotion and Helge Grosshans, Friedrich Miescher Institute for Sina Bartfeld, University of Würzburg YLN\SH[PVUVM[`WLPUÅHTTH[PVU Biomedical Research, Basel, CH Infection, innate immune signaling and cancer in the gut 22 May 2019 Cell fate control through post-transcriptional regulation $GDP *UXQGKRσ +HLQULFK 3HWWH ,QVWLWXWH /HLEQL] 28 May 2018 and oscillatory gene expression Henner Farin, University of Frankfurt Institute for Experimental Virology Hamburg Klaus Osterrieder, FU Berlin Stem cell-derived organoids as genetic models for signal- Repressive chromatin states and herpesvirus latency )PJVKVUKLVW[PTPaH[PVUPUOLYWLZHUKPUÅ\LUaH]PY\ZLZ! 24 April 2018 ing in the colon cancer microenvironment establishment: Who is in the driving seat? H^H`[VUL^TVKPÄLKSP]L]PY\Z]HJJPULZ& Claus-Dieter Kuhn, University of Bayreuth The role of piRNAs in planarian regeneration 13 May 2019 07 May 2018 Elisa Monzon-Casanova, Babraham Institute, University Jan Rohr, University Hospital Freiburg 10 April 2018 VIROLOGY AND IMMUNOBIOLOGY of Cambridge, UK ; JLSS JVVWLYH[P]P[` ZOHWLZ HU[PNLUZWLJPÄJ PTT\UL Henrik Ørum, CiVi Biopharma, US Essential roles for the RNA-binding proteins PTBPs during responses RNA therapeutics - the long road to success SEMINAR S`TWOVJ`[LKL]LSVWTLU[HUKLќLJ[VYM\UJ[PVUZ 23 April 2018 25 November 2019 06 May 2019 Simone Becattini, Sloan Kettering Institute, Memorial Andreas Pichlmair, Technical University München Percy Knolle, Technical University München Sloan Kettering Cancer Center New York, US ORGANOID CLUB Intracellular organization of the innate immune response – Metabolic activation of CD8 T cells in the liver causing Host-microbe symbiosis in the gut: a two-sided story and its disturbance by viruses tissue damage 22 October 2019 09 April 2018 Motaharehsadat Heydarian, University of Würzburg 18 November 2019 28 January 2019 Thomas Tüting, University Hospital for Dermatology and Pargev Hovhannisyan, University of Würzburg Bernhard Nieswandt, RVZ Würzburg Friedemann Weber, JLU Giessen and Venereology Magdeburg Organoids derived from female genital tract as infection 0ZJOHLTPJZ[YVRL!H[OYVTIVPUÅHTTH[VY`KPZLHZL& Induction and suppression of the interferon response by Redirecting antiviral host defense against cancer models segmented negative-sense RNA viruses 11 November 2019 08 February 2019 02 October 2019 Luka Cicin-Sain, HZI Braunschweig 21 January 2019 Elvira Mass, University of Bonn Marco Metzger, University Hospital Würzburg, Fraun- The latency of CMV in balance with the host immune Neva Caliskan, HIRI Würzburg Is neurodegenerative disease a kind of cancer? hofer Institute for Silicate Research ISC, TERM system Translating viral and cellular frameshift genes one codon Intestinal organoids in preclinical research at a time 08 February 2018 28 October 2019 Stephan Becker, Philipps University Marburg Jason Spence, University of Michigan, US Caspar Ohnmacht, Center of Allergy and Environment 14 January 2019 ;YHUZJYPW[PVUHUKYLWSPJH[PVUVMÄSV]PY\ZLZ A cellular atlas of the developing human intestinal stem (ZAUM), TU and Helmholtz Zentrum München Loretta Tuosto, Sapienza University Rom, IT cell niche Regulating the regulators: microbiome, Tregs and den- Human CD28 costimulatory molecule: pro-infammatory 29 January 2018 dritic cells functions beyond a qualitative and quantitative support Stipan Jonjic, University of Rijeka, HR 25 June 2019 to TCR signals Brain-resident memory CD8 T cells induced by congenital Oliver Hartmann, University of Würzburg 18 July 2019 CMV infection prevent brain pathology and virus re- Microscopy of organoids Ralf Bartenschlager, University Hospital Heidelberg 17 December 2018 activation Flaviviridae - host cell interactions: A tale of proteins, lipids Susanne Stutte, LMU München 25 June 2019 and RNA Type-1-interferon suppresses appetite, induces mal- 15 January 2018 Matt Zilbauer, University of Cambridge, UK nutrition and alters immune cell composition by interfering Wolfgang Schamel, Centre for Biological Signalling Human intestinal epithelial organoids - tools to investigate 15 July 2019 with the endocrine system Studies (BIOSS), University of Freiburg LWPNLUL[PJZPUOLHS[OHUK0UÅHTTH[VY`)V^LS+PZLHZLZ Steeve Boulant, University Hospital Heidelberg Mechanisms of abTCR and gdTCR activation: from Importance of type III interferon and cellular polarity on 03 December 2018 signalling to new cancer immunotherapy concepts 18 June 2019 host/enteric pathogen interaction at intestinal epithelium Oliver Kurzai, University of Würzburg Elmar Wolf, University of Würzburg From immune recognition of fungal pathogens towards Identifying MYC-associated oncogenic targets by genetic 08 July 2019 personalized medicine screens in complex systems Peter Murray, Max Planck Institute of Biochemistry Martinsried Myeloid metabolism and immune control

136 137 7.3 SEMINARS AND COLLOQUIA

OTHER SEMINARS 31 January 2018 Stefan Raunser, Max Planck Institute of Molecular Only selected seminars of ZINF members or related to Physiology, Dortmund infectious diseases are listed. The power of cryo-EM to elucidate biological mechanisms

INAUGURAL LECTURES PHYSICO MEDICA

03 May 2019 11 December 2019 Cynthia Sharma, Institute of Molecular Infection Bio- Chase Beisel, Helmholtz-Institute for RNA-based logy (IMIB), Würzburg Infection Research (HIRI), Würzburg and Jörg Vogel, Kleine RNAs in pathogenen Bakterien – mehr als nur vier Institute of Molecular Infection Biology (IMIB) in Buchstaben Würzburg Human Nature - Die CRISPR Revolution Oliver Kurzai, Institute for Hygiene and Microbiology Film mit anschließender Diskussion (IHM), Würzburg Das vergessene Königreich – wie Pilze unser Leben 11 December 2018 verändern Thomas Cooper, Baylor College of Medicine, Houston, Texas, US 02 June 2018 Investigation of myotonic dystrophy revealed a network Wolfgang Kastenmüller, Institute of Systems Immuno- of developmentally regulated alternative splicing, the logy, Würzburg disruption of which causes disease features Das Immunsystem in Raum und Zeit 03 July 2018 Georg Gasteiger, Institute of Systems Immunology, Thomas Cooper, Baylor College of Medicine, Houston, Würzburg Texas, US Netzwerke geweberesidenter Immunzellen Alternative splicing regulatory networks in development and their disruption in disease

BIOZENTRUMS-KOLLOQUIUM

27 November 2019 Christof Niehrs, Institute of Molecular Biology, Mainz Decoding of regulatory R-loops

13 November 2019 Antonio Di Pietro, Department of Genetics, University of Córdoba, ES Dynamics of host adaptation in the fungal pathogen Fusarium oxysporum

08 May 2019 Bernd Bukau, Center of Molecular Biology (ZMBH), University of Heidelberg Folding and assembly of newly synthesized proteins YL]LHSLKI`YPIVZVTLWYVÄSPUN

14 November 2018 Dean W. Felsher, Standford School of Medicine, Stan- ford University, US MYC oncogene is a master regulator of the immune response

24 October 2018 Georg Gasteiger, Institute of Systems Immunology, Würzburg Local players in immunity: networks of tissue resident lymphocytes

06 June 2018 Anne Willis, MRC Unit at the University of Cambridge, UK Regulation of mRNA translation via control of elongation in health and disease states

138 139 7.4 FUNDING

BROCHADO, ANA RITA DFG (DO 1275/6-1): Functional analysis of downstream 7.4 FUNDING open chromatin induced in HSV-1 infection DFG Emmy Noether Grant: Deciphering molecular mechanisms of bacterial cell death and persistence using DFG (DO 1275/10-1): Integrative analyses of CMV FUNDING IN 2018-2019 antibiotic combinations translatomes and MHC-I peptidomes

StMWi HIRI Seed Grants #9: Intrinsic host-cell defenses limiting cytomegalovirus transcription and translation in CALISKAN, NEVA latency; #10: Establishment of Grad-seq to study RNA- BARTFELD, SINA BEISEL, CHASE protein interaction networks in human cells using the RNA Society: RNA Salon-Würzburg /:= OVZ[ ZO\[Vќ TVKLS" ! /L[LYVNLULP[` VM [OL EU Horizon 2020: REMODEL – Research models in DFG SPP 2141: Much more than defence – the multiple host response to acute and chronic infection in primary infection, cancer, and tissue regeneration: replacement functions and facets of CRISPR-Cas (BE 6703/1-1): myeloid cells and translation. Twinning Project with IBMC (Portugal), Functional characterization of extensively self-targeting University of Utrecht (NL), University of Copenhagen (DK) CRISPR-Cas systems in the bacterial plant pathogen DANDEKAR, THOMAS Xanthomonas albilineans DFG GRK 2157: 3D Infect – 3D Tissue Models for DFG SFB/TRR 34: Pathophysiology of Staphylococci in EINSELE, HERMANN Studying Microbial Infections by Human Pathogens ERA-Net JPI-EC-AMR (01KI182): CRISPRattack – the Post-Genome-Era (Project A08): A systems biology (Project 10): Analysis of the innate immune response of Advancing CRISPR antimicrobials to combat the bacterial perspective of metabolic and regulatory adaptation of European Commission FP7: T-Control – Donor T Cells for gastrointestinal epithelium in 3D organoids pathogen Klebsiella pneumoniae Staphylococcus aureus to infection-related conditions Immune Control (Health-F4-2013-601722): Clinical trial for the treatment of infections and tumor relapse after Käthe und Josef Klinz-Stiftung: Systemic Analysis of Benson Hill (Sponsored Research Agreement): Characteri- DFG SFB/TRR 34: Pathophysiology of Staphylococci in allogeneic HSCT; Clinical trial for the treatment of acute immunological barrier function in organoids from adult zing and enhancing the properties of the Cms1 nuclease the Post-Genome-Era (Project Z01): An integrated view steroid refractory GVHD after allogeneic HSCT stem cells of adaptation of Staphylococcus aureus DARPA (Safe genes program HR0011-17-2-0042): EU Horizon 2020: EURE-CART – European Endeavour Technologies to control, surveil, and counter genome- DFG SFB/TRR 124: FungiNet – Pathogenic fungi and for Chimeric Antigen Receptor Therapies editing nucleases and gene drives their human host: Networks of interaction (Project B01): BEILHACK, ANDREAS Modelling interactions between the host and fungal EU Horizon 2020: CARAMBA – SLAMF7-CAR T cells pathogens by combining metabolic pathway analysis and prepared by Sleeping Beauty gene-transfer for immuno- DFG SFB/TRR 124: FungiNet – Pathogenic fungi and evolutionary game theory therapy of multiple myeloma: a rare hematologic disease their human host: Networks of interaction (Project A03): In BEYERSDORF, NIKLAS vivo analysis of temporal and spatial disease progression DFG SFB/TRR 124: FungiNet – Pathogenic fungi and DFG SFB/TRR 124: FungiNet – Pathogenic fungi and and immune cell recruitment during invasive Aspergillus DFG SFB/TRR 124: FungiNet – Pathogenic fungi and their human host: Networks of interaction (Project B02): their human host: Networks of interaction (Project A02): fumigatus infection their human host: Networks of interaction (Project C06): Interaction networks of signaling molecules and pathways Interaction of Aspergillus fumigatus with human natural Role of secreted Candida albicans proteins in immune between the pathogenic fungi Aspergillus fumigatus and killer cells, dendritic cells DFG SFB/TRR 225: Biofab – From the fundamentals of evasion and Pathogenicity Candida albicans and their human host biofabrication towards functional tissue models (Project DFG SFB/TRR 221: Modulation of graft-versus-host and B08): Time-resolved biophotonics approach cellular DFG FOR 2123: SphingoFOR – Sphingolipid dynamics in DFG GRK 2157: 3D Infect – 3D Tissue Models for graft-versus leukemia immune responses after allogeneic signaling, cell-matrix interactions and matrix remodeling infection control (BE 4080/3-2): Role of sphingolipids in Studying Microbial Infections by Human Pathogens stem cell transplantation (Project A03): CAR-engineered mechanisms in biofabricated constructs the regulation of anti-viral T cell responses (Project 02): Host factors required for the initiation and ;JLSSZ[OH[H\NTLU[[OLNYHM[]LYZ\ZSL\RLTPHLќLJ[VM propagation of Chlamydia trachomatis infections allogeneic HSCT DFG GRK 2157: 3D Infect – 3D Tissue Models for Studying DFG (BE 4080/2-1): The role of CD28-mediated signals in Microbial Infections by Human Pathogens (Project 01): programming and reprogramming of mouse and human IZKF (A-401): NAFLD – The role of the intestinal mycobiome DFG FOR 2830: Advanced Concepts in Cellular Immune Host-pathogen interactions revealed by 3D high resolution memory and induced regulatory T cells in the pathogenesis of the non-alcoholic fatty liver disease Control of Cytomegalovirus (Project 09): Personalized microscopy TLKPJPUL ¶ 9PZR Z[YH[PÄJH[PVU HUK WYL]LU[PVU VM /*4= BMBF (031L0156C): In-vitro test methods to evaluate the StMWi HIRI Seed Grant #12: Functional host-pathogen related disease in transplant patients based on MHC-I- IZKF (B-369): Pharmacological destabilization of tumor LѝJHJ`VMPTT\UVSVNPJHS[OLYHWPLZMVYTHSPNUHU[TLSHUVTH transcriptomics of human macrophages and dendritic ligandomes ,*4[VPUJYLHZL[OLLќLJ[P]LULZZVMPTT\UV[OLYHWL\[PJZ cells challenged with Aspergillus fumigatus and cyto- IZKF (E-298): Therapeutic modulation of regulatory T cells megalovirus BMBF InfectControl 2020: Art4FUN – Antigen-reactive Deutsche José Carreras Leukämie-Stiftung (DJCLS in minipigs to improve wound healing and survival after T cells for the diagnosis and therapy of fungal-associated 9! :LWHYH[PVU VM .]/+ MYVT .]3LќLJ[Z I` myocardial infarction diseases in high-risk patients targeting the TWEAK/Fn14-system DÖLKEN, LARS BMBF Verbundantrag: IMMUNOQUANT – Antibody- and Else-Kröner-Forschungskolleg for Interdisciplinary T cell-based immunotherapy depending on antigen den- Translational Immunology (Coordinator), Else-Kröner- BREHM, KLAUS ,9**VUZVSPKH[VY(^HYK!/LYWLZ]PY\Z,ќLJ[VYZVM95( sity and detection of tumor-associated antigens on solid Fresenius-Stiftung (second funding period) Synthesis, Processing Export and Stability tumors with dSTORM ERANet-LAC (ELAC2015/T080544): NDTND – Develop- m4 (^HYK VM [OL )H]HYPHU 4PUPZ[Y` VM ,JVUVTPJ (ќHPYZ ment of New Diagnostic and Treatment Options for Infect-ERA (ERA-Net), 2nd Call Consortium: eDEVILLI – Wilhelm-Sander-Stiftung (2020.017.1): Development and Media, Energy and Technology Helminthic Neglected Diseases Early Determinants of DNA-Virus Lytic or Latent Infection and evaluation of human natural killer cells with synthetic HU[PNLUZWLJPÄJ YLJLW[VYZ *(9 52 HUK [OLYHWL\[PJ Bayerische Forschungsstiftung (WP2TP3): FortiTher – Wellcome Trust Strategic Award (107475/Z/15/Z): FUGI – DFG FOR 2830: Advanced Concepts in Cellular Immune antibodies for the add-on treatment of invasive fungal Tumor diagnostics for individualized therapy Flatworm Functional Genomics Initiative: Development of Control of Cytomegalovirus (Speaker) (Project 01): infections cestode functional genomics tools Integrative analyses of CMV translatomes and MHC-I ligandomes StMWi HIRI Seed Grant #23: Genetic engineering of Bayerische Forschungsstiftung (AZ-1341-18): KITE – chimeric antigen receptor (CAR) T cells for immunotherapy Kinase inhibitors as therapeutic agents for echinococcosis in cancer and infection

140 141 7.4 FUNDING

ENGSTLER, MARKUS RKI Grant (1369-378): Consiliary Laboratory for HOLZGRABE, ULRIKE KURZAI, OLIVER Echinococcosis DFG GRK 2157: 3D Infect – 3D Tissue Models for Study- )4)- P407 5H[\YZ[VќTLKPaPU! +L]LSVWTLU[ VM UVU EU Horizon 2020: HDM-FUM – Host-Directed Medicine in ing Microbial Infections by Human Pathogens (Project 09): immunosuppressive FK506 analogues as macrophage Invasive Fungal Infections +L]LSVWTLU[ VM [ZL[ZL Å`[YHUZTP[[LK (MYPJHU [Y`WHUV GASTEIGER, GEORG infectivity potentiator (MIP) inhibitors for the treatment of somes in human skin tissue models Legionella pneumophila, Burkholderia pseudomallei, and DFG SFB/TRR 124: FungiNet – Pathogenic fungi and ERC Starting Grant: Tissue-resident Lymphocytes – ;Y`WHUVZVTHJY\aPinfections (16GW0212): Development their human host: Networks of interaction (Project C03): DFG SPP 1726: Microswimmers – From Single Particle +L]LSVWTLU[HUK-\UJ[PVUPU¸YLHSSPML¹*VU[L_[Z of MIP inhibitors of the FK506 type for the treatment of Intrinsic modulation of neutrophil antifungal activity Motion to Collective Behaviour (EN 305/4-3 and EN ;Y`WHUVZVTHJY\aPinfections against Candida albicans 305/8-1): From solitary swimmers to swarms and back: DFG Emmy Noether Grant: Adaptive-innate lymphocyte [Y`WHUVZVTLZVU[OLPYQV\YUL`[OYV\NO[OL[ZL[ZLÅ` crosstalk – mechanisms, functions, and consequences DMTC (Project 10.44): Pharmaceutical Development of BMBF InfectControl 2020: FINAR & FINAR 2.0 – Fungal Antivirulence Compounds Against BW Pathogens Infections and Azole Resistance DFG German-African Cooperation Projects in Infectiology DFG SPP 1937: Innate lymphoid cells (GA 2129/2-1): (EN 305/5-1 and EN 305/7-1): Antibody clearance as Tissue-niches and cellular interactions of mouse and Bayerische Forschungsstiftung (AZ 1204-16): Antibiotic- BMBF InfectControl 2020: RAI students – Rational use of virulence factor in African sleeping sickness human ILCs at single-cell resolution osmoprotective ionic liquids antibiotics through information and communication: New target group - students of human medicine and pharmacy .LYTHU0ZYHLSP -V\UKH[PVU MVY :JPLU[PÄJ 9LZLHYJO HUK Elitenetzwerk Bayern, Internationales Doktorandenkolleg: +L]LSVWTLU[.0-0 !,ќLJ[VML_[YH Receptor dynamics – Emerging Paradigm for Novel Drugs BMBF InfectControl 2020: Transsectoral Research cellular Trypanosoma brucei vesicles on collective and GEIBEL, SEBASTIAN 7YVQLJ[! +L]LSVWTLU[ VM WH[O^H`ZWLJPÄJ K\HSZ[LYPJ 7SH[MVYT ;-7 ¶ .LUVTL^PKL PKLU[PÄJH[PVU VM YPZR ZVJPHSWHYHZP[LTV[PSP[`HUKKL]LSVWTLU[PU[OL[ZL[ZLÅ` ligands and investigation into their mode of action markers in the immune response against infections Elitenetzwerk Bayern (N-BM-2013-246): Structural biology of mycobacterial secretion machines Bayern Innovativ (PBN-MED-1604-0009): Personalisierte BMBF InfectControl 2020: Innovationslabor Imaging Medizin für Menschen mit psychischen Erkrankungen ERHARD, FLORIAN BMBF Center for Sepsis Control and Care CSCC: Leibniz-Gemeinschaft: PHARMSAFE – Development of a 8<(5;04¶8\HU[PÄJH[PVUVM0UUH[L0TT\UL-\UJ[PVUPU DFG FOR 2830: Advanced Concepts in Cellular Immune GOMEZ DE AGÜERO, MERCEDES predictive solid state tool for improved pharmaceutical safety Whole Blood Infection Assays Control of Cytomegalovirus (Project 01): Integrative analyses of CMV translatomes and MHC-I ligandomes Novartis Foundation for medical-biological Research IZKF (A-401): NAFLD – The role of the intestinal mycobiome in the pathogenesis of the non-alcoholic fatty StMWi HIRI Seed Grants #10: Establishment of GRAD- Ambizione Swiss National Funding KASTENMÜLLER, WOLFGANG liver disease seq to study RNA-protein interaction networks in O\THUJLSSZ\ZPUN[OL/:=OVZ[ZO\[VќTVKLS" ! ERC Consolidator Grant: Spatiotemporal regulation of BMG/RKI grant (1369-240): NRZMyk – Nationales Heterogeneity of the host response to acute and chronic T-cell Priming Referenzzentrum für Invasive Pilzinfektionen infection in primary myeloid cells GROSS, ROY Else-Kröner-Fresenius-Stiftung: Else-Kröner-Fresenius- DFG GRK 2157: 3D Infect – 3D Tissue Models for Center for Advanced Medical & Humanitarian Studies Studying Microbial Infections by Human Pathogens KISKER, CAROLINE Würzburg - Mwanza FRAUNHOLZ, MARTIN (Project 06): Characterization of host cell responses after Bordetella pertussis infection using 2D and 3D in vitro DFG GSC 106: GSLS – Excellence Initiative by the DFG SFB/TRR 34: Pathophysiology of Staphylococci airway test systems German federal and state governments in the Post-Genome-Era (Project C11): Host cell death LÖFFLER, JÜRGEN induced by Staphylococcus aureus and its linkage to DFG GRK 2243: UBI – Understanding Ubiquitylation: phagosomal escape From Molecular Mechanisms to Disease (Project B01): DFG SFB/TRR 124: FungiNet – Pathogenic fungi and HERRMANN, THOMAS Structural and functional analysis of the Fbw7-Usp28 their human host: Networks of interaction (Project A02): DFG FOR 2123: SphingoFOR – Sphingolipid dynamics complex; (Project B03): Mechanism of substrate Interaction of Aspergillus fumigatus with human natural in infection control (FR 1504/4-1): Role of the acid DFG FOR 2799: Receiving and Translating Signals via the recognition by chlamydial DUBs killer cells and dendritic cells sphingomyelinase/ceramide system in lung edema gamma-delta T Cell Receptor (HE 2346/8-1): Phylogeny induced by Staphylococcus aureus toxin HUK-\UJ[PVUVM=ф =х;JLSSZ¶/\THU]Z*HTLSPKZ BMBF InfectControl 2020: Art4FUN – Antigen-reactive T cells for the diagnosis and therapy of fungal-associated StMWi HIRI Seed Grant #7: Mode of action of the novel +-./,!=ф =х;JLSSZ¶0KLU[PÄJH[PVUPUUVU KLINKER, HARTWIG diseases in high-risk patients virulence regulatory RNA SSR42 during Staphylococcus primate species and analysis of molecular determinants aureus-induced osteomyelitis of antigen-recognition NIH and BMBF (01 KG 0915): START – Strategic Timing BMBF (BayBIO 1606-0003 - TbaseIA): T cell-based of Antiretroviral Treatment monitoring for invasive Aspergillus in patients with Wilhelm Sander-Stiftung (2013.907.2): Mechanistic basis haematological diseases MVYUL^Z[YH[LNPLZVMфх;JLSSTLKPH[LKPTT\UV[OLYHWPLZ Hector-Stiftung (STIF-99): Individualized cancer therapy FROSCH, MATTHIAS against multiple myeloma with kinase inhibitors using drug monitoring – optimization Wilhelm Sander-Stiftung (2015.083.1): Diagnostic by minimally invasive at-home sampling strategies for cancer patients with respiratory fungal EU/ECDC grant: Coordination of activities for laboratory Deutsche Krebshilfe (70112079): Function and infections surveillance of invasive bacterial diseases (N. meningitidis, therapeutic relevance of chromosome 6 localized genes /PUÅ\LUaHLHUK:WUL\TVUPHL) in Member States and for recognition and elimination of tumor cells by human StMWi HIRI Seed Grant #12: Functional host-pathogen EEA/EFTA countries =ф =х;JLSSZ KOZJAK-PAVLOVIC, VERA transcriptomics of human macrophages and dendritic cells challenged with Aspergillus fumigatus and cyto- RKI Grant (1369-237): National Reference Laboratory for DFG GRK 2157: 3D Infect – 3D Tissue Models for megalovirus Meningococci and /HLTVWOPS\ZPUÅ\LUaHL Studying Microbial Infections by Human Pathogens (Project 03): Bacterial and host cell factors important for the invasion and dissemination of Neisseria gonorrhoeae

142 143 7.4 FUNDING

LUTZ, MANFRED DFG (MO 846/6-2): Phenotypic switching and genomic DFG GRK 2243: UBI – Understanding Ubiquitylation: SCHUBERT-UNKMEIR, ALEXANDRA alterations as host adaptation mechanisms of the From Molecular Mechanisms to Disease (Project B03): DFG (LU 851/6-2): VLA-1-dependent migration patterns opportunistic fungal pathogen Candida albicans Mechanism of substrate recognition by chlamydial DUBs DFG GRK 2157: 3D Infect – 3D Tissue Models for Studying and functions of monocytic myeloid-derived suppressor Microbial Infections by Human Pathogens (Project 04): cells (M-MSDC) during autoimmunity and infection DFG (MO 846/7-2): Systematic functional analysis of the DFG FOR 2123: SphingoFOR – Sphingolipid dynamics Meningococcal ligands and molecular targets required for zinc cluster transcription factor family of the pathogenic in infection control (RU 631/31-1): Sphingolipids in HKOLZPVUHUKWLUL[YH[PVUVM[OLISVVKJLYLIYVZWPUHSÅ\PK DFG (LU 851/14-1): Conversion of anergic non-regulatory yeast Candida albicansI`HY[PÄJPHSHJ[P]H[PVU gonococcal infection barrier under shear stress into Foxp3-IL-10+ regulatory T cells by dendritic cells in vivo NIH/NIAID: Novel Azole Resistance Mechanisms in DFG (RU 631/12-1): Regulation of Expression of opa DFG FOR 2123: SphingoFOR – Sphingolipid dynamics IZKF (A-303): Role of the immune system in the Candida albicans Genes of Neisseria gonorrhoeae by Antisense RNA in infection control (SCHU 2394/2-2): Analysis of the pathogenesis of Parkinson‘s Disease functional relevance of sphingomyelinases and ceramide in meningococcal pathogenesis Wilhelm Sander-Stiftung (2013.60.1): Functional roles of direct and bystander release of IL-12 by dendritic cells for MUNSCHAUER, MATHIAS SALIBA, ANTOINE-EMMANUEL BaCaTec (Bavaria California Technology Center): Blood T cell activation and anti-tumor immunity brain barrier failure during bacterial and viral infections Helmholtz Association (HGF) Young Investigator Program DFG GE 539/14-1: Understanding the cellular inventory StMWi HIRI Seed Grant #22: Heterogeneity of the host of pediatric kidney tumors response to acute and chronic infection in primary myeloid cells SIDACTION grant: A triple approach to study HIV-1, the SEIBEL, JÜRGEN OHLSEN, KNUT infected host cells and opportunistic bacteria DFG SFB/TRR 225: Biofab – From the fundamentals of DFG SFB/TRR 34: Pathophysiology of Staphylococci in :[4>P /090 :LLK .YHU[Z ! :PUNSL JLSS WYVÄSPUN VM biofabrication towards functional tissue models (Project METZGER, MARCO the Post-Genome-Era (Project A02): Phosphoproteomic [OL PTT\UL YLZWVUZL [V PUÅ\LUaH ]HJJPUH[PVU! WYVVM B05): Glycoengineering as a tool to control the behavior analysis of Staphylococcus aureus: Functional charac- of concept; #17: Impact of microbial colonization on of mesenchymal stem cells in biofabrication processes EU-IMI (807015): IM2PACT – Investigating Mechanisms [LYPaH[PVUVMRPUHZLZHUKPKLU[PÄJH[PVUVM[OLPYZ\IZ[YH[LZ" stromal cells from gut-draining lymph nodes; #18: Cellular and Models Predictive of Accessibility of Therapeutics (Project Z03): In vivo imaging of Staphylococcus aureus collaboration transfers competence for viral defense and DFG FOR 2123: SphingoFOR – Sphingolipid dynamics into the brain infections quenches single-cell heterogeneity; #22: Heterogeneity in infection control (SE 1410/6-2): Central project, of the host response to acute and chronic infection in Sphingolipid metabolic pathways in infection control by the DFG GRK 2157: 3D Infect – 3D Tissue Models for BMBF Health Research (GFTARV62): PyrBac – Target primary myeloid cells \ZLVMJOLTPJHSS`Z`U[OLZPaLKTVKPÄLKZWOPUNVSPWPKZHUK Studying Microbial Infections by Human Pathogens validation for pharmaceutical drug development: Valida- in the era of sphingolipidomics; (SE 1410/7-1): Coating of (Project 08): Establishing a human intestinal tissue model tion of pyruvate kinase as novel metabolic target to endotracheal tubes with sphingosine to prevent bacterial to study host and pathogen determinants that restrict combat antibiotic resistant bacteria growth and ventilator-associated pneumonia Salmonella enterica infection SCHNEIDER-SCHAULIES, JÜRGEN BMBF (01DN16034): Synthesis of tailored modular hybrid BMBF (031B0073B): KMUinnovativ – Establishment DFG FOR 2123: SphingoFOR – Sphingolipid dynamics in oligosaccharides of human intestinal tissue models for preclinical high- PÉREZ, CHRISTIAN infection control (SCHN 320/24-2): Role of sphingolipids throughput screening in the regulation of anti-viral T cell responses DFG SFB/TRR 124: FungiNet – Pathogenic fungi and BMBF-individualisierte Stammzelltherapien (01EK1608A): their human host: Networks of interaction (Project C01): SHARMA, CYNTHIA HiPSTAR – Establishment, validation, and standardization Molecular characterization of Candida albicans mucosal of individualized hiPS-based blood brain barrier models colonization, infection, and translocation SCHNEIDER-SCHAULIES, SIBYLLE DFG GRK 2157: 3D Infect – 3D Tissue Models for for Alzheimer‘s drug development and testing in vitro Studying Microbial Infections by Human Pathogens DFG SPP 1656: Intestinal Microbiota (PE 2371/3-1): DFG GRK 2157: 3D Infect – 3D Tissue Models for Studying (Project 05): Virulence factors and regulators required AiF-ZIM (ZF4353102NK7): Development of a novel Genetic circuits underlying fungal-bacterial interactions in Microbial Infections by Human Pathogens (Project 07): during Campylobacter jejuni infections combination compound for the treatment of a decubitus the mammalian intestine Membrane and protein microdomains governing measles wound and development of a decubitus skin model virus transmission at entry and exit interface DFG SPP 1784: Chemical Biology of native Nucleic DFG (PE 2371/2-1): Mechanisms of host colonization by (JPK 4VKPÄJH[PVUZ :/  ! 0KLU[PÄJH[PVU HUK Bayerische Forschungsstiftung: FORTiTher – Research a eukaryotic member of the microbiota DFG FOR 2123: SphingoFOR – Sphingolipid dynamics characterization of pseudouridine in mRNAs and association for tumor diagnostics for individualized therapy in infection control (SCHN 405/10-2): Sphingomyelinase non-coding RNAs of the bacterial human pathogen activation in T cells: Implications for T cell activation and Campylobacter jejuni StMWi: RoboMuk – Robotics-based production of per- paralysis; (SCHN 405/11-2): Central project sonalized organoid test systems for in vitro testing of RUDEL, THOMAS DFG SPP 2002: Small Proteins in Prokaryotes, an *-;9T\[H[PVUZWLJPÄJJ`Z[PJÄIYVZPZHNLU[Z Unexplored World (SH 580/7-1): Central Project Z02, ERC Advanced Grant: Neutrophil – Chlamydia Interactions 9PIVZVTL 7YVÄSPUN HUK )PVPUMVYTH[PJZ" :/   ! StMWi HIRI Seed Grant #2: miR-mediated regulation at the Crossroad of Adaptation and Defence SCHOEN, CHRISTOPH Exploring micro-proteins in the food-borne pathogen of mucus producing intestinal cells during infection and Campylobacter jejuni PUÅHTTH[PVU DFG SFB/TRR 34: Pathophysiology of Staphylococci in DFG SPP 2141: Much more than defence – the multiple the Post-Genome-Era (Project C11): Staphylococcus functions and facets of CRISPR-Cas (SCHO 1322/3-1): DFG SPP 2141: Much more than defence – the multiple aureus induced host cell death mechanisms The CRISPR/Cas system in Neisseria meningitidis and its functions and facets of CRISPR-Cas (SH 580/9-1): potential role in host cell adhesion Mechanisms and functions of endogenous RNA-targeting MORSCHHÄUSER, JOACHIM DFG GRK 2157: 3D Infect – 3D Tissue Models for by CRISPR-Cas9 in Campylobacter jejuni Studying Microbial Infections by Human Pathogens StMWi HIRI Seed Grant #8: The role of the RNA chaperone DFG SFB/TRR 124: FungiNet – Pathogenic fungi and (Project 02): Host factors required for the initiation and ProQ in riboregulation of meningococcal virulence Infect-ERA (ERA-NET) 2nd Call Junior Consortium: their human host: Networks of interaction (Project C02): propagation of Chlamydia trachomatis infections; (Project CampyRNA - Combining high-throughput and single-cell Regulation of Candida albicans virulence traits by protein 03): Bacterial and host cell factors important for the analyses to study RNA regulators important for the early kinases invasion and dissemination of Neisseria gonorrhoeae steps of Campylobacter infection

144 145 7.4 FUNDING

StMWi HIRI Seed Grants #6: Exploring RNA-Protein- DFG (VO 875/18-1): Gottfried Wilhelm Leibniz Preis DFG SPP 1617: Phenotypic Heterogeneity and Complexes in the gastric pathogen Helicobacter pylori Sociobiology of Bacterial Populations (ZI 665/2-1): using Grad-Seq; #24: Elucidation of the function of Infect-ERA (ERA-NET) 2nd Call Consortium: The Nice Bug Heterogeneous gene expression, metabolic variability the tRNA modifying enzyme GidA as a potential global - Commensalism versus disease? Asymptomatic carriage HUKKPќLYLU[PH[PVUPUStaphylococcus epidermidisIPVÄSTZ translational regulator in Pseudomonas aeruginosa or urosepsis DFG German-African Cooperation Projects in StMWi HIRI Seed Grants #1: Discovery of RNA regulators Infectiology: ShARE – Staphylococci in Africa: Resistance of the enteric pathogen *SVZ[YPKP\TKPѝJPSL; #3: Dynamic & Epidemiology (ZI 665/3-1): Molecular epidemiology and SMYTH, REDMOND reprogramming of the transcriptional landscape of antimicrobial resistance mechanisms in staphylococci Salmonella enterica during gastrointestinal infection; from various geographic regions in Africa BMBF: Computational methods to decipher function- #4: The role of RNA in antibiotic resistance and mode associated structure in long ncRNAs of action; #5: Dual RNA-seq to decipher the impact of BMBF #1Health-PREVENT: One Health Interventions WYLL_PZ[PUNPUÅ\LUaH(]PY\ZPUMLJ[PVUVU[OL[YHUZJYPW[PVUHS to Prevent Zoonotic Spread of Antimicrobial Multidrug- WYVÄSL HUK ]PY\SLUJL VM Streptococcus pneumoniae; Resistant Bacterial Microorganisms (01KI1727E): #7: Mode of action of the novel virulence regulatory Reducing the AMR burden in farm environments: Impact STICH, AUGUST RNA SSR42 during Staphylococcus aureus-induced on human commensals and zoonotic pathogens osteomyelitis; #8: The role of the RNA chaperone ProQ in Rexroth Foundation: Interdisciplinary Center for Research riboregulation of meningococcal virulence; #12: Functional in Tropical Medicine host-pathogen transcriptomics of human macrophages and dendritic cells challenged with Aspergillus fumigatus German Academic Exchange Service: Development of a HUK J`[VTLNHSV]PY\Z" ! :PUNSL JLSS WYVÄSPUN VM [OL triangular partnership Bugando - Stellenbosch - Würzburg PTT\UL YLZWVUZL [V PUÅ\LUaH ]HJJPUH[PVU! WYVVM VM in medical education and research concept; #21: Modulation of microbiota by oral delivery of anti-sense oligonucleotides Else-Kröner-Fresenius-Stiftung: Control of Chagas and other parasitic diseases in Colombia VOGEL, ULRICH

VOGEL, JÖRG IBD-labnet Coordination of Activities for Laboratory Surveillance of Invasive Bacterial Diseases: European DFG SFB/TRR 34: Pathophysiology of Staphylococci Centre for Disease Control and Prevention, contract 4 in the Post-Genome-Era (Project C06): Post-invasion ECD.9696 under framework contract ECDC 2016/001 events in Staphylococcus aureus infected host cells – A combined transcriptomics/proteomics in vivo approach RKI grant (1369-237): National Reference Laboratory for Meningococci and /HLTVWOPS\ZPUÅ\LUaHL DFG GRK 2157: 3D Infect – 3D Tissue Models for Studying Microbial Infections by Human Pathogens (Project 08): Establishing a human intestinal tissue model to study host and pathogen determinants that restrict WESTERMANN, ALEXANDER Salmonella enterica infection SIDACTION Grant: A triple approach to study HIV-1, the DFG FOR 1680: Unravelling the Prokaryotic Immune infected host cells and opportunistic bacteria System (VO 875/7-2): Alternative functions of the CRISPR-associated endonuclease Cas9 StMWi HIRI Seed Grants #3: Dynamic reprogramming of the transcriptional landscape of Salmonella enterica DFG SPP 1784: Chemical Biology of native Nucleic Acid during gastrointestinal infection; #5: Dual RNA-seq to 4VKPÄJH[PVUZ =6 ! +PZJV]LY` HUK JOHYHJ[LYP KLJPWOLY [OL PTWHJ[ VM WYLL_PZ[PUN PUÅ\LUaH ( ]PY\Z aH[PVUVM95(TVKPÄJH[PVUZPUHIHJ[LYPHSTVKLSWH[OVNLU PUMLJ[PVU VU [OL [YHUZJYPW[PVUHS WYVÄSL HUK ]PY\SLUJL of Streptococcus pneumoniae; #12: Functional host- DFG SPP 1935: Deciphering the mRNP code – RNA- pathogen transcriptomics of human macrophages and bound determinants of post-transcriptional gene dendritic cells challenged with Aspergillus fumigatus and regulation (VO 875/17-2): Characterization of factors and cytomegalovirus mechanisms of starvation-induced control of TOP mRNA translation

DFG SPP 2002: Small Proteins in Prokaryotes, an ZIEBUHR, WILMA Unexplored World (VO 875/20-1): Functions of μ-proteins regulated during Salmonella infection DFG SFB/TRR 34: Pathophysiology of Staphylococci in the Post-Genome-Era (Project B4): Regulation of DFG (VO 875/14-1): Exploring biogenesis and functions methionine metabolism in staphylococci: Impact on of 3‘UTR-derived small regulatory RNAs Ä[ULZZHUK]PY\SLUJL

DFG (VO 875/19-1): Understanding PinT, a noncoding RNA timer of virulence gene expression

146 147 7.5 PUBLICATIONS

Rudelius M, Rosenfeldt MT, Leich E, Rauert-Wunderlich BEISEL, CHASE 7.5 PUBLICATIONS H, Solimando AG, Beilhack A, Ott G, Rosenwald A (2018) Inhibition of focal adhesion kinase overcomes resistance Agrawal DK, Tang X, Westbrook A, Marshall R, of mantle cell lymphoma to ibrutinib in the bone marrow Maxwell CS, Lucks J, Noireaux V, Beisel CL, Dunlop PUBLICATIONS IN 2018-2019 (listed in alphabetical order) microenvironment. Haematologica 103(1):116-125 MJ, Franco E (2018) Mathematical Modeling of RNA- Based Architectures for Closed Loop Control of Gene Please note that only publications of ZINF members that are relevant for infectious disease research are listed below. Solimando AG, Brandl A, Mattenheimer K, Graf C, Ritz Expression. ACS Synthetic Biology 7(5):1219-1228 M, Ruckdeschel A, Stühmer T, Mokhtari Z, Rudelius M, Dotterweich J, Bittrich M, Desantis V, Ebert R, Trerotoli P, Alper HS, Beisel CL (2018) Advances in CRISPR Frassanito MA, Rosenwald A, Vacca A, Einsele H, Jakob Technologies for Microbial Strain Engineering. F, Beilhack A (2018) JAM-A as a prognostic factor and Biotechnology Journal 13(9):e1800460 BARQUIST, LARS BARTFELD, SINA new therapeutic target in multiple myeloma. Leukemia 32(3):736-743 Beisel CL (2018) CRISPR tool puts RNA on the record. Cain AK, Boinett CJ, Barquist L, Dordel J, Fookes M, Renz H, Adkins BD, Bartfeld S, Blumberg RS, Farber DL, Nature 562(7727):347-349 Mayho M, Ellington MJ, Goulding D, Pickard D, Wick RR, Garssen J, Ghazal P, Hackam DJ, Marsland BJ, McCoy Ullrich E, Abendroth B, Rothamer J, Huber C, Büttner- Holt KE, Parkhill J, Thomson NR (2018) Morphological, KD, Penders J, Prinz I, Verhasselt V, von Mutius E, Weiser Herold M, Buchele V, Vogler T, Longerich T, Zundler S, Bober JR, Beisel CL, Nair NU (2018) Synthetic Biology genomic and transcriptomic responses of Klebsiella JN, Wesemann DR, Hornef MW (2018) The neonatal Völkl S, Beilhack A, Rose-John S, Wirtz S, Weber GF, Approaches to Engineer Probiotics and Members of the pneumoniae to the last-line antibiotic colistin. :JPLU[PÄJ window of opportunity-early priming for life. Journal of Ghimire S, Kreutz M, Holler E, Mackensen A, Neurath MF, Human Microbiota for Biomedical Applications. Annual Reports 8(1):9868 Allergy and Clinical Immunology 141(4):1212-1214 Hildner K (2018) BATF-dependent IL-7RhiGM-CSF+ T Review of Biomedical Engineering 20:277-300 cells control intestinal graft-versus-host disease. Journal Holmqvist E, Li L, Bischler T, Barquist L, Vogel J (2018) Yan HHN, Siu HC, Law S, Ho SL, Yue SSK, Tsui WY, of Clinical Investigation 128(3):916-930 Dugar G, Leenay RT, Eisenbart SK, Bischler T, Aul BU, Global Maps of ProQ Binding In Vivo Reveal Target Chan D, Chan AS, Ma S, Lam KO, Bartfeld S, Man Beisel CL, Sharma CM (2018) CRISPR RNA-Dependent Recognition via RNA Structure and Stability Control at AHY, Lee BCH, Chan ASY, Wong JWH, Cheng PSW, Wertheimer T, Velardi E, Tsai J, Cooper K, Xiao S, Kloss Binding and Cleavage of Endogenous RNAs by the mRNA 3‘ Ends. Molecular Cell 70(5):971-982.e6 Chan AKW, Zhang J, Shi J, Fan X, Kwong DLW, Mak TW, CC, Ottmüller KJ, Mokhtari Z, Brede C, deRoos P, Campylobacter jejuni Cas9. Molecular Cell 69(5):893- Yuen ST, Clevers H, Leung SY (2018) A Comprehensive Kinsella S, Palikuqi B, Ginsberg M, Young LF, Kreines F, 905 Kingsley RA, Langridge G, Smith SE, Makendi C, Fookes Human Gastric Cancer Organoid Biobank Captures Lieberman SR, Lazrak A, Guo P, Malard F, Smith OM, M, Wileman TM, El Ghany MA, Keith Turner A, Dyson ZA, Tumor Subtype Heterogeneity and Enables Therapeutic Shono Y, Jenq RR, Hanash AM, Nolan DJ, Butler JM, Leenay RT, Vento JM, Shah M, Martino ME, Leulier F, Sridhar S, Pickard D, Kay S, Feasey N, Wong V, Barquist Screening. Cell Stem Cell 23(6):882-897.e11 Beilhack A 4HUSL` 59 9HÄP : +\KHRV] 1( ]HU KLU Beisel CL (2018) Genome Editing with CRISPR-Cas9 in L, Dougan G (2018) Functional analysis of Salmonella Brink MRM (2018) Production of BMP4 by endothelial Lactobacillus plantarum Revealed That Editing Outcomes Typhi adaptation to survival in water. Environmental Wallaschek N, Niklas C, Pompaiah M, Wiegering A, cells is crucial for endogenous thymic regeneration. Can Vary Across Strains and Between Methods. Microbiology 20(11):4079-4090 Germer CT, Kircher S, Brändlein S, Maurus K, Rosenwald Science Immunology 3(19):eaal2736 Biotechnology Journal 14(3):e1700583 A, Yan HHN, Leung SY, Bartfeld S (2019) Establishing Nolan LM, Whitchurch CB, Barquist L, Katrib M, Boinett 7\YL*HUJLY6YNHUVPK*\S[\YLZ!0KLU[PÄJH[PVU:LSLJ[PVU Medler J, Nelke J, Weisenberger D, Steinfatt T, Rothaug Liao C, Slotkowski RA, Achmedov T, Beisel CL (2018) CJ, Mayho M, Goulding D, Charles IG, Filloux A, Parkhill HUK =LYPÄJH[PVU VM *HUJLY 7OLUV[`WLZ HUK .LUV[`WLZ M, Berr S, Hünig T, Beilhack A, Wajant H (2019) TNFRSF The Francisella novicida Cas12a is sensitive to the J, Cain AK (2018) A global genomic approach uncovers Journal Molecular Biology 431(15):2884-2893 YLJLW[VYZWLJPÄJHU[PIVK`M\ZPVUWYV[LPUZ^P[O[HYNL[PUN structure downstream of the terminal repeat in CRISPR UV]LSJVTWVULU[ZMVY[^P[JOPUNTV[PSP[`TLKPH[LKIPVÄST JVU[YVSSLK -Jф9PUKLWLUKLU[ HNVUPZ[PJ HJ[P]P[` Cell arrays. RNA Biology 16(4):404-412 expansion in Pseudomonas aeruginosa. Microbial Stanifer ML, Mukenhirn M, Muenchau S, Pervolaraki K, Death & Disease 10(3):224 Genomics 4(11):e000229 Kanaya T, Albrecht D, Odendall C, Hielscher T, Haucke Marshall R, Maxwell CS, Collins SP, Jacobsen T, Luo V, Kagan JC, Bartfeld S, Ohno H, Boulant S (2020) Ribechini E, Eckert I, Beilhack A, Du Plessis N, Walzl ML, Begemann MB, Gray BN, January E, Singer A, He Wheeler NE, Gardner PP, Barquist L (2018) Machine (Z`TTL[YPJ KPZ[YPI\[PVU VM ;39 SLHKZ [V H WVSHYPaLK G, Schleicher U, Ritter U, Lutz MB (2019) Heat-killed Y, Beisel CL, Noireaux V (2018) Rapid and Scalable SLHYUPUN PKLU[PÄLZ ZPNUH[\YLZ VM OVZ[ HKHW[H[PVU PU [OL immune response in human intestinal epithelial cells. Mycobacterium tuberculosis prime-boost vaccination *OHYHJ[LYPaH[PVUVM*90:79;LJOUVSVNPLZ

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Schmidt-Hieber M, Engelhard D, Ullmann A, Ljungman Muthinja JM, Ripp J, Krüger T, Imle A, Haraszti T, Fackler ùLSLaUQHR 1 3PZUPDž =1 7VWV]PDž ) 3PZUPDž ) )HIPDž 4 Wagner F, Kunz TC, Chowdhury SR, Thiede B, P, Maertens J, Martino R, Rovira M, Shaw PJ, Robin C, OT, Spatz JP, Engstler M, Frischknecht F (2018) Tailored Halenius A, L‘Hernault A, Roviš TL, Hengel H, Erhard Fraunholz M, Eger D, Kozjak-Pavlovic V (2019) Armadillo Faraci M, Byrne J, Schäfer-Eckart K, Einsele H, Faber E, environments to study motile cells and pathogens. F9LK^VVK(1=PKHS:4+€SRLU32YTWV[PDž(1VUQPDž YLWLH[JVU[HPUPUNWYV[LPUPZHK\HSSVJHSPaH[PVUWYV[LPU Rigacci L, Saccardi R, Balaguer-Rosello A, Isaksson C, Cellular Microbiology 20(3) S (2019) The complex of MCMV proteins and MHC associated with mitochondrial intermembrane space Christopeit M, Tridello G, Wang J, Knelange N, Mikulska class I evades NK cell control and drives the evolution bridging complex. PLoS ONE 14(10):e0218303 M, Cesaro S, Styczynski J (2019) Central nervous system Goos C, Dejung M, Wehman AM, M-Natus E, VM ]PY\ZZWLJPÄJ HJ[P]H[PUN 3`  YLJLW[VYZ Journal of disorders after hematopoietic stem cell transplantation: Schmidt J, Sunter J, Engstler M, Butter F, Kramer S Experimental Medicine 216(8):1809-1827 a prospective study of the Infectious Diseases Working (2019) Trypanosomes can initiate nuclear export co- Party of EBMT. Journal of Neurology 267(2):430-439 transcriptionally. Nucleic Acids Research 47(1):266-282 FROSCH, MATTHIAS

Seif M, Einsele H3€ўLY1 CAR T Cells Beyond :a€͇Y ) :PTVU += 9VQHZ - @V\UN 1 9VIPUZVU +9 FABER, FRANZISKA Frosch M (2018) :PNUPÄJHUJLVM[OLKVJ[VYH[LPUZJPLU[PÄJ Cancer: Hope for Immunomodulatory Therapy of Krüger T, Engstler M, Matthews KR (2019) Positional medical education. Bundesgesundheitsblatt Gesund- Infectious Diseases. Frontiers in Immunology 10:2711 Dynamics and Glycosomal Recruitment of Developmental Bronner DN, Faber F, Olsan EE, Byndloss MX, Sayed heitsforschung Gesundheitsschutz 61(2):141-147 9LN\SH[VYZ K\YPUN ;Y`WHUVZVTL +PќLYLU[PH[PVU mBio NA, Xu G, Yoo W, Kim D, Ryu S, Lebrilla CB, Bäumler AJ Strunz PP, Schmalzing M, Heidemeier A, Rasche 10(4):e00875-19 (2018) .LUL[PJ(ISH[PVUVM)\[`YH[L<[PSPaH[PVU([[LU\H[LZ Moremi N, Claus H, Rutta L, Frosch M, Vogel U, Mshana L, Einsele H, Kortüm KM (2019) Response to Gastrointestinal Salmonella Disease. Cell Host & Microbe SE (2018) High carriage rate of extended-spectrum daratumumab in rituximab-resistant EBV-associated 23(2):266-273.e4 beta-lactamase-producing Enterobacteriaceae among PTLD following allogenic stem cell transplantation from WH[PLU[ZHKTP[[LKMVYZ\YNLY`PU;HUaHUPHUOVZWP[HSZ^P[O an EBV seronegative donor. Leukemia & Lymphoma ERHARD, FLORIAN An SQ, Ding YC, Faber F, Hobley L, Sá-Pessoa J a low rate of endogenous surgical site infections. Journal 60(14):3573-3576 (2019) Social behaviour and making attachments: a of Hospital Infection 100(1):47-53 Erhard F (2018) Estimating pseudocounts and YLWVY[MYVT[OLÄM[O“Young Microbiologists Symposium von Lilienfeld-Toal M, Wagener J, Einsele H, Cornely OA, fold changes for digital expression measurements. on Microbe Signalling, Organisation and Pathogenesis”. Kurzai O (2019) Invasive Fungal Infection. Deutsches Bioinformatics 34(23):4054-4063 Microbiology 165(2):138-145 Ärzteblatt International 116(16):271-278 GASTEIGER, GEORG Erhard F, Halenius A, Zimmermann C, L‘Hernault A, Litvak Y, Mon KKZ, Nguyen H, Chanthavixay G, Liou Wallstabe L, Göttlich C, Nelke LC, Kühnemundt J, Kowalewski DJ, Weekes MP, Stevanovic S, Zimmer R, M, Velazquez EM, Kutter L, Alcantara MA, Byndloss Straub T, Freudenberg MA, Schleicher U, Bogdan C, Schwarz T, Nerreter T, Einsele H, Walles H, Dandekar Dölken L (2018) 0TWYV]LK9PIVZLXLUHISLZPKLU[PÄJH[PVU 4? ;PќHU` *9 >HSRLY .; Faber F, Zhu Y, Bronner Gasteiger G, Pircher H (2018) Bacterial coinfection G, Nietzer SL, Hudecek M (2019) ROR1-CAR T cells are of cryptic translation events. Nature Methods 15(5):363- DN, Byndloss AJ, Tsolis RM, Zhou H, Bäumler AJ restrains antiviral CD8 T-cell response via LPS-induced LќLJ[P]L HNHPUZ[ S\UN HUK IYLHZ[ JHUJLY PU HK]HUJLK 366 (2019) Commensal Enterobacteriaceae Protect against inhibitory NK cells. Nature Communications 9(1):4117 microphysiologic 3D tumor models. JCI Insight 4(18): :HSTVULSSH *VSVUPaH[PVU [OYV\NO 6_`NLU *VTWL[P[PVU 126345 Hennig T, Michalski M, Rutkowski AJ, Djakovic L, Whisnant Cell Host & Microbe 25(1):128-139 Turner JE, Gasteiger G (2018) Innate lymphoid cells: AW, Friedl MS, Jha BA, Baptista MAP, L‘Hernault A, RL` WSH`LYZ PU [PZZ\LZWLJPÄJ PTT\UP[` Seminars in Ward KN, Hill JA, Hubacek P, de la Camara R, Crocchiolo Erhard F, Dölken L, Friedel CC (2018) HSV-1-induced Velazquez EM, Nguyen H, Heasley KT, Saechao CH, Gil Immunopathology 40(4):315-317 R, Einsele H, Navarro D, Robin C, Cordonnier C, disruption of transcription termination resembles a cellular LM, Rogers AWL, Miller BM, Rolston MR, Lopez CA, Litvak Ljungman P, 2017 European Conference on Infections stress response but selectively increases chromatin Y, Liou MJ, Faber F)YVUULY+5;PќHU`*9)`UKSVZZ in Leukaemia (ECIL) (2019) Guidelines from the 2017 accessibility downstream of genes. PLoS Pathogens MX, Byndloss AJ, Bäumler AJ (2019) Endogenous European Conference on Infections in Leukaemia 14(3):e1006954 Enterobacteriaceae underlie variation in susceptibility to GEIBEL, SEBASTIAN for management of HHV-6 infection in patients with Salmonella infection. Nature Microbiology 4(6):1057- hematologic malignancies and after hematopoietic stem Jürges C, Dölken L, Erhard F (2018) Dissecting 1064 Famelis N, Rivera-Calzada A, Degliesposti G, Wingender cell transplantation. Haematologica 104(11):2155-2163 newly transcribed and old RNA using GRAND-SLAM. M, Mietrach N, Skehel JM, Fernandez-Leiro R, Böttcher Bioinformatics 34(13):i218-i226 B, Schlosser A, Llorca O, Geibel S (2019) Architecture Zoran T, Weber M, Springer J, White PL, Bauer J, of the mycobacterial type VII secretion system. Nature :JOVILY ( 3€ўLY * :LLSIPUKLY ) / UUPNLY 2 2\YaHP Vendelova E, Ashour D, Blank P, Erhard F, Saliba AE, FRAUNHOLZ, MARTIN 576(7786):321-325 O, Scherag A, Schäuble S, Morton CO, Einsele H, Kalinke U, Lutz MB (2018) Tolerogenic Transcriptional 3PUKL13€ўLY1 Treatment with etanercept and Signatures of Steady-State and Pathogen-Induced Becker KA, Fahsel B, Kemper H, Mayeres J, Li C, et al., Mietrach N, Schlosser A, Geibel S (2019) An extracellular low monocyte concentration contribute to the risk of Dendritic Cells. Frontiers in Immunology 9:333 Fraunholz M, Gulbins E (2018) Staphylococcus aureus domain of the EsaA membrane component of the type invasive aspergillosis in patients post allogeneic stem cell Alpha-Toxin Disrupts Endothelial-Cell Tight Junctions via =00I ZLJYL[PVU Z`Z[LT! L_WYLZZPVU W\YPÄJH[PVU HUK transplantation. 6FLHQWLðF5HSRUWV 9(1):17231 Wei Y, Corbalán-Campos J, Gurung R, Natarelli L, Zhu Acid Sphingomyelinase and Ceramide. Infection and JY`Z[HSSPaH[PVUActa Crystallographica 75(12):725-730 M, Exner N, Erhard F, Greulich F, Geißler C, Uhlenhaut Immunity 86(1):e00606-17 NH, Zimmer R, Schober A (2018) Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Horn J, Klepsch M, Manger M, Wolz C, Rudel T, Fraunholz ENGSTLER, MARKUS Oxidative Metabolism. Circulation 138(18):2007-2020 M (2018) Long Noncoding RNA SSR42 Controls GOMEZ DE AGÜERO, MERCEDES Staphylococcus aureus Alpha-Toxin Transcription Krüger T, Engstler M (2018) The Fantastic Voyage of the Erhard F, Baptista MAP, Krammer T, Hennig T, Lange M, in Response to Environmental Stimuli. Journal of Fabbiano S, Suárez-Zamorano N, Chevalier C, Trypanosome: A Protean Micromachine Perfected during Arampatzi P, Jürges CS, Theis FJ, Saliba AE, Dölken L Bacteriology 200(22):e00252-18 3HaHYL]PDž = 2PLZLY : 9PNV + 3LV : =L`YH[+\YLIL_ 500 Million Years of Engineering. 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Mooser C, Gomez de Agüero M, Ganal-Vonarburg SC Mufusama JP, Ndjoko Ioset K, Feineis D, Hoellein Becht A, Schollmayer C, Wiest J, Heller D, Baumann W, Zilker M, Sörgel F, Holzgrabe U (2019) A systematic (2018) :[HUKHYKPaH[PVU PU OVZ[TPJYVIPV[H PU[LYHJ[PVU L, Holzgrabe U, Bringmann G (2018) Quality of the Buschmann H, Holzgrabe U (2019) +Pќ\ZPVU VYKLYLK YL]PL^VM[OLZ[HIPSP[`VMÄUPZOLKWOHYTHJL\[PJHSWYVK\J[Z studies: challenges, gnotobiology as a tool, and antimalarial medicine artemether - lumefantrine in 8 cities NMR spectroscopy measurements as screening and drug substances beyond their labeled expiry dates. perspective. Current Opinion in Microbiology 44:50-60 of the Democratic Republic of the Congo. Drug Testing method of potential reactions of API and excipients in Journal of Pharmaceutical and Biomedical Analysis and Analysis 10(10):1599-1606 drug formulations. Journal of Pharmaceutical and 166:222-235 Uchimura Y, Fuhrer T, Li H, Lawson MA, Zimmermann Biomedical Analysis 162:41-46 M, Yilmaz B, Zindel J, Ronchi F, Sorribas M, Hapfelmeier Munz M, Pretscher D, Wilhelm M, Holzgrabe U, Zlotos DP, Mohsen AMY, Mandour YM, Marzouk MA, S, Ganal-Vonarburg SC, Gomez de Agüero M, McCoy Sörgel F, Birkmann J (2018) (aH[OPVWYPULPUK\JLK Götz MR, Collado JA, Fernández-Ruiz J, Fiebich BL, )YLP[PUNLY < =PSSTHUU * )YLP[PUNLY /. :V[YPќLY * KD, Sauer U, Macpherson AJ (2018) Antibodies Set reversible EBV-associated Hodgkin-like lymphoma after García-Toscano L, Gómez-Cañas M, Koch O, Leha A, Jensen AA, Holzgrabe U (2019) 11-Aminostrychnine and Boundaries Limiting Microbial Metabolite Penetration immunosuppressive therapy for autoimmune hepatitis. Muñoz E, Navarrete C, Pazos MR, Holzgrabe U (2019) 5:[Y`JOUPUL`SWYVWPVUHTPKL! :`U[OLZPZ *VUÄN\ and the Resultant Mammalian Host Response. Immunity International Journal of Clinical and :[Y\J[\YL,ќLJ[ 9LSH[PVUZOPWZ VM 5V]LS :LTP:`U[OL[PJ ration, and Pharmacological Evaluation at Glycine Recep- 49(3):545-559.e5 Therapeutics 56(3):142-147 Cannabinoid Derivatives. Frontiers in Pharmacology tors. Journal of Natural Products 82(8):2332-2336 10:1284 Radulovic K, Ayata CK, Mak‘Anyengo R, Lechner K, Rasheed H, Höllein L, Holzgrabe U (2018) Future Wuggenig P, Kaya B, Hruz P, Gomez de Agüero M, Broz Information Technology Tools for Fighting Substandard Parlar S, Sayar G, Tarikogullari AH, Karadagli SS, Alptuzun P, Weigmann B, Niess JH (2019) 5397 +LÄJPLUJ` PU HUK -HSZPÄLK 4LKPJPULZ PU 3V^ HUK 4PKKSL0UJVTL V, Erciyas E, Holzgrabe U (2019) Synthesis, bioactivity KASTENMÜLLER, WOLFGANG CD4 T Cells Decreases T Cell Survival Associated with Countries. Frontiers in Pharmacology 9:995 and molecular modeling studies on potential anti- Increased Cell Death. The Journal of Immunology (SaOLPTLY WPWLYPKPULO`KYHaPKLO`KYHaVULZ Bioorganic )VYZ[1(OYLUKZ;)ǃIHéH54LSPLM*14Kastenmüller 203(2):544-556 Schilling K, Pawellek R, Lovejoy K, Muellner T, Holzgrabe Chemistry 87:888-900 W (2018) CD4+ T cell help in cancer immunology U (2018) 0UÅ\LUJL VM JOHYNLK HLYVZVS KL[LJ[VY and immunotherapy. Nature Reviews Immunology instrument settings on the ultra-high-performance liquid Rasheed H, Hoellein L, Bukhari KS, Holzgrabe U (2019) 18(10):635-647 chromatography analysis of fatty acids in polysorbate 80. Regulatory framework in Pakistan: situation analysis of HERRMANN, THOMAS Journal of Chromatography A 1576:58-66 medicine quality and future recommendations. Journal Breitbach M, Kimura K, Luis TC, Fuegemann CJ, Woll of Pharmaceutical Policy and Practice 12:23 PS, Hesse M, Facchini R, Rieck S, Jobin K, Reinhardt J, Fichtner AS, Karunakaran MM, Starick L, Truman Skaf J, Hamarsheh O, Berninger M, Balasubramanian Ohneda O, Wenzel D, Geisen C, Kurts C, Kastenmüller RW, Herrmann T (2018) The Armadillo (Dasypus S, Oelschlaeger TA, Holzgrabe U (2018) Improving anti- Scherf-Clavel O, Kinzig M, Besa A, Schreiber A, Bidmon W, Hölzel M, Jacobsen SEW, Fleischmann BK (2018) In novemcinctus): A Witness but Not a Functional Example trypanosomal activity of alkamides isolated from Achillea C, Abdel-Tawab M, Wohlfart J, Sörgel F, Holzgrabe U Vivo Labeling by CD73 Marks Multipotent Stromal Cells MVY[OL,TLYNLUJLVM[OL)\[`YVWOPSPU=ф =х:`Z[LT fragrantissima. Fitoterapia 125:191-198 (2019) The contamination of valsartan and other sartans, and Highlights Endothelial Heterogeneity in the Bone in Placental Mammals. Frontiers in Immunology 9:265 Part 2: Untargeted screening reveals contamination with Marrow Niche. Cell Stem Cell 22(2):262-276 Theiss C, Holzgrabe U (2018) *OHYHJ[LYPaH[PVU VM amides additionally to known nitrosamine impurities. Rhodes DA, Chen HC, Williamson JC, Hill A, Yuan J, polydisperse macrogols and macrogol-based excipients Journal of Pharmaceutical and Biomedical Analysis Holland T, Wohlleber D, Marx S, Kreutzberg T, Vento- Smith S, Rhodes H, Trowsdale J, Lehner PJ, Herrmann via HPLC and charged aerosol detection. Journal of 172:278-284 Asturias S, Schmitt-Mbamunyo C, Welz M, Janas M, T, Eberl M (2018) 9LN\SH[PVU VM /\THU фх ; *LSSZ I` Pharmaceutical and Biomedical Analysis 160:212- 2VTHUKLY 2 ,PJROVќ : )YL^P[a ( /HZLUILYN 4 BTN3A1 Protein Stability and ATP-Binding Cassette 221 :JOPSSPUN 2 2YTHY 1 4HSQ\YPDž 5 7H^LSSLR 9 7YV[PDž ( Männ L, Gunzer M, Wilhelm C, Kastenmüller W, Knolle Transporters. Frontiers in Immunology 9:662 Holzgrabe U (2019) Quantitative structure-property P, Abdullah Z, Kurts C, Garbi N (2018) Rescue of T-cell Unger N, Holzgrabe U (2018) Stability and assessment relationship modeling of polar analytes lacking UV function during persistent pulmonary adenoviral infection of amino acids in parenteral nutrition solutions. Journal chromophores to charged aerosol detector response. by Toll-like receptor 9 activation. Journal of Allergy and of Pharmaceutical and Biomedical Analysis 147:125- Analytical and Bioanalytical Chemistry volume Clinical Immunology 141(1):416-419.e10 HOLZGRABE, ULRIKE 139 411(13):2945-2959 >LSa4,PJROVќ:(IK\SSHOA;YLIPJRH1.HY[SHU2/ Balasubramanian S, Skaf J, Holzgrabe U, Bharti R, Volpato D, Holzgrabe U (2018) Designing Hybrids Sörgel F, Kinzig M, Abdel-Tawab M, Bidmon C, Spicer JA, Demetris AJ, Akhlaghi H, Anton M, Manske Förstner KU, Ziebuhr W, Humeida UH, Abdelmohsen UR, Targeting the Cholinergic System by Modulating the Schreiber A, Ermel S, Wohlfart J, Besa A, Scherf-Clavel K, Zehn D, Nieswandt B, Kurts C, Trapani JA, Knolle P, Oelschlaeger TA (2018) A New Bioactive Compound From Muscarinic and Nicotinic Receptors: A Concept to Treat O, Holzgrabe U (2019) The contamination of valsartan Wohlleber D, Kastenmüller W (2018) Perforin inhibition the Marine Sponge-Derived Streptomyces sp. SBT348 (SaOLPTLYºZ+PZLHZL Molecules 23(12):3230 HUK V[OLY ZHY[HUZ 7HY[ ! 5L^ ÄUKPUNZ Journal of protects from lethal endothelial damage during fulminant 0UOPIP[Z :[HWO`SVJVJJHS .YV^[O HUK )PVÄST -VYTH[PVU Pharmaceutical and Biomedical Analysis 172:395- viral hepatitis. Nature Communications 9(1):4805 Frontiers in Microbiology 9:1473 Wahl J, Holzgrabe U (2018) Capillary electrophoresis 405 separation of phenethylamine enantiomers using amino Ataide MA, Kastenmüller W (2019) A Triad of Immune Berninger M, Erk C, Fuß A, Skaf J, Al-Momani E, Israel I, acid based ionic liquids. Journal of Pharmaceutical and Urlaub J, Norwig J, Schollmayer C, Holzgrabe U Cells Promotes Infection. Immunity 51(1):5-7 Raschig M, Güntzel P, Samnick S, Holzgrabe U (2018) Biomedical Analysis 148:245-250 (2019) 1/ 549 HUHS`[PJHS JOHYHJ[LYPaH[PVU VM TPULYHS VPS -S\VYPUL^HSR!;OLPTWHJ[VMÅ\VYPULPUX\PUVSVULHTPKLZVU hydrocarbons (PARAFFINS) for pharmaceutical use. Bachem A, Makhlouf C, Binger KJ, de Souza DP, Tull D, their activity against African sleeping sickness. European Wahl O, Cleynhens J, Verbruggen AM, Holzgrabe U J Pharm Biomed Anal 169:41-48 Hochheiser K, Whitney PG, Fernandez-Ruiz D, Dähling S, Journal of Medicinal Chemistry 152:377-391 (2018) 0TW\YP[` WYVÄSPUN VM 55ºL[O`SLULIPZSJ`Z[LPUL Kastenmüller W, et al., Kallies A, McConville MJ, Turner diethyl ester (Bicisate). Journal of Pharmaceutical and Volpp M, Holzgrabe U (2019) Determination of plasma SJ, Gebhardt T, Bedoui S (2019) Microbiota-Derived El-Hossary EM, Förstner KU, François P, Baud D, Biomedical Analysis 150:132-136 protein binding for sympathomimetic drugs by means Short-Chain Fatty Acids Promote the Memory Potential Streker K, Schrenzel J, Ohlsen K, Holzgrabe U (2018) VM \S[YHÄS[YH[PVU European Journal of Pharmaceutical of Antigen-Activated CD8+ T Cells. Immunity 51(2):285- A Novel Mechanism of Inactivating Antibacterial Nitro Wiest J, Saedtler M, Böttcher B, Grüne M, Reggane Sciences 127:175-184 297.e5 Compounds in the Human Pathogen Staphylococcus M, Galli B, Holzgrabe U, Meinel L (2018) Geometrical aureus by Overexpression of a NADH-Dependent and Structural Dynamics of Imatinib within Biorelevant Wahl J, Holzgrabe U (2019) Enantioseparation by Lämmermann T, Kastenmüller W (2019) Concepts Flavin Nitroreductase. Antimicrobial Agents and Colloids. Molecular Pharmaceutics 15(10):4470-4480 Capillary Electrophoresis Using Cyclodextrins in an Amino of GPCR-controlled navigation in the immune system. Chemotherapy 62(2):e01510-17 (JPK)HZLK 0VUPJ 3PX\PK 9\UUPUN )\ќLY Methods in Immunological Reviews 289(1):205-231 Zilker M, Sörgel F, Holzgrabe U (2018) A stability-study of Molecular Biology 1985:365-371 Monakhova YB, Holzgrabe U, Diehl BWK (2018) expired ampoules manufactured more than 40 years ago. Mondor I, Baratin M, Lagueyrie M, Saro L, Henri S, Gentek Current role and future perspectives of multivariate Journal of Pharmaceutical and Biomedical Analysis Zilker M, Sörgel F, Holzgrabe U (2019) A long-time stability R, Suerinck D, Kastenmüller W 1PHUN 1? )HQtUVќ (chemometric) methods in NMR spectroscopic analysis 150:318-326 study of 50 drug substances representing common M (2019) Lymphatic Endothelial Cells Are Essential of pharmaceutical products. Journal of Pharmaceutical drug classes of pharmaceutical use. Drug Testing and Components of the Subcapsular Sinus Macrophage and Biomedical Analysis 147:580-589 Analysis 11(7):1065-1075 Niche. Immunity 50(6):1453-1466.e4

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Rodríguez-Alcázar JF, Ataide MA, Engels G, Schmitt- Rau M, Schmitt J, Berg T, Kremer AE, Stieger B, Spanaus Wiegand J, Buggisch P, Mauss S, Boeker KHW, Klinker KURZAI, OLIVER Mabmunyo C, Garbi N, Kastenmüller W, Latz E, Franklin K, Bengsch B, Romero MR, Marin JJ, Keitel V, Klinker H, H, Müller T, Günther R, Serfert Y, Manns MP, Zeuzem S, BS (2019) Charcot-Leyden Crystals Activate the NLRP3 Tony HP, Müllhaupt B, Geier A (2018) Serum IP-10 levels Berg T, Hinrichsen H, C-Registry GH (2019) Hepatitis Bloos F, Held J, Schlattmann P, Brillinger N, Kurzai 0UÅHTTHZVTLHUK*H\ZL03у0UÅHTTH[PVUPU/\THU and increased DPPIV activity are linked to circulating C therapy with direct antiviral agents in patients with O, Cornely OA, Thomas-Rüddel D (2018) (у+ Macrophages. Journal of Immunology 202(2):550-558 CXCR3+ T cells in cholestatic HCV patients. PLoS ONE advanced chronic kidney disease: real-world experience glucan-based diagnosis of invasive Candida infection 13(12):e0208225 of the German Hepatitis C-Registry (Deutsches Hepatitis versus culture-based diagnosis in patients with sepsis C-Register). European Journal of Gastroenterology & and with an increased risk of invasive Candida infection Christensen S, Buggisch P, Mauss S, Böker KH, Müller Hepatology 31(11):1424-1431 *HUKP:LW! Z[\K` WYV[VJVS MVY H YHUKVTPaLK JVU[YVSSLK KISKER, CAROLINE T, Klinker H, Zimmermann T, Serfert Y, Weber B, Reimer trial. Trials 19(1):472 J, Wedemeyer H, German Hepatitis C-Registry (2019) Hou JL, Zhao W, Lee C, Hann HW, Peng CY, Tanwandee Giroud M, Dietzel U, Anselm L, Banner D, Kuglstatter A, Alcohol and Cannabis Consumption Does Not Diminish T, Morozov V, Klinker H, Sollano JD, Streinu-Cercel A, et Habbe KJ, Frings A, Schrader S, Roth M, MacKenzie Benz J, Blanc JB, Gaufreteau D, Liu H, Lin X, Stich A, Kuhn Cure Rates in a Real-World Cohort of Chronic Hepatitis al., Sun J, Chen Y, Cooney EL, Lim SG (2020) Outcomes C, Walther G, Kurzai O, Geerling G (2018) Tintelnotia B, Schuler F, Kaiser M, Brun R, Schirmeister T, Kisker C Virus Infected Patients on Opioid Substitution Therapy- of Long-term Treatment of Chronic HBV Infection With destructans: new enemy at the gates. Ophthalmologe C, Diederich F, Haap W (2018) Repurposing a Library of Data From the German Hepatitis C-Registry (DHC-R). ,U[LJH]PYVY6[OLY(NLU[Z-YVTH9HUKVTPaLK;YPHSPU 115(11):948-950 /\THU*H[OLWZPU33PNHUKZ!0KLU[PÄJH[PVUVM4HJYVJ`JSPJ Substance Abuse 13:1178221819835847 Countries. Clinical Gastroenterology and Hepatology Lactams as Potent Rhodesain and Trypanosoma brucei 18(2): 457-467 (Epub 2019) Leo F, Zeh M, Prothmann A, Kurzai O, Kurz S, Grohé C Inhibitors. Journal of Medicinal Chemistry 61(8):3350- .YHM*4VUKVYM(2UVW=7LPќLY2/+PL[a1-YPLZZ1 (2018) Tracheal, laryngeal and pulmonary mucormycosis 3369 Wedemeyer H, Buggisch P, Mauss S, Berg T, Rausch M, Tacke F, Boeker KHW, Klinker H, Heyne R, Buggisch MVSSV^LKI`VYNHUPaPUNWUL\TVUPHPUHWH[PLU[^P[O(K\S[ Sprinzl M, Klinker H, Hinrichsen H, Bronowicki JP, Haag P, Pathil A, Wiegand J, Cornberg M, Lange C, Berg Onset Still‘s Disease. Medical Mycology Case Reports Grabarczyk DB, Silkenat S, Kisker C (2018) Structural S, Hüppe D, Lutz T, Poynard T, Zeuzem S, Friedrich-Rust T, Zeuzem S, Mauss S (2020) Baseline risk factors 20:28-32 Basis for the Recruitment of Ctf18-RFC to the Replisome. M, Sarrazin C, Vermehren J (2019) Evaluation of Point determine lack of biochemical response after SVR in Structure 26(1):137-144.e3 Shear Wave Elastography Using Acoustic Radiation Force chronic hepatitis C patients treated with DAAs. Liver Geißel B, Loiko V, Klugherz I, Zhu Z, Wagener N, Kurzai Impulse Imaging for Longitudinal Fibrosis Assessment in International 40(3):539-548 (Epub 2019) O, van den Hondel CAMJJ, Wagener J (2018) (aVSL Ramirez YA, Adler TB, Altmann E, Klemm T, Tiesmeyer Patients with HBeAg-Negative HBV Infection. Journal of induced cell wall carbohydrate patches kill Aspergillus *:H\LY-2H[OTHU:.:[H[Z`\R(=:V[YPќLY*Kisker Clinical Medicine 8(12):2101 Yuen MF, Schiefke I, Yoon JH, Ahn SH, Heo J, Kim JH, fumigatus. Nature Communications 9(1):3098 C (2018) Structural Basis of Substrate Recognition and Chan HLY, Yoon KT, Klinker H, Manns M, Petersen Covalent Inhibition of Cdu1 from Chlamydia trachomatis. Hüppe D, Serfert Y, Buggisch P, Mauss S, Böker KHW, J, Schluep T, Hamilton J, Given BD, Ferrari C, Lai CL, Morton CO, Wurster S, Fliesser M, Ebel F, Page L, ChemMedChem 13(19):2014-2023 Müller T, Klinker H, Günther R, Berg T, Cornberg M, Locarnini SA, Gish RG (2020) RNA Interference Therapy Hünniger K, Kurzai O, Schmitt AL, Michel D, Springer Niederau C, Sarrazin C, Simon KG, Zeuzem S, Manns MP, with ARC-520 Results in Prolonged HBsAg Response in 1,PUZLSL/3VLўLY1 =HSPKH[PVUVMHZPTWSPÄLKPU Nasir N, Kisker C (2019) Mechanistic insights into Wedemeyer H (2019) 4 years of direct-acting antivirals Patients with Chronic Hepatitis B Infection. Hepatology vitro Transwell® model of the alveolar surface to assess [OL LUa`TH[PJ HJ[P]P[` HUK PUOPIP[PVU VM [OL YLWSPJH[P]L (DAAs) in the German Hepatitis C-Registry (DHC-R). 72(1):19-31 (Epub 2019) OVZ[ PTT\UP[` PUK\JLK I` KPќLYLU[ TVYWOV[`WLZ VM polymerase exonuclease domain from Mycobacterium Zeitschrift für Gastroenterologie 57(1):27-36 Aspergillus fumigatus. International Journal of Medical tuberculosis. DNA Repair 74:17-25 Microbiology 308(8):1009-1017 Knop V, Hofmann WP, Buggisch P, Klinker H, Mauss S, Sauer F, Klemm T, Kollampally RB, Tessmer I, Nair RK, . U[OLY9/PUYPJOZLU// WWL+7MLPќLY=VYURHOS/ KOZJAK-PAVLOVIC, VERA Polke M, Leonhardt I, Kurzai O, Jacobsen ID (2018) Popov N, Kisker C (2019) +PќLYLU[PHS6SPNVTLYPaH[PVUVM Simon KG, Berg T, Manns MP, Friedrich-Rust M; German Farnesol signalling in Candida albicans - more than just the Deubiquitinases USP25 and USP28 Regulates Their Hepatitis C-Registry (2019) ,Z[PTH[PVU VM SP]LY ÄIYVZPZ Arroyo-Olarte RD, Thurow L, Kozjak-Pavlovic V, Gupta communication. Critical Reviews in Microbiology Activities. Molecular Cell 74(3):421-435.e10 by noncommercial serum markers in comparison with N (2018) Illuminating pathogen-host intimacy through 44(2):230-243 transient elastography in patients with chronic hepatitis C optogenetics. PLoS Pathogens 14(7):e1007046 virus infection receiving direct-acting antiviral treatment. Prauße MTE, Lehnert T, Timme S, Hünniger K, Leonhardt Journal of Viral Hepatitis 26(2):224-230 Huang X, Wu BP, Nguyen D, Liu YT, Marani M, Hench I, Kurzai O, Figge MT (2018) Predictive Virtual Infection KLINKER, HARTWIG J, Bénit P, Kozjak-Pavlovic V, Rustin P, Frank S, Modeling of Fungal Immune Evasion in Human Whole Krüger K, Krauth C, Rossol S, Mauss S, Boeker KHW, Narendra DP (2018) CHCHD2 accumulates in distressed Blood. Frontiers in Immunology 9:560 Christensen S, Buggisch P, Mauss S, Böker KHW, Schott Müller T, Klinker H, Pathil A, Heyne R, Stahmeyer JT, TP[VJOVUKYPHHUKMHJPSP[H[LZVSPNVTLYPaH[PVUVM*/*/+ E, Klinker H, Zimmermann T, Weber B, Reimer J, Serfert Collaborators DHC-R (2019) Outcomes and costs of Human Molecular Genetics 27(22):3881-3900 Ruhnke M, Behre G, Buchheidt D, Christopeit M, Y, Wedemeyer H (2018) Direct-acting antiviral treatment treating hepatitis C patients with second-generation Hamprecht A, Heinz W, Heussel CP, Horger M, Kurzai of chronic HCV-infected patients on opioid substitution direct-acting antivirals: results from the German Hepatitis Kozjak-Pavlovic V, Herweg JA, Rudel T (2018) The O 2HY[OH\Z 4 3€ўLY 1 et al., Schwartz S, Ullmann therapy: Still a concern in clinical practice? Addiction C-Registry. European Journal of Gastroenterology & role of host cell organelles in the development of A, Vehreschild JJ, von Lilienfeld-Toal M, Weber T, 113(5):868-882 Hepatology 31(2):230-240 Simkania negevensis. International Journal of Medical Wolf HH (2018) Diagnosis of invasive fungal diseases Microbiology 308(1):155-160 in haematology and oncology: 2018 update of the Höner Zu Siederdissen C, Buggisch P, Böker K, Schott E, Sarrazin C, Buggisch P, Mauss S, Müller T, Zimmermann recommendations of the infectious diseases working Klinker H7H[OPS(7MLPќLY=VYURHOS/)LYN;:HYYHaPU T, Klinker H, Pathil-Warth A, Schlag M, Nalpas C, Wegner Heydarian M, Yang T, Schweinlin M, Steinke M, Walles party of the German society for hematology and medical C, Hüppe D, Manns MP, Mauss S (2018) Treatment of S, Lonjon-Domanec I, Simon KG (2019) Evolution of H, Rudel T, Kozjak-Pavlovic V (2019) Biomimetic oncology (AGIHO). Mycoses 61(11):796-813 OLWH[P[PZ*NLUV[`WLPUMLJ[PVUPU.LYTHU`!LќLJ[P]LULZZ HCV patient characteristics and DAA regimens in the Human Tissue Model for Long-Term Study of Neisseria and safety of antiviral treatment in a real-world setting. German Hepatitis C Registry (DHC-R) in 2014 and 2015. gonorrhoeae Infection. Frontiers in Microbiology Timme S, Lehnert T, Prauße MTE, Hünniger K, Leonhardt United European Gastroenterology Journal 6(2):213- Zeitschrift für Gastroenterologie 57(5):584-592 10:1740 I, Kurzai O, Figge MT (2018) Quantitative Simulations 224 Predict Treatment Strategies Against Fungal Infections in :JOpMLY . /VќTHUU * (YHZ[LO 2 et al., Klinker H, Kunz TC, Kozjak-Pavlovic V (2019) Diverse Facets of Virtual Neutropenic Patients. Frontiers in Immunology Schultheiß M, Kling S, Lenker U, von Bibra M, Rosenkranz Härter G, Stöhr A, Degen O, Freiwald E, Hüfner A, Jordan Sphingolipid Involvement in Bacterial Infections. Frontiers 9:667 B, Klinker H (2018) Lopinavir serum concentrations of S, Schulze Zur Wiesch J, Addo M, Lohse AW, van Lunzen in Cell and Developmental Biology 7:203 critically ill infants: a pharmacokinetic investigation in J, Schmiedel S, IDEAL study group (2019) Immediate Voltersen V, Blango MG, Herrmann S, Schmidt F, et al., South Africa. Medical Microbiology and Immunology versus deferred antiretroviral therapy in HIV-infected Wagner F, Kunz TC, Chowdhury SR, Thiede B, Fraunholz 3€ўLY12YHWWTHUU:5PL[aZJOL:Kurzai O, Einsele 207(5-6):339-343 WH[PLU[Z WYLZLU[PUN ^P[O HJ\[L (0+:KLÄUPUN L]LU[Z M, Eger D, Kozjak-Pavlovic V (2019) Armadillo repeat- H, Kniemeyer O, Filler SG, Reichard U, Brakhage AA (toxoplasmosis, Pneumocystis jirovecii-pneumonia): a JVU[HPUPUN WYV[LPU  PZ H K\HS SVJHSPaH[PVU WYV[LPU (2018) Proteome Analysis Reveals the Conidial Surface WYVZWLJ[P]L YHUKVTPaLK VWLUSHILS T\S[PJLU[LY Z[\K` associated with mitochondrial intermembrane space Protein CcpA Essential for Virulence of the Pathogenic (IDEAL-study). AIDS Research and Therapy 16(1):34 bridging complex. PLoS ONE 14(10):e0218303 Fungus Aspergillus fumigatus. mBio 9(5):e01557-18

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Weber M, Schaer J, Walther G, Kaerger K, Steinmann J, Springer J, Walther G, Rickerts V, Hamprecht A, Willinger Lauruschkat CD, Wurster S, Page L, Lazariotou M, Voltersen V, Blango MG, Herrmann S, Schmidt F, et al., Rath PM, Spiess B, Buchheidt D, Hamprecht A, Kurzai B, Teschner D, Einsele H, Kurzai O 3VLўLY 1   Dragan M, Weis P, Ullmann AJ, Einsele H, /ŌυHU- (2018) >LPZZ,/ UUPNLY23P\//VY[ZJOHUZR`7:JOLќVSK( O (2018) FunResDB-A web resource for genotypic Detection of Fusarium Species in Clinical Specimens by :\ZJLW[PIPSP[` VM ( M\TPNH[\ZZWLJPÄJ ;JLSS HZZH`Z [V /ŌυHU-, Krappmann S, Nietzsche S, Kurzai O, Einsele susceptibility testing of Aspergillus fumigatus. Medical Probe-Based Real-Time PCR. Journal of Fungi (Basel) pre-analytic blood storage and PBMC cryopreservation H, Kniemeyer O, Filler SG, Reichard U, Brakhage AA Mycology 56(1):117-120 5(4):105 greatly depends on readout platform and analytes. (2018) Proteome Analysis Reveals the Conidial Surface Mycoses 61(8):549-560 Protein CcpA Essential for Virulence of the Pathogenic Weiss E, Ziegler S, Fliesser M, Schmitt AL, Hünniger Vivas W, Leonhardt I, Hünniger K, Häder A, Marolda A, Fungus Aspergillus fumigatus. mBio 9(5):e01557-18 K, Kurzai O 4VY[VU *6 ,PUZLSL / 3VLўLY 1   Kurzai O (2019) Multiple Signaling Pathways Involved Lauruschkat CD, Einsele H, /ŌυHU - (2018) First Insights in NK-DC Cross-Talk and the Importance PU/\THU+LUKYP[PJ*LSS4H[\YH[PVU(YL(ќLJ[LKI`[OL Immunomodulation as a Therapy for Aspergillus Infection: Weiss E, Ziegler S, Fliesser M, Schmitt AL, Hünniger of Soluble Factors During Infection with Aspergillus Fungal Quorum-Sensing Molecule Farnesol. Journal of Current Status and Future Perspectives. Journal of K, Kurzai O, Morton CO, Einsele H, /ŌυHU - (2018) fumigatus. Frontiers in Cellular and Infection Immunology 203(11):2959-2969 Fungi (Basel) 4(4):137 First Insights in NK-DC Cross-Talk and the Importance Microbiology 8:288 of Soluble Factors During Infection With Aspergillus von Lilienfeld-Toal M, Wagener J, Einsele H, Cornely OA, /ŌυHU-, Ebel F (2018) :PaLTH[[LYZOV^[OLPTT\UL fumigatus. Frontiers in Cellular and Infection Al-Zaben N, Medyukhina A, Dietrich S, Marolda A, Kurzai O (2019) Invasive Fungal Infection. Deutsches system deals with fungal hyphae. Microbes and Microbiology 8:288 Hünniger K, Kurzai O, Figge MT (2019) Automated Ärzteblatt International 116(16):271-278 Infection 20(9-10):521-525 tracking of label-free cells with enhanced recognition of Belic S, Page L, Lazariotou M, Waaga-Gasser AM, whole tracks. 6FLHQWLðF5HSRUWV 9(1):3317 Wagner L, de Hoog S, Alastruey-Izquierdo A, Voigt K, Marischen L, Englert A, Schmitt AL, Einsele H, /ŌυHU Dragan M, Springer J, /ŌυHU-, Morton CO, Einsele H, Kurzai O, Walther G (2019) A Revised Species Concept J (2018) Human NK cells adapt their immune response Ullmann AJ, Wurster S (2019) Comparative Analysis of Barber AE, Weber M, Kaerger K, Linde J, Gölz H, for Opportunistic Mucor Species Reveals Species- towards increasing multiplicities of infection of Aspergillus 0UÅHTTH[VY` *`[VRPUL 9LSLHZL HUK (S]LVSHY ,WP[OLSPHS Duerschmied D, Markert A, Guthke R, Walther G, :WLJPÄJ (U[PM\UNHS :\ZJLW[PIPSP[` 7YVÄSLZ Antimicrobial fumigatus. BMC Immunology 19(1):39 Barrier Invasion in a Transwell® Bilayer Model of Kurzai O (2019) Comparative Genomics of Serial Agents and Chemotherapy 63(8):e00653-19 Mucormycosis. Frontiers in Microbiology 9:3204 Candida glabrata Isolates and the Rapid Acquisition of Morton CO, Wurster S, Fliesser M, Ebel F, Page L, Echinocandin Resistance during Therapy. Antimicrobial Walther G, Wagner L, Kurzai O (2019) Outbreaks of Hünniger K, Kurzai O, Schmitt AL, Michel D, Springer Hoenigl M, Orasch T, Faserl K, Prattes J, /ŌυHU -, Agents and Chemotherapy 63(2):e01628-18 Mucorales and the Species Involved. Mycopathologia J, Einsele H, /ŌυHU- (2018) =HSPKH[PVUVMHZPTWSPÄLKPU Springer J, Gsaller F, Reischies F, Duettmann W, Raggam doi: 10.1007/s11046-019-00403-1 vitro Transwell® model of the alveolar surface to assess RB, Lindner H, Haas H (2019) Triacetylfusarinine C: A /HTWYLJO[ ( )HYILY (, 4LSSPUNOVќ :* ;OLSLU 7 OVZ[ PTT\UP[` PUK\JLK I` KPќLYLU[ TVYWOV[`WLZ VM urine biomarker for diagnosis of invasive aspergillosis. Walther G, Yu Y, Neurgaonkar P, Dandekar T, Cornely OA, Walther G, Wagner L, Kurzai O (2019) Updates on the Aspergillus fumigatus. International Journal of Medical Journal of Infection 78(2):150-157 Martin R, Kurzai O, German Candida auris Study Group Taxonomy of Mucorales with an Emphasis on Clinically Microbiology 308(8):1009-1017 (2019) Candida auris in Germany and Previous Exposure Important Taxa. Journal of Fungi (Basel) 5(4):106 Seif M, Einsele H, /ŌυHU- (2019) CAR T Cells Beyond to Foreign Healthcare. Emerging Infectious Diseases Page L, Weis P, Müller T, Dittrich M, Lazariotou M, Dragan Cancer: Hope for Immunomodulatory Therapy of 25(9):1763-1765 Zoran T, Weber M, Springer J, White PL, Bauer J, M, Waaga-Gasser AM, Helm J, Dandekar T, Einsele H, Infectious Diseases. Frontiers in Immunology 10:2711 :JOVILY(3€ўLY*:LLSIPUKLY)/ UUPNLY2Kurzai /ŌυHU -, Ullmann AJ, Wurster S (2018) Evaluation of Hünniger K, Kurzai O (2019) Phagocytes as central O, Scherag A, Schäuble S, Morton CO, Einsele H, (ZWLYNPSS\ZHUK4\JVYHSLZZWLJPÄJ;JLSSZHUKWLYPWOLYHS Springer J, McCormick Smith I, Hartmann S, Winkelmann players in the defence against invasive fungal infection. 3PUKL13€ўLY1 Treatment with etanercept and blood mononuclear cell cytokine signatures as biomarkers R, Wilmes D, Cornely O, Kessel J, /ŌυHU -, Rickerts Seminars in Cell & Developmental Biology 89:3-15 low monocyte concentration contribute to the risk of of environmental mold exposure. International Journal V (2019) 0KLU[PÄJH[PVU VM (ZWLYNPSS\Z HUK 4\JVYHSLZ invasive aspergillosis in patients post allogeneic stem cell of Medical Microbiology 308(8):1018-1026 PU MVYTHSPUÄ_LK WHYHѝULTILKKLK [PZZ\L ZHTWSLZ! Koehler P, Arendrup MC, Arikan-Akdagli S, Bassetti M, transplantation. 6FLHQWLðF5HSRUWV9(1):17231 *VTWHYPZVU VM ZWLJPÄJ HUK IYVHKYHUNL M\UNHS X7*9 Bretagne S, Klingspor L, Lagrou K, Meis JF, Rautemaa- Ruhnke M, Behre G, Buchheidt D, Christopeit M, assays. Medical Mycology 57(3):308-313 Richardson R, Schelenz S, Hamprecht A, Koehler FC, Wagner L, Stielow JB, de Hoog GS; Bensch K, Schwartze Hamprecht A, Heinz W, Heussel CP, Horger M, Kurzai O, Kurzai O, Salmanton-García J, Vehreschild JJ, Alanio VU, Voigt K, Alastruey-Izquierdo A, Kurzai O, Walther G. Karthaus M, /ŌυHU-, Maschmeyer G, Penack O, Rieger Springer J, Walther G, Rickerts V, Hamprecht A, Willinger A, Alastruey-Izquierdo A, Arsic Arsenijevic V, Gangneux (2020) A new species concept for the clinically relevant C, Rickerts V, Ritter J, Schmidt-Hieber M, Schuelper N, B, Teschner D, Einsele H, Kurzai O, /ŌυHU - (2019) JP, Gow NAR, Hadina S, Hamal P, Johnson E, Klimko Mucor circinelloides complex. Persoonia 44:67-97(31) Schwartz S, Ullmann A, Vehreschild JJ, von Lilienfeld-Toal Detection of Fusarium Species in Clinical Specimens by N, Lass-Flörl C, Mares M, Özenci V, Papp T, Roilides E, (Epub 2019) M, Weber T, Wolf HH (2018) Diagnosis of invasive fungal Probe-Based Real-Time PCR. J Fungi (Basel) 5(4):105 Sabino R, Segal E, Talento AF, Tortorano AM, Verweij diseases in haematology and oncology: 2018 update of PE, Hoenigl M, Cornely OA, European Confederation of the recommendations of the infectious diseases working Srivastava M, Bencurova E, Gupta SK, Weiss E, /ŌυHU Medical Mycology (ECMM) (2019) ECMM CandiReg-A party of the German society for hematology and medical J, Dandekar T (2019) Aspergillus fumigatus Challenged ready to use platform for outbreaks and epidemiological LÖFFLER, JÜRGEN oncology (AGIHO). Mycoses 61(11):796-813 by Human Dendritic Cells: Metabolic and Regulatory studies. Mycoses 62(10):920-927 Pathway Responses Testify a Tight Battle. Frontiers in Barnes RA, White PL, Morton CO, Rogers TR, Cruciani M, Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning Cellular and Infection Microbiology 9:168 Nesseler A, Schauerte N, Geiger C, Kaerger K, Walther /ŌυHU-, Donnelly JP (2018) Diagnosis of aspergillosis by DW, Groll AH, Lagrou K, Lass-Flörl C, Lewis RE, Munoz G, Kurzai O, Eisenberg T (2019) Sporothrix humicola PCR: Clinical considerations and technical tips. Medical P, Verweij PE, Warris A, Ader F, Akova M, Arendrup Zoran T, Weber M, Springer J, White PL, Bauer J, (Ascomycota: Ophiostomatales) - A soil-borne fungus Mycology 56(suppl_1):60-72 MC, Barnes RA, Beigelman-Aubry C, Blot S, Bouza E, :JOVILY ( 3€ўLY * :LLSIPUKLY ) / UUPNLY 2 2\YaHP with pathogenic potential in the eastern quoll (Dasyurus Brüggemann RJM, Buchheidt D, Cadranel J, Castagnola O, Scherag A, Schäuble S, Morton CO, Einsele H, viverrinus). Medical Mycology Case Reports 25:39-44 Caetano LA, Faria T, Springer J, /ŌυHU -, Viegas C E, Chakrabarti A, Cuenca-Estrella M, Dimopoulos G, Linde J, /ŌυHU- (2019) Treatment with etanercept and (2018) (U[PM\UNHSYLZPZ[HU[ 4\JVYHSLZ PU KPќLYLU[ PUKVVY Fortun J, Gangneux JP, Garbino J, Heinz WJ, Herbrecht low monocyte concentration contribute to the risk of Roth M, Daas L, Renner-Wilde A, Cvetkova-Fischer environments. Mycology 10(2):75-83 R, Heussel CP, Kibbler CC, Klimko N, Kullberg BJ, Lange invasive aspergillosis in patients post allogeneic stem cell N, Saeger M, Herwig-Carl M, Matthaei M, Fekete A, C, Lehrnbecher T, /ŌυHU -, Lortholary O, Maertens J, transplantation. 6FLHQWLðF5HSRUWV 9(1):17231 Kakkassery V, Walther G, von Lilienfeld-Toal M, Mertens Decker C, Wurster S, Lazariotou M, Hellmann AM, Einsele Marchetti O, Meis JF, Pagano L, Ribaud P, Richardson C, Lenk J, Mehlan J, Fischer C, Fuest M, Kroll S, Bayoudh H, Ullmann AJ, /ŌυHU - (2018) Analysis of the in vitro M, Roilides E, Ruhnke M, Sanguinetti M, Sheppard DC, Gits-Muselli M, White PL, Mengoli C, Chen S, Crowley W, Viestenz A, Frings A, MacKenzie CR, Messmer EM, activity of human neutrophils against Aspergillus fumigatus Sinkó J, Skiada A, Vehreschild MJGT, Viscoli C, Cornely B, Dingemans G, Fréalle E, L Gorton R, Guiver M, Hagen Seitz B, Kurzai O, Geerling G. (2019) The German in presence of antifungal and immunosuppressive agents. OA (2018) Diagnosis and management of Aspergillus F, et al., Scherer E, Steinmann J, Cruciani M, Barnes keratomycosis registry: Initial results of a multicenter Medical Mycology 56(4):514-519 diseases: executive summary of the 2017 ESCMID- R, Donnelly JP, /ŌυHU -, Bretagne S, Alanio A (2020) survey. Ophthalmologe 116(10):957-966 ECMM-ERS guideline. Clinical Microbiology and The Fungal PCR Initiative‘s evaluation of in-house and Infection 24 (Suppl1):e1-e38 commercial Pneumocystis jirovecii qPCR assays: Toward a standard for a diagnostics assay. Medical Mycology 58(6):779-788 (Epub 2019)

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LUTZ, MANFRED :JOTP[a ; :JO^LPUSPU 4 2VSSOVќ 9; ,UNLSOHYK[ 3 Nishimoto AT, Wiederhold NP, Flowers SA, Zhang Q, OHLSEN, KNUT Lotz C, Groeber-Becker F, Walles H, Metzger M Kelly SL, Morschhäuser J, Yates CM, Hoekstra WJ, Löhr M, Freitag B, Technau A, Krauss J, Monoranu (2018) Nanostructured TiN-Coated Electrodes for High- Schotzinger RJ, Garvey EP, Rogers PD (2019) In Vitro Bruchhagen C, Jarick M, Mewis C, Hertlein T, Niemann CM, Rachor J, Lutz MB, Hagemann C, Kessler AF, :LUZP[P]P[`5VUPU]HZP]L*OHYHJ[LYPaH[PVUVMPU=P[YV;PZZ\L (J[P]P[PLZ VM [OL 5V]LS 0U]LZ[PNH[PVUHS ;L[YHaVSLZ =; S, Ohlsen K, Peters G, Planz O, Ludwig S, Ehrhardt C 3PUZLUTHUU ; >€SÅ 4 ,YULZ[\Z 90 ,UNLSOHYK[ : Models. 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Nguyen MT, Saising J, Tribelli PM, Nega M, Diene SM, Prusty BK, Gulve N, Chowdhury SR, Schuster M, Strempel Kunz TC, Götz R, Sauer M, Rudel T (2019) Detection of Hollenhorst MI, Jurastow I, Nandigama R, Appenzeller S, François P, Schrenzel J, Spröer C, Bunk B, Ebner P, Hertlein S, Descamps V, Rudel T (2018) HHV-6 encoded small *OSHT`KPH+L]LSVWTLU[HS-VYTZHUK:LJYL[LK,ќLJ[VYZ Li L, Vogel J, et al., Altmüller J, Hirsch AKH, Flockerzi T, Kumari N, Härtner T, Wistuba D, Voravuthikunchai SP, UVUJVKPUN95(ZKLÄULHUPU[LYTLKPH[LHUKLHYS`Z[HNL by Expansion Microscopy. Frontiers in Cellular and V, Canning BJ, Saliba AE, Krasteva-Christ G. (2020) Mäder U, Ohlsen K, Götz F (2019) Inactivation of farR in viral reactivation. NPJ Genomic Medicine 3:25 Infection Microbiology 9:276 Tracheal brush cells release acetylcholine in response Causes High Rhodomyrtone Resistance and Increased to bitter tastants for paracrine and autocrine signaling. Pathogenicity in Staphylococcus aureus. Frontiers in Haas A, Hensel M, Lührmann A, Rudel T, Saftig P, Schaible Rother M, Teixeira da Costa AR, Zietlow R, Meyer TF, Federation of American Societies for Experimental Microbiology 10:1157 UE (2018) Intracellular compartments of pathogens: Rudel T (2019) Modulation of Host Cell Metabolism by Biology Journal 34(1):316-332 Highways to hell or stairways to heaven? International Chlamydia trachomatis. Microbiology Spectrum 7(3) Seethaler M, Hertlein T, Wecklein B, Ymeraj A, Ohlsen Journal of Medical Microbiology 308(1):1-2 K, Lalk M, Hilgeroth A (2019) Novel Small-molecule Yang M, Rajeeve K, Rudel T, Dandekar T (2019) Antibacterials against Gram-positive Pathogens of Horn J, Klepsch M, Manger M, Wolz C, Rudel T, Fraunholz Comprehensive Flux Modeling of Chlamydia trachomatis SCHNEIDER-SCHAULIES, JÜRGEN Staphylococcus and Enterococcus Species. Antibiotics M (2018) Long Noncoding RNA SSR42 Controls Proteome and qRT-PCR Data Indicate Biphasic Metabolic 8(4):210 Staphylococcus aureus Alpha-Toxin Transcription +PќLYLUJLZ )L[^LLU ,SLTLU[HY` )VKPLZ HUK 9L[PJ\SH[L Schneider-Schaulies J, Beyersdorf N (2018) CD4+ in Response to Environmental Stimuli. Journal of Bodies During Infection. Front Microbiol 10:2350 Foxp3+ regulatory T cell-mediated immunomodulation Trübe P, Hertlein T, Mrochen DM, Schulz D, Jorde I, Bacteriology 200(22):e00252-18 by anti-depressants inhibiting acid sphingomyelinase. Krause B, Zeun J, Fischer S, Wolf SA, Walther B, Semmler Biological Chemistry 399(10):1175-1182 T, Bröker BM, Ulrich RG, Ohlsen K, Holtfreter S (2019) Horn J, Stelzner K, Rudel T, Fraunholz M (2018) Inside )YPUNPUN [VNL[OLY ^OH[ ILSVUNZ [VNL[OLY! 6W[PTPaPUN job: Staphylococcus aureus host-pathogen interactions. SALIBA, ANTOINE-EMMANUEL Tiwarekar V, Wohlfahrt J, Fehrholz M, Scholz CJ, Kneitz murine infection models by using mouse-adapted International Journal of Medical Microbiology S, Schneider-Schaulies J (2018) APOBEC3G-Regulated Staphylococcus aureus strains. International Journal of 308(6):607-624 Cochain C, Vafadarnejad E, Arampatzi P, Pelisek J, Host Factors Interfere with Measles Virus Replication: Role Medical Microbiology 309(1):26-38 Winkels H, Ley K, Wolf D, Saliba AE, Zernecke A of REDD1 and Mammalian TORC1 Inhibition. Journal of Kozjak-Pavlovic V, Herweg JA, Rudel T (2018) The (2018) Single-Cell RNA-Seq Reveals the Transcriptional Virology 92(17):e00835-18 role of host cell organelles in the development of Landscape and Heterogeneity of Aortic Macrophages Simkania negevensis. International Journal of Medical in Murine Atherosclerosis. Circulation Research Grafen A, Schumacher F, Chithelen J, Kleuser B, PÉREZ, CHRISTIAN Microbiology 308(1):155-160 122(12):1661-1674 Beyersdorf N, Schneider-Schaulies J (2019) Use of Acid Ceramidase and Sphingosine Kinase Inhibitors del Olmo Toledo V, Puccinelli R, Fordyce PM, Pérez JC Nadella V, Mohanty A, Sharma L, Yellaboina S, Mollenkopf Müller LSM, Cosentino RO, Förstner KU, Guizetti J, as Antiviral Compounds Against Measles Virus (2018) +P]LYZPÄJH[PVUVM+5(IPUKPUNZWLJPÄJP[PLZLUHISLK HJ, Mazumdar VB, Palaparthi R, Mylavarapu MB, Maurya Wedel C, Kaplan N, Janzen CJ, Arampatzi P, Vogel J, Infection of Lymphocytes in vitro. Frontiers in Cell and SREBP transcription regulators to expand the repertoire R, Kurukuti S, Rudel T, Prakash H (2018) Inhibitors Steinbiss S, Otto TD, Saliba AE, Sebra RP, Siegel TN Developmental Biology 7:218 of cellular functions that they govern in fungi. PLoS of Apoptosis Protein Antagonists (Smac Mimetic (2018) .LUVTL VYNHUPaH[PVU HUK +5( HJJLZZPIPSP[` Genetics 14(12):e1007884 *VTWV\UKZ*VU[YVS7VSHYPaH[PVUVM4HJYVWOHNLZK\YPUN control antigenic variation in trypanosomes. Nature Hollmann C, Wiese T, Dennstädt F, Fink J, Schneider- 4PJYVIPHS*OHSSLUNLHUK:[LYPSL0UÅHTTH[VY`9LZWVUZLZ 563(7729):121-125 Schaulies J, Beyersdorf N (2019) Translational Meir J, Hartman E, Eckstein MT, Guiducci E, Kirchner Frontiers in Immunology 8:1792 Approaches Targeting Ceramide Generation From F, Rosenwald A, LeibundGut-Landmann S, Pérez JC Pezoldt J, Pasztoi M, Zou M, Wiechers C, Beckstette Sphingomyelin in T Cells to Modulate Immunity in (2018) 0KLU[PÄJH[PVUVM*HUKPKHHSIPJHUZYLN\SH[VY`NLULZ Prusty BK, Chowdhury SR, Gulve N, Rudel T (2018) M, Thierry GR, Vafadarnejad E, Floess S, Arampatzi Humans. Frontiers in Immunology 10:2363 governing mucosal infection. Cellular Microbiology Peptidase Inhibitor 15 (PI15) Regulates Chlamydial P, Buettner M, Schweer J, Fleissner D, Vital M, Pieper 20(8):e12841 CPAF Activity. Frontiers in Cellular and Infection DH, Basic M, Dersch P, Strowig T, Hornef M, Bleich Tiwarekar V, Fehrholz M, Schneider-Schaulies J (2019) Microbiology 8:183 ( )VKL < 7HIZ[ < )HQtUVќ 4 Saliba AE, Huehn J KDELR2 Competes with Measles Virus Envelope Proteins Cottier F, Sherrington S, Cockerill S, del Olmo Toledo V, (2018) Neonatally imprinted stromal cell subsets induce for Cellular Chaperones Reducing Their Chaperone- Kissane S, Tournu H, Orsini L, Palmer GE, Pérez JC, Hall Rajeeve K, Das S, Prusty BK, Rudel T (2018) Chlamydia tolerogenic dendritic cells in mesenteric lymph nodes. Mediated Cell Surface Transport. Viruses 11(1):27 RA (2019) 9LTHZRPUN VM *HUKPKH HSIPJHUZ у.S\JHU PU trachomatis paralyses neutrophils to evade the host Nature Communications 9(1):3903 Response to Environmental pH Is Regulated by Quorum innate immune response. Nature Microbiology 3(7):824- Sensing. mBio 10(5):e02347-19 835 Stapels DAC, Hill PWS, Westermann AJ, Fisher RA, Thurston TL, Saliba AE, Blommestein I, Vogel J, SCHNEIDER-SCHAULIES, SIBYLLE Pérez JC (2019) T:WOLYL VM 0UÅ\LUJL! H :`Z[LTH[PJ (\LY + / NLSZJOpќLY :+ -PZJOLY () Rudel T (2019) Helaine S (2018) Salmonella persisters undermine host Approach To Dissect Virulence Traits in Candida albicans. The chlamydial deubiquitinase Cdu1 supports recruitment immune defenses during antibiotic treatment. Science Börtlein C, Draeger A, Schoenauer R, Kuhlemann A, Sauer mSphere 4(3):e00258-19 of Golgi vesicles to the inclusion. Cellular Microbiology 362(6419):1156-1160 M, Schneider-Schaulies S, Avota E (2018) The Neutral 22(5):e13136 :WOPUNVT`LSPUHZL0Z9LX\PYLK[V7VSHYPaLHUK:\Z[HPU; Pérez JC (2019) Candida albicans dwelling in the Vendelova E, Ashour D, Blank P, Erhard F, Saliba AE, Cell Receptor Signaling. Frontiers in Immunology 9:815 mammalian gut. Current Opinion in Microbiology Eisenreich W, Rudel T, Heesemann J, Goebel W Kalinke U, Lutz MB (2018) Tolerogenic Transcriptional 52:41-46 (2019) How Viral and Intracellular Bacterial Pathogens Signatures of Steady-State and Pathogen-Induced Collenburg L, Schneider-Schaulies S, Avota E (2018) Reprogram the Metabolism of Host Cells to Allow Their Dendritic Cells. Frontiers in Immunology 9:333 The neutral sphingomyelinase 2 in T cell receptor signaling Intracellular Replication. Front Cell Infect Microbiol 9:42 and polarity. 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Frontiers in Cell and Developmental Microbiology 20(10):e12940 Gulve N, Prusty BK, Rudel T (2019) Chlamydia trachomatis PU 4V\ZL ([OLYVZJSLYVZPZ +LÄULK I` :PUNSL*LSS 95( Biology 7:152 impairs host base excision repair by downregulating Sequencing and Mass Cytometry. Circulation Research Fischer A, Rudel T (2018) Subversion of Cell-Autonomous WVS`TLYHZLуCellular Microbiology 21(4):e12986 122(12):1675-1688 Derakhshani S, Kurz A, Japtok L, Schumacher F, Pilgram Host Defense by Chlamydia Infection. 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Schoenauer R, Larpin Y, Babiychuk EB, Drücker P, Peters S, Schlegel J, Becam J, Avota E, Sauer M, Merz V, Lenhart J, Vonhausen Y, Ortiz-Soto ME, Seibel Smyth RP, Negroni M, Lever AM, Mak J, Kenyon JC Babiychuk VS, Avota E, Schneider-Schaulies S, Schubert-Unkmeir A (2019) Neisseria meningitidis Type J, Krueger A (2019) A^P[[LYPVU-\UJ[PVUHSPaLK+L[VUH[PVU (2018) RNA Structure-A Neglected Puppet Master for :JO\THJOLY - 2SL\ZLY ) 2€ќLS 9 +YHLNLY (   0=7PSP;YPNNLY*H+LWLUKLU[3`ZVZVTHS;YHѝJRPUNVM Nanodiamond with Superior Protein Repulsion and the Evolution of Virus and Host Immunity. Frontiers in Down-regulation of acid sphingomyelinase and neutral the Acid Sphingomyelinase To Enhance Surface Ceramide Colloidal Stability in Physiological Media. Small Immunology 9:2097 sphingomyelinase-2 inversely determines the cellular Levels. Infection and Immunity 87(8):e00410-19 15(48):e1901551 resistance to plasmalemmal injury by pore-forming toxins. Smyth RP, Smith MR, Jousset AC, Despons L, Laumond Federation of American Societies for Experimental Schlegel J, Peters S, Doose S, Schubert-Unkmeir A, Ortiz-Soto ME, Porras-Domínguez JR, Seibel J, López- G, Decoville T, Cattenoz P, Moog C, Jossinet F, Mougel Biology Journal 33(1):275-285 Sauer M (2019) Super-Resolution Microscopy Reveals Munguía A (2019) A close look at the structural features M, Paillart JC, von Kleist M, Marquet R (2018) In cell Local Accumulation of Plasma Membrane Gangliosides and reaction conditions that modulate the synthesis of mutational interference mapping experiment (in cell MIME) at Neisseria meningitidis Invasion Sites. Frontiers in Cell low and high molecular weight fructans by levansucrases. PKLU[PÄLZ[OLºWVS`HKLU`SH[PVUZPNUHSHZHK\HSYLN\SH[VY and Developmental Biology 7:194 Carbohydrate Polymers 219:130-142 of HIV-1 genomic RNA production and packaging. SCHOEN, CHRISTOPH Nucleic Acids Research 46(9):e57 Ortiz-Soto ME, Reising S, Schlosser A, Seibel J (2019) Heidrich N, Bauriedl S, Schoen C (2019) Investigating Structural and functional role of disulphide bonds Mailler E, Paillart JC, Marquet R, Smyth RP, Vivet- RNA-Protein Interactions in Neisseria meningitidis by RIP- SEIBEL, JÜRGEN and substrate binding residues of the human beta- Boudou V (2019) The evolution of RNA structural probing Seq Analysis. Methods Mol Biol 1969:33-49 galactoside alpha-2,3-sialyltransferase 1 (hST3Gal1). methods: From gels to next-generation sequencing. Fink J, Seibel J (2018) Click reactions with functional 6FLHQWLðF5HSRUWV 9(1):17993 WIREs RNA 10(2):e1518 Heidrich N, Hagmann A, Bauriedl S, Vogel J, Schoen C sphingolipids. Biological Chemistry 399(10):1157- (2019) The CRISPR/Cas system in Neisseria meningitidis 1168 Possiel C, Ortiz-Soto ME, Ertl J, Münch A, Vogel A, HќLJ[Z IHJ[LYPHS HKOLZPVU [V O\THU UHZVWOHY`UNLHS Schmiedel R, Seibel J (2019) Exploring the sequence epithelial cells. RNA Biology 16(4):390-396 Gutmann M, Braun A, Seibel J, Lühmann T (2018) ]HYPHIPSP[` VM WVS`TLYPaH[PVUPU]VS]LK YLZPK\LZ PU [OL STICH, AUGUST )PVVY[OVNVUHS TVKPÄJH[PVU VM JLSS KLYP]LK TH[YPJLZ I` production of levan- and inulin-type fructooligosaccharides Liese JG, Schoen C, van der Linden M, Lehmann L, metabolic glyco-engineering. ACS Biomaterials Science with a levansucrase. 6FLHQWLðF5HSRUWV9(1):7720 Gertler M, Loik S, Kleine C, Matuschek A, Gresser N, Goettler D, Keller S, Maier A, Segerer F, Rose MA, Streng & Engineering 4(4):1300-1306 di Gennaro M, Fabricius A, Kratz T, Stich A, Butenop A (2019) Changes in the incidence and bacterial aetiology J (2018) West Africa Ebola outbreak - immediate and VMWHLKPH[YPJWHYHWUL\TVUPJWSL\YHSLќ\ZPVUZLTW`LTH Kaiser D, Winne JM, Ortiz-Soto ME, Seibel J, Le hands-on formation: the pre-deployment training in Germany, 2010-2017: a nationwide surveillance study. TA, Engels B (2018) Mechanistical Insights into the SHARMA, CYNTHIA program for frontline aid workers of the German Clinical Microbiology and Infection 25(7):857-864 )PVJVUQ\NH[PVU9LHJ[PVUVM;YPHaVSPULKPVULZ^P[O;`YVZPUL 9LK *YVZZ V[OLY HPK VYNHUPaH[PVUZ HUK [OL .LYTHU Journal of Organic Chemistry 83(17):10248-10260 Dugar G, Leenay RT, Eisenbart SK, Bischler T, Aul BU, (YTLK -VYJLZ >\LYaI\YN .LYTHU`  Beisel CL, Sharma CM (2018) CRISPR RNA-Dependent Bundesgesundheitsblatt – Gesundheitsforschung – Kraus M, Grimm C, Seibel J (2018) Reversibility of a Binding and Cleavage of Endogenous RNAs by the Gesundheitsschutz 61(4):394-403 SCHUBERT-UNKMEIR, ALEXANDRA Point Mutation Induced Domain Shift: Expanding the Campylobacter jejuni Cas9. Molecular Cell 69(5):893- Conformational Space of a Sucrose Phosphorylase. 905.e7 Giroud M, Dietzel U, Anselm L, Banner D, Kuglstatter A, Herrmann JB, Muenstermann M, Strobel L, Schubert- 6FLHQWLðF5HSRUWV 8(1):10490 Benz J, Blanc JB, Gaufreteau D, Liu H, Lin X, Stich A, Unkmeir A >VVKY\ќ ;4 .YH`6^LU :+ 2SVZ ( Fei J, Sharma CM (2018) 95(3VJHSPaH[PVUPU)HJ[LYPH Kuhn B, Schuler F, Kaiser M, Brun R, Schirmeister T, Kisker Johswich KO (2018) Complement C5a Receptor 1 Ortiz-Soto ME, Ertl J, Mut J, Adelmann J, Le TA, Shan Microbiology Spectrum 6(5) C, Diederich F, Haap W (2018) Repurposing a Library of Exacerbates the Pathophysiology of N. meningitidis J, Teßmar J, Schlosser A, Engels B, Seibel J (2018) /\THU*H[OLWZPU33PNHUKZ!0KLU[PÄJH[PVUVM4HJYVJ`JSPJ Sepsis and Is a Potential Target for Disease Treatment. 7YVK\J[VYPLU[LK JOLTPJHS Z\YMHJL TVKPÄJH[PVU VM H Lerch MF, Schoenfelder SMK, Marincola G, Wencker Lactams as Potent Rhodesain and Trypanosoma brucei mBio 9(1):e01755-17 levansucrase (SacB) via an ene-type reaction. Chemical FDR, Eckart M, Förstner KU, Sharma CM, Thormann Inhibitors. J Med Chem 61(8):3350-3369 Science 9(24):5312-5321 KM, Kucklick M, Engelmann S, Ziebuhr W (2019) A non- Krüger S, Eichler E, Strobel L, Schubert-Unkmeir A, coding RNA from the intercellular adhesion (ica) locus Johswich KO (2018) +PќLYLU[PHSPUÅ\LUJLZVMJVTWSLTLU[ Beliu G, Kurz AJ, Kuhlemann AC, Behringer-Pliess of Staphylococcus epidermidis controls polysaccharide on neutrophil responses to Neisseria meningitidis L, Meub M, Wolf N, Seibel J, Shi ZD, Schnermann PU[LYJLSS\SHY HKOLZPVU 70(TLKPH[LK IPVÄST MVYTH[PVU VAETH, MARTIN infection. Pathogens and Disease 76(8) M, Grimm JB, Lavis LD, Doose S, Sauer M (2019) Molecular Microbiology 111(6):1571-1591 )PVVY[OVNVUHS SHILSPUN ^P[O [L[YHaPULK`LZ MVY Z\WLY Chen X, Kozhaya L, Tastan C, Placek L, Dogan M, Horne Simonis A, Schubert-Unkmeir A (2018) The role of resolution microscopy. Communications Biology 2:261 Schoenfelder SMK, Lange C, Prakash SA, Marincola M, Abblett R, Karhan E, Vaeth M, Feske S, Unutmaz D acid sphingomyelinase and modulation of sphingolipid G, Lerch MF, Wencker FDR, Förstner KU, Sharma (2018) Functional Interrogation of Primary Human T Cells metabolism in bacterial infection. Biological Chemistry Ertl J, Ortiz-Soto ME, Le TA, Bechold J, Shan J, Teßmar J, CM, Ziebuhr W (2019) The small non-coding RNA via CRISPR Genetic Editing. The Journal of Immunology 399(10):1135-1146 Engels B, Seibel J (2019) Tuning the Product Spectrum of 9ZH, PUÅ\LUJLZ L_[YHJLSS\SHY TH[YP_ JVTWVZP[PVU PU 201(5):1586-1598 H.S`JVZPKL/`KYVSHZL,Ua`TLI`H*VTIPUH[PVUVM:P[L :[HWO`SVJVJJ\ZLWPKLYTPKPZIPVÄSTJVTT\UP[PLZ PLoS Kim BJ, McDonagh MA, Deng L, Gastfriend BD, +PYLJ[LK 4\[HNLULZPZ HUK ;`YVZPUL:WLJPÄJ *OLTPJHS Pathogens 15(3):e1007618 Diercks BP, Werner R, Weidemüller P, Czarniak F, Schubert-Unkmeir A, Doran KS, Shusta EV (2019) 4VKPÄJH[PVU Chemistry 25(26):6533-6541 Hernandez L, Lehmann C, Rosche A, Krüger A, Kaufmann Streptococcus agalactiae disrupts P-glycoprotein function Korkut DN, Alves ID, Vogel A, Chabas S, Sharma CM, U, Vaeth M, Failla AV, Zobiak B, Kandil FI, Schetelig D, in brain endothelial cells. Fluids Barriers CNS 16(1):26 Gutmann M, Bechold J, Seibel J, Meinel L, Lühmann T Martinez D, Loquet A, Salgado GF, Darfeuille F (2020) Ruthenbeck A, Meier C, Lodygin D, Flügel A, Ren D, Wolf (2019) Metabolic glycoengineering of cell derived matrices Structural insights into the AapA1 toxin of Helicobacter IMA, Feske S, Guse AH (2018) ORAI1, STIM1/2, and Kim BJ, Schubert-Unkmeir A (2019) In Vitro Models for and cell surfaces – a combination of key principles and pylori. Biochimica et Biophysica Acta General RYR1 shape subsecond Ca2+ microdomains upon T cell Studying the Interaction of Neisseria meningitidis with step-to-step procedures ACS Biomaterials Science & Subjects 1864(1):129423 (Epub 2019) activation. Science Signaling 11(561):eaat0358 Human Brain Endothelial Cells. Methods in Molecular Engineering 5(1):215–233 Biology 1969:135-148 Lian J, Cuk M, Kahlfuss S, Kozhaya L, Vaeth M, Rieux- Irsheid L, Wehler T, Borek C, Kiefer W, Brenk R, Ortiz- Laucat F, Picard C, Benson MJ, Jakovcevic A, Bilic Martins Gomes SF, Westermann AJ, Sauerwein T, Hertlein Soto ME, Seibel J, Schirmeister T (2019) 0KLU[PÄJH[PVU SMYTH, REDMOND K, Martinac I, Stathopulos P, Kacskovics I, Vraetz T, T, Förstner KU, Ohlsen K, Metzger M, Shusta EV, Kim BJ, VM H WV[LU[PHS HSSVZ[LYPJ ZP[L VM .VSNP тTHUUVZPKHZL Speckmann C, Ehl S, Issekutz T, Unutmaz D, Feske Appelt-Menzel A, Schubert-Unkmeir A (2019) Induced II using computer-aided drug design. PLoS ONE Ferhadian D, Contrant M, Printz-Schweigert A, Smyth S (2018) ORAI1 mutations abolishing store-operated Pluripotent Stem Cell-Derived Brain Endothelial Cells as 14(5):e0216132 RP, Paillart JC, Marquet R (2018) Structural and Ca2+ entry cause anhidrotic ectodermal dysplasia with a Cellular Model to Study Neisseria meningitidis Infection. -\UJ[PVUHS 4V[PMZ PU 0UÅ\LUaH =PY\Z 95(Z Frontiers in PTT\UVKLÄJPLUJ` Journal of Allergy and Clinical Frontiers in Microbiology 10:1181 Immunology 9:559 Immunology 142(4):1297-1310.e11

166 167 7.5 PUBLICATIONS

Saint Fleur-Lominy S, Maus M, Vaeth M, Lange I, Zee I, Westermann AJ, Vogel J (2018) Host-pathogen Moremi N, Claus H, Rutta L, Frosch M, Vogel U, Mshana Stapels DAC, Hill PWS, Westermann AJ, Fisher Suh D, Liu C, Wu X, Tikhonova A, Aifantis I, Feske S (2018) transcriptomics by Dual RNA-seq. Methods in Molecular SE (2018) High carriage rate of extended-spectrum beta- RA, Thurston TL, Saliba AE, Blommestein I, Vogel J, :;04HUK:;044LKPH[L*HUJLY0UK\JLK0UÅHTTH[PVU Biology 1737:59-75 lactamase-producing Enterobacteriaceae among patients Helaine S (2018) Salmonella persisters undermine host in T Cell Acute Lymphoblastic Leukemia. Cell Reports HKTP[[LKMVYZ\YNLY`PU;HUaHUPHUOVZWP[HSZ^P[OHSV^YH[L immune defenses during antibiotic treatment. Science 24(11):3045-3060.e5 Yu SH, Vogel J, Förstner KU (2018) ANNOgesic: a Swiss of endogenous surgical site infections. The Journal of 362(6419):1156-1160 army knife for the RNA-seq based annotation of bacterial/ Hospital Infection 100(1):47-53 Vaeth M, Feske S (2018) Ion channelopathies of the archaeal genomes. GigaScience 7(9):giy096 Westermann AJ (2018) Regulatory RNAs in Virulence immune system. Curr Opin Immunol 52:39-50 Alashkar F, Vance C, Herich-Terhürne D, Turki AT, Schmitz and Host-Microbe Interactions. Microbiology Spectrum Chihara K, Bischler T, Barquist L, Monzon VA, Noda N, C, Bommer M, Hüttmann A, Dührsen U, Vogel U, Röth A 6(4):305-337 Vaeth M, Feske S (2018) NFAT control of immune function: Vogel J, Tsuneda S (2019) Conditional Hfq Association (2019) Serologic response to meningococcal vaccination New Frontiers for an Abiding Trooper. F1000Res 7:260 with Small Noncoding RNAs in Pseudomonas aeruginosa in patients with cold agglutinin disease (CAD) in the novel Westermann AJ, Vogel J (2018) Host-Pathogen Revealed through Comparative UV Cross-Linking era of complement inhibition. Vaccine 37(44):6682-6687 Transcriptomics by Dual RNA-Seq. Methods in Eckstein M, Vaeth M, Aulestia FJ, Costiniti V, Kassam SN, Immunoprecipitation Followed by High-Throughput Molecular Biology 1737:59-75 Bromage TG, Pedersen P, Issekutz T, Idaghdour Y, Moursi Sequencing. mSystems 4(6):e00590-19 Claus H, Hubert K, Becher D, Otto A, Pawlik MC, AM, Feske S, Lacruz RS (2019) +PќLYLU[PHS YLN\SH[PVU Lappann I, Strobel L, Vogel U, Johswich K (2019) A Martins Gomes SF, Westermann AJ, Sauerwein T, of Ca2+ PUÅ\_ I` 69(0 JOHUULSZ TLKPH[LZ LUHTLS Gerovac M, Vogel J (2019) An RNA Surprise in Bacterial homopolymeric adenosine tract in the promoter region of Hertlein T, Förstner KU, Ohlsen K, Metzger M, Shusta EV, TPULYHSPaH[PVU Science Signaling 12(578):eaav4663 ,ќLJ[VY4LJOHUPZTZ. Cell Host & Microbe 26(6):709-711 UZW( PUÅ\LUJLZ MHJ[VY /TLKPH[LK ZLY\T YLZPZ[HUJL PU Kim BJ, Appelt-Menzel A, Schubert-Unkmeir A (2019) Neisseria meningitidis. 6FLHQWLðF5HSRUWV 9(1):2736 Induced Pluripotent Stem Cell-Derived Brain Endothelial Vaeth M, Wang YH, Eckstein M, Yang J, Silverman GJ, Heidrich N, Hagmann A, Bauriedl S, Vogel J, Schoen C Cells as a Cellular Model to Study Neisseria meningitidis Lacruz RS, Kannan K, Feske S (2019) Tissue resident (2019) The CRISPR/Cas system in Neisseria meningitidis Drayß M, Claus H, Hubert K, Thiel K, Berger A, Sing Infection. Frontiers in Microbiology 10:1181 HUKMVSSPJ\SHY;YLNJLSSKPќLYLU[PH[PVUPZYLN\SH[LKI`*9(* HќLJ[Z IHJ[LYPHS HKOLZPVU [V O\THU UHZVWOHY`UNLHS A, Linden MV, Vogel U, Lâm TT (2019) Asymptomatic channels. Nature Communications 10(1):1183 epithelial cells. RNA Biology 16(4):390-396 JHYYPHNLVM5LPZZLYPHTLUPUNP[PKPZ/HLTVWOPS\ZPUÅ\LUaHL Westermann AJ, Venturini E, Sellin M, Förstner K, Hardt Streptococcus pneumoniae, Group A Streptococcus and W, Vogel J (2019) The Major RNA-Binding Protein ProQ Miyakoshi M, Matera G, Maki K, Sone Y, Vogel J (2019) Staphylococcus aureus among adults aged 65 years and Impacts Virulence Gene Expression in Salmonella enterica Functional expansion of a TCA cycle operon mRNA by older. PLoS ONE 14(2):e0212052 Serovar Typhimurium. mBio 10(1):e02504-18 VOGEL, JÖRG a 3‘ end-derived small RNA. Nucleic Acids Research 47(4):2075-2088 2YVUL 4 .YH` : (IHK 9 :RVJa`ljZRH ( :[LMHULSSP 7 El Mouali Y, Gaviria-Cantin T, Sánchez-Romero MA, et al.2̿xüV]m7,TVUL[:*H\NHU[+(;VYVWHPULU4 Gibert M, Westermann AJ, Vogel J, Balsalobre C Westermann AJ, Venturini E, Sellin ME, Förstner KU, =HaX\La1>HNjRV02UVS411HJVIZZVU:9VKYPN\LZ ZIEBUHR, WILMA (2018) CRP-cAMP mediates silencing of Salmonella Hardt WD, Vogel J (2019) The Major RNA-Binding Protein Bettencourt C, Musilek M, Born R, Vogel U, Borrow R virulence at the post-transcriptional level. PLoS Genetics ProQ Impacts Virulence Gene Expression in Salmonella (2019) Increase of invasive meningococcal serogroup Balasubramanian S, Skaf J, Holzgrabe U, Bharti R, 14(6):e1007401 enterica Serovar Typhimurium. mBio 10(1):02504-18 W disease in Europe, 2013 to 2017. Eurosurveillance Förstner KU, Ziebuhr W, Humeida UH, Abdelmohsen 24(14):1800245 UR, Oelschlaeger TA (2018) A New Bioactive Compound Holmqvist E, Vogel J (2018) RNA-binding proteins in From the Marine Sponge-Derived Streptomyces sp. bacteria. Nature Reviews Microbiology 16(10):601-615 Moremi N, Claus H, Silago V, Kabage P, Abednego R, :);  0UOPIP[Z :[HWO`SVJVJJHS .YV^[O HUK )PVÄST VOGEL, ULRICH Matee M, Vogel U, Mshana SE (2019) Hospital surface Formation. Frontiers in Microbiology 9:1473 Holmqvist E, Li L, Bischler T, Barquist L, Vogel J (2018) contamination with antimicrobial-resistant Gram-negative Global maps of ProQ binding in vivo reveal target Hagemeister MH, Stock NK, Ludwig T, Heuschmann VYNHUPZTZPU;HUaHUPHUYLNPVUHSHUK[LY[PHY`OVZWP[HSZ![OL Heilmann C, Ziebuhr W, Becker K (2019) Are coagulase- recognition via RNA structure and stability control at P, Vogel U (2018) :LSMYLWVY[LK PUÅ\LUaH ]HJJPUH[PVU need to improve environmental cleaning. The Journal of negative staphylococci virulent? Clinical Microbiology mRNA 3‘ ends. Molecular Cell 70(5):971-982.e6 rates and attitudes towards vaccination among health Hospital Infection 102(1):98-100 and Infection 25(9):1071-1080 care workers: results of a survey in a German university Hör J, Gorski SA, Vogel J (2018) Bacterial RNA Biology hospital. Public Health 154:102-109 Moremi N, Claus H, Vogel U, Mshana SE (2019) The role Lerch MF, Schoenfelder SMK, Marincola G, Wencker on a Genome Scale. Molecular Cell 70(5):785-799 of patients and healthcare workers Staphylococcus aureus FDR, Eckart M, Förstner KU, Sharma CM, Thormann Jockel-Schneider Y, Kobsar A, Stellzig-Eisenhauer A, UHZHSJVSVUPaH[PVUPUVJJ\YYLUJLVMZ\YNPJHSZP[LPUMLJ[PVU KM, Kucklick M, Engelmann S, Ziebuhr W (2019) A non- Munschauer M, Vogel J (2018) Nuclear lncRNA Vogel U, Störk S, Frantz S, Schlagenhauf U, Eigenthaler HTVUN WH[PLU[Z HKTP[[LK PU [^V JLU[LYZ PU ;HUaHUPH coding RNA from the intercellular adhesion (ica) locus Z[HIPSPaH[PVU PU [OL OVZ[ YLZWVUZL [V IHJ[LYPHS PUMLJ[PVU M (2018) Wild-type isolates of Porphyromonas gingivalis Antimicrobial Resistance and Infection Control 8:102 of Staphylococcus epidermidis controls polysaccharide The EMBO Journal 37(13):e99875 derived from periodontitis patients display major variability PU[LYJLSS\SHY HKOLZPVU 70(TLKPH[LK IPVÄST MVYTH[PVU in platelet activation. Journal of Clinical Periodontology Molecular Microbiology 111(6):1571-1591 Müller LSM, Cosentino RO, Förstner KU, Guizetti J, 45(6):693-700 Wedel C, Kaplan N, Janzen CJ, Arampatzi P, Vogel J, WESTERMANN, ALEXANDER Marincola G, Wencker FDR, Ziebuhr W (2019) The Many Steinbiss S, Otto TD, Saliba AE, Sebra RP, Siegel TN Karrasch M, Eisenach S, Vogel U, Zinke J, Witte OW, Facets of the Small Non-coding RNA RsaE (RoxS) in (2018) .LUVTL VYNHUPaH[PVU HUK +5( HJJLZZPIPSP[` Günther A, Romeike B, Rödel J (2018) Value of the El Mouali Y, Gaviria-Cantin T, Sánchez-Romero MA, Metabolic Niche Adaptation of Gram-Positive Bacteria. control antigenic variation in trypanosomes. Nature LHa`WSL_Ž *:- KPYLJ[ HZZH` PU YHWPK KPHNUVZPZ VM Gibert M, Westermann AJ, Vogel J, Balsalobre C Journal of Molecular Biology 431(23):4684-4698 563(7729):121-125 invasive meningococcal disease - Case report. Acta (2018) CRP-cAMP mediates silencing of Salmonella Microbiologica et Immunologica Hungarica 65(3):309- virulence at the post-transcriptional level. PLoS Genetics Schoenfelder SMK, Lange C, Prakash SA, Marincola Stapels DAC, Hill PWS, Westermann AJ, Fisher RA, 315 14(6):e1007401 G, Lerch MF, Wencker FDR, Förstner KU, Sharma Thurston TL, Saliba AE, Blommestein I, Vogel J, CM, Ziebuhr W (2019) The small non-coding RNA Helaine S (2018) Salmonella persisters undermine host McNeil LK, Donald RGK, Gribenko A, French R, Lambert Frönicke L, Bronner DN, Byndloss MX, McLaughlin B, 9ZH, PUÅ\LUJLZ L_[YHJLSS\SHY TH[YP_ JVTWVZP[PVU PU immune defenses during antibiotic treatment. Science N, Harris SL, Jones TR, Li S, Zlotnick G, Vogel U, Claus Bäumler AJ, Westermann AJ (2018) Toward Cell Type- :[HWO`SVJVJJ\ZLWPKLYTPKPZIPVÄSTJVTT\UP[PLZ PLoS 362(6419):1156-1160 H, Abad R, Vazquez JA, Borrow R, Findlow J, Taha MK, :WLJPÄJ0U=P]V+\HS95(:LXMethods in Enzymology Pathogens 15(3):e1007618 Deghmane AE, Caugant DA, Kriz P, Musilek M, Wang X, 612:505-522 Tawk C, Nigro G, Rodrigues Lopes I, Aguilar C, Lisowski Vuong J, Mayer LW, Pride MW, Jansen KU, Anderson C, Mano M, Sansonetti P, Vogel J, Eulalio A (2018) AS (2018) Predicting the Susceptibility of Meningococcal Simon LM, Karg S, Westermann AJ, Engel M, Elbehery Stress-induced host membrane remodeling protects from Serogroup B Isolates to Bactericidal Antibodies Elicited AHA, Hense B, Heinig M, Deng L, Theis FJ (2018) infection by non-motile bacterial pathogens. The EMBO by Bivalent rLP2086, a Novel Prophylactic Vaccine. MetaMap: an atlas of metatranscriptomic reads in human Journal 37(23):e98529 mBio 9(2):e00036-18 disease-related RNA-seq data. GigaScience 7(6):giy070

168 169 7.6 DIRECTORY OF PEOPLE ASSOCIATED WITH THE ZINF

7.6 DIRECTORY OF YOUNG INVESTIGATORS

PEOPLE ASSOCIATED WITH THE ZINF DR. SINA BARTFELD DR. SEBASTIAN GEIBEL ZINF (since 2015) ,SP[L5L[a^LYR)H`LYUZPUJL Zentrum für Infektionsforschung (ZINF) Institut für Molekulare Infektionsbiologie (IMIB) Josef-Schneider-Str. 2 / D15 Josef-Schneider-Str. 2 / D15 D-97080 Würzburg D-97080 Würzburg T +49 931 31 80121 T +49 931 31 84590 EXECUTIVE COMMITTEE MEMBERS M [email protected] M [email protected]

PROF. DR. CYNTHIA SHARMA PROF. DR. OLIVER KURZAI DR. ANA RITA BROCHADO DR. J. CHRISTIAN PÉREZ Spokesperson of the ZINF (since 2018) Institut für Hygiene und Mikrobiologie ZINF/Biocenter (since 2019) ZINF/IZKF (since 2014) Institut für Molekulare Infektionsbiologie (IMIB) Lehrstuhl für Medizinische Mikrobiologie und Mykologie Biozentrum Zentrum für Infektionsforschung (ZINF) Lehrstuhl für Molekulare Infektionsbiologie II Josef-Schneider-Str. 2 / E1 Lehrstuhl für Mikrobiologie Josef-Schneider-Str. 2 / D15 Josef-Schneider-Str. 2 / D15 D-97080 Würzburg Am Hubland D-97080 Würzburg D-97080 Würzburg T +49 931 31 88007 D-97074 Würzburg T +49 931 31 83815 T +49 931 31 82560 M [email protected] T +49 931 31 88860 M [email protected] M [email protected] M [email protected]

PROF. DR. THOMAS RUDEL PROF. DR. LARS DÖLKEN Biozentrum DR. FRANZISKA FABER Institut für Virologie und Immunbiologie Lehrstuhl für Mikrobiologie ZINF (since 2018) Lehrstuhl für Virologie Am Hubland Zentrum für Infektionsforschung (ZINF) Versbacher Str. 7 / E5 D-97074 Würzburg Josef-Schneider-Str. 2 / D15 D-97078 Würzburg T +49 931 31 84401 D-97080 Würzburg T +49 931 31 88185 M [email protected] T +49 931 31 86280 M [email protected] M [email protected]

PROF. DR. JÖRG VOGEL PROF. DR. HERMANN EINSELE Spokesperson of the ZINF (2011-2017) Medizinische Klinik und Poliklinik II Institut für Molekulare Infektionsbiologie (IMIB) Zentrum Innere Medizin (ZIM) Lehrstuhl für Molekulare Infektionsbiologie I Oberdürrbacher Straße 6 / A3 Helmholtz-Institut für RNA-basierte MEMBERS D-97080 Würzburg Infektionsforschung (HIRI) T +49 931 201 40001 Josef-Schneider-Str. 2 / D15 M [email protected] D-97080 Würzburg JUN. PROF. DR. LARS BARQUIST PD DR. NIKLAS BEYERSDORFER T +49 931 31 82576 Helmholtz-Institut für RNA-basierte Institut für Virologie und Immunbiologie M [email protected] Infektionsforschung (HIRI) Versbacher Str. 7 / E5 PROF. DR. MATTHIAS FROSCH Josef-Schneider-Str. 2 / D15 D-97078 Würzburg Spokesperson of the ZINF (2008-2011) D-97080 Würzburg T +49 931 31 81527 Institut für Hygiene und Mikrobiologie T +49 931 31 82513 M [email protected] Lehrstuhl für Hygiene und Mikrobiologie M [email protected] Josef-Schneider-Str. 2 / E1 D-97080 Würzburg PROF. DR. KLAUS BREHM T +49 931 31 46160 PROF. DR. DR. ANDREAS BEILHACK Institut für Hygiene und Mikrobiologie M [email protected] Medizinische Klinik und Poliklinik II Josef-Schneider-Str. 2 / E1 Zentrum für Experimentelle Molekulare Medizin (ZEMM) D-97080 Würzburg Zinklesweg 10 T +49 931 31 46168 PROF. DR. WOLFGANG KASTENMÜLLER D-97080 Würzburg M [email protected] Institut für Systemimmunologie T +49 (0)931-20144040 Lehrstuhl für Systemimmunologie I M [email protected] Versbacher Str. 9/E6 JUN. PROF. DR. NEVA CALISKAN D-97078 Würzburg Helmholtz-Institut für RNA-basierte T +49 931 31 81816 PROF. DR. CHASE BEISEL Infektionsforschung (HIRI) M [email protected] Helmholtz-Institut für RNA-basierte Josef-Schneider-Str. 2 / D15 Infektionsforschung (HIRI) D-97080 Würzburg Josef-Schneider-Str. 2 / D15 T +49 931 31 85298 D-97078 Würzburg M [email protected] T +49 931 31 85346 M [email protected]

170 171 7.6 DIRECTORY OF PEOPLE ASSOCIATED WITH THE ZINF

MEMBERS

PROF. DR. THOMAS DANDEKAR PROF. DR. THOMAS HERRMANN PD DR. MARCO METZGER PROF. DR. SIBYLLE SCHNEIDER-SCHAULIES Biozentrum Institut für Virologie und Immunbiologie Lehrstuhl für Tissue Engineering und Regenerative Institut für Virologie und Immunbiologie Lehrstuhl für Bioinformatik Versbacher Str. 7 / E5 Medizin (TERM) Versbacher Str. 7 / E5 Am Hubland D-97078 Würzburg Röntgenring 11 D-97078 Würzburg D-97074 Würzburg T +49 931 31 81538 D-97070 Würzburg T +49 931 31 81566 T +49 931 31 84551 M [email protected] T +49 931 31 86686 M [email protected] M [email protected] M [email protected]

PROF. DR. ULRIKE HOLZGRABE PROF. DR. DR. CHRISTOPH SCHOEN PROF. DR. MARKUS ENGSTLER Institut für Pharmazie und Lebensmittelchemie PROF. DR. HEIDRUN MOLL Institut für Hygiene und Mikrobiologie Biozentrum Lehrstuhl für Pharmazeutische und Medizinische Chemie Institut für Molekulare Infektionsbiologie (IMIB) Josef-Schneider-Str. 2 / E1 Lehrstuhl für Zell- und Entwicklungsbiologie Am Hubland Josef-Schneider-Str. 2 / D15 D-97080 Würzburg Am Hubland D-97074 Würzburg D-97080 Würzburg T +49 931 31 46162 D-97074 Würzburg T +49 931 31 85461 T +49 931 31 82627 M [email protected] T +49 931 31 80060 M [email protected] M [email protected] M [email protected] PROF. DR. ALEXANDRA SCHUBERT-UNKMEIR PROF. DR. CAROLINE KISKER PROF. DR. JOACHIM MORSCHHÄUSER Institut für Hygiene und Mikrobiologie JUN. PROF. DR. FLORIAN ERHARD Rudolf-Virchow-Zentrum für Experimentelle Institut für Molekulare Infektionsbiologie (IMIB) Josef-Schneider-Str. 2 / E1 Institut für Virologie und Immunbiologie Biomedizin (RVZ) Josef-Schneider-Str. 2 / D15 D-97080 Würzburg Versbacher Str. 7 / E5 Lehrstuhl für Strukturbiologie D-97080 Würzburg T +49 931 31 46721 D-97078 Würzburg Josef-Schneider-Str. 2 / D15 T +49 931 31 82152 M [email protected] T +49 931 31 86523 D-97080 Würzburg M [email protected] M ÅVYPHULYOHYK'\UP^\LYaI\YNKL T +49 931 31 80381 M [email protected] PROF. DR. JÜRGEN SEIBEL DR. MATHIAS MUNSCHAUER Institut für Organische Chemie DR. MARTIN FRAUNHOLZ Helmholtz-Institut für RNA-basierte Am Hubland Biozentrum PROF. DR. HARTWIG KLINKER Infektionsforschung (HIRI) D-97074 Würzburg Lehrstuhl für Mikrobiologie Medizinische Klinik und Poliklinik II Josef-Schneider-Str. 2 / D15 T +49 931 31 85326 Am Hubland Zentrum Innere Medizin (ZIM) D-97080 Würzburg M [email protected] D-97074 Würzburg Oberdürrbacher Straße 6 / A3 T +49 931 31 86951 T +49 931 31 83242 D-97080 Würzburg M [email protected] M [email protected] T +49 931 201 40043 JUN. PROF. DR. REDMOND SMYTH M [email protected] Helmholtz-Institut für RNA-basierte PD DR. KNUT OHLSEN Infektionsforschung (HIRI) PROF. DR. GEORG GASTEIGER Institut für Molekulare Infektionsbiologie (IMIB) Josef-Schneider-Str. 2 / D15 Institut für Systemimmunologie PD DR. VERA KOZJAK-PAVLOVIC Josef-Schneider-Str. 2 / D15 D-97080 Würzburg Lehrstuhl für Systemimmunologie II Biozentrum D-97080 Würzburg T +49 931 31 89152 Versbacher Str. 9 / E6 Lehrstuhl für Mikrobiologie T +49 931 31 82155 M [email protected] D-97078 Würzburg Am Hubland M [email protected] T +49 931 31 89599 D-97074 Würzburg M [email protected] T +49 931 31 88061 PROF. DR. AUGUST STICH M [email protected] DR. ANTOINE-EMMANUEL SALIBA Klinikum Würzburg Mitte gGmbH Helmholtz-Institut für RNA-basierte Standort Missioklinik DR. MERCEDES GOMEZ DE AGÜERO Infektionsforschung (HIRI) Tropenmedizinische Abteilung Institut für Systemimmunologie PROF. DR. JÜRGEN LÖFFLER Josef-Schneider-Str. 2 / D15 Salvatorstr. 7 Versbacher Str. 9 / E6 Medizinische Klinik und Poliklinik II D-97080 Würzburg D-97074 Würzburg D-97078 Würzburg Forschungslabore Haus C11 T +49 931 31 81341 T +49 931 791 2821 T +49 931 31 80303 Josef-Schneider-Str. 2 M [email protected] M [email protected] M [email protected] D-97080 Würzburg T +49 931 201 36412 M SVLўLYFQ'\R^KL PROF. DR. JÜRGEN SCHNEIDER-SCHAULIES DR. MARTIN VAETH PROF. DR. ROY GROSS Institut für Virologie und Immunbiologie Institut für Systemimmunologie Biozentrum Versbacher Str. 7 / E5 Versbacher Str. 9 / E6 Lehrstuhl für Mikrobiologie PROF. DR. MANFRED LUTZ D-97078 Würzburg D-97078 Würzburg Am Hubland Institut für Virologie und Immunbiologie T +49 931 31 81564 T +49 931 31 82491 D-97074 Würzburg Versbacher Str. 7 / E5 M [email protected] M [email protected] T +49 931 31 84403 D-97078 Würzburg M [email protected] T +49 931 31 81553 M [email protected]

172 173 7.6 DIRECTORY OF PEOPLE ASSOCIATED WITH THE ZINF

MEMBERS SCIENTIFIC ADVISORY BOARD MEMBERS

PROF. DR. ULRICH VOGEL PROF. DR. MICHAEL GILMORE PROF. DR. DAVID HOLDEN Institut für Hygiene und Mikrobiologie Chair of the SAB (since 2013) (since 2013) Josef-Schneider-Str. 2 / E1 Harvard Medical School Imperial College London D-97080 Würzburg Department of Ophthalmology Centre for Molecular Bacteriology and Infection T +49 931 31 46802 Microbiology and Immunobiology Flowers Building, Exibition Road M [email protected] 243 Charles St. London SW7 2AZ Boston, MA 02114 United Kingdom USA T +44 20 7594 3073 JUN. PROF. DR. ALEXANDER WESTERMANN T +1 617 573 3845 M [email protected] Institut für Molekulare Infektionsbiologie (IMIB) M [email protected] Josef-Schneider-Str. 2 / D15 D-97080 Würzburg PROF. DR. ERIC PAMER T +49 931 31 83781 PROF. DR. KATJA BECKER (since 2016) M [email protected] (2016 - 2019) University of Chicago Justus-Liebig Universität Giessen Duchossois Family Institute Interdisziplinäres Forschungszentrum 900 E. 57th St., KCBD 4140 PD DR. WILMA ZIEBUHR Lehrstuhl für Biochemie und Molekularbiologie Chicago, IL 60637 Institut für Molekulare Infektionsbiologie (IMIB) /LPUYPJO)\ќ9PUN USA Josef-Schneider-Str. 2 / D15 D-35392 Giessen T +1 773 834 6015 D-97080 Würzburg T +49 641 99 39120 M [email protected] T +49 931 31 82154 M [email protected] M [email protected] since 2020: DR. GISELA STORZ Präsidentin der (since 2013) Deutschen Forschungsgemeinschaft (DFG) National Institute of Child Health and Human Kennedyallee 40 Development D-53175 Bonn Division of Molecular and Cellular Biology T +49 228 885 2222 49 Convent Drive M [email protected] Bethesda, MD 20892-4417 USA T +1 301 402 0968 PROF. DR. MELANIE BLOKESCH M [email protected] (since 2019) Swiss Federal Institute of Technology Lausanne (EPFL) PROF. DR. TONE TØNJUM EPFL SV GHI UPBLO (since 2013) Station 19 Oslo University Hospital 1015 Lausanne Institute of Microbiology Switzerland Unit for Genome Dynamics T +41 21 693 0653 Pb. 4950 Nydalen M TLSHUPLISVRLZJO'LWÅJO 0424 Oslo Norway T +47 23074065 PROF. DR. JAY HINTON M [email protected] (since 2019) University of Liverpool Institute of Infection, Veterinary and Ecological Sciences Crown Street Liverpool L69 7ZB United Kingdom T +44 151 795 4573 M [email protected]

174 175 ACKNOWLEDGEMENTS

Thank you very much to Sandy Pernitzsch (SCIGRAPHIX) for the wonderful layout and design of this report! And special thanks to Mona Alzheimer, Hilde Merkert, and 7L[YH ;OVTHZ MVY HSS `V\Y NYLH[ ^VYR QVPU[ LќVY[Z HUK OLSW [V JVTWPSL V\Y    A05- :JPLU[PÄJ 9LWVY[ Moreover, I would like to thank Sarah Svensson for her help with English proofreading.

Cynthia Sharma, November 2020

IMPRESSUM

PUBLISHED BY Research Center for Infectious Diseases Zentrum für Infektionsforschung (ZINF) Josef-Schneider-Str. 2 / D15 D-97080 Würzburg, Germany www.uni-wuerzburg.de/zinf

EDITORIAL TEAM Mona Alzheimer Hilde Merkert Petra Thomas Cynthia Sharma

LAYOUT & DESIGN SCIGRAPHIX Sandy Pernitzsch www.scigraphix.com

PORTRAITS Hilde Merkert

IMAGES If not indicated otherwise in the image or caption, photo- graphs are from Hilde Merkert, IMIB.

ENGLISH PROOFREADING Sarah Svensson

PRINT Schleunungdruck GmbH Marktheidenfeld

NOTICE Neither the research center nor any person acting upon its behalf may be held responsible for the use of information that is contained within this publication, or for any errors that may appear despite careful preparation.

©2020 ZINF

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