Curriculum Vitae

Nicole T. Perna Professor of the Department of Genetics And Genome Center of Wisconsin University of Wisconsin, Madison 425G Henry Mall Madison, WI 53706

Office: (608) 890-0171 Cell: (608) 444-9391 E-mail: [email protected]

Education 1996 Ph.D, Genetics, University of New Hampshire, “Rates and Patterns of Variation Within and Between Animal Mitochondrial Genomes” 1991 B.S., Biology/Genetics, The Pennsylvania State University.

Professional Positions 2013-present Professor, Department of Genetics and Genome Center of Wisconsin 2013-present Director, J.F. Crow Institute for the Study of Evolution 2006-2013 Associate Professor, Genome Center of Wisconsin and Department of Genetics 2009-2011 Founding Director, Advanced Genome Analysis Resource, UW Biotech Center 2000-2006 Assistant Professor, Animal Health and Biomedical Sciences and the Genome Center of Wisconsin, University of Wisconsin-Madison. 1999-2000 Assistant Scientist, Department of Genetics, University of Wisconsin- Madison. 1996-1999 NSF Postdoctoral Fellow (mentor - Dr. Frederick R. Blattner), Department of Genetics, University of Wisconsin-Madison. 1992-1994 Research Assistant (mentor - Dr. Thomas D. Kocher), Program in Genetics, University of New Hampshire. 1991-1995 Teaching Assistant at University of New Hampshire, Introductory Genetics and Biology courses. 1990-1991 Research Technician for Dr. Mark Stoneking, Department of Anthropology, The Pennsylvania State University.

Awards and Fellowships 1996-1998 National Science Foundation-Alfred P. Sloan Foundation Postdoctoral Fellowship in Molecular Evolution

Society Memberships American Society of Microbiologists (ASM) Chair Division R “Evolutionary and Genomic Microbiology”, 2012 Society for Molecular Biology and Evolution Wisconsin Society of Science Teachers

Research Overview Genome evolution is the research focus in my transdisciplinary group. We strive to understand the evolutionary processes that gave rise to bacterial genome architecture, content and expression, and unravel the relationship between genetic variation, fitness and adaptation. Toward this end, we have sequenced, annotated and compared genomes and transcriptomes of diverse enterobacteria leading to key insights into rates and patterns of horizontal gene transfer, evolution of host-microbe interaction factors, and diversity of regulatory and metabolic networks. Along the way, we have developed tools and genome resources widely used by the prokaryotic (and eukaryotic) research communities. We apply our knowledge of variation among species and strains to help improve diagnostic tools for surveillance of both plant and animal pathogens. Ongoing projects include: • Examining the role of regulatory evolution in resolution of functional redundancy introduced by gene duplication and horizontal gene transfers, • Characterizing the evolutionary dynamics of specialization in plant hosts, • Explaining diversity in how facultative anaerobes respond to oxygen availability, • Using machine learning to recognize novel host-microbe interaction genes, and • Reconstructing patterns of gene flow among ancestral lineages.

Select Electronic Resources and Publicly Available Software • Mauve Multiple Genome Alignment and Visualization Tool. This actively maintained software package allows users to align 2 or more complete genome sequences that may include rearrangements or large gaps. Mauve is available (http://gel.ahabs.wisc.edu/mauve/index.php) for Windows, Mac OS X 10.3.9+ (Intel/G4/G5), and Linux, and has been downloaded over 2000 times. Mauve is also available under an open source license for modification and redistribution. • ASAP, A systematic Annotation Package. This MySQL database and PHP interface have been in use for a variety of microbial genome sequencing projects conducted at UW since 2002 (https://asap.ahabs.wisc.edu/asap/logon.php). ASAP provides an environment for storage and distribution of genome sequence data, annotations, comparative genomics and high-throughput experimental data. ASAP also includes functionality for community annotation and curatorial annotation updates. ASAP is available under an open source license for modification and redistribution.

2 Peer Reviewed Publications (66 in total): Burritt NL, Foss NJ, Neeno-Eckwall EC, Church JO, Hilger AM, Hildebrand JA , Warshauer DM, Perna NT, and Burritt JB. Sepsis and immune suppression in honey bees (Apis mellifera) from Serratia marcescens strain sicaria: a new Varroa destructor- borne infection, accepted PLoS ONE. Sapountzis P, Gruntjes T, Otani S, Estevez J, da Costa RR, Plunkett G 3rd, Perna NT, Poulsen M. The Enterobacterium Trabulsiella odontotermitis Presents Novel Adaptations Related to Its Association with Fungus-Growing Termites. Appl Environ Microbiol. 2015 Oct;81(19):6577-88. doi: 10.1128/AEM.01844-15. Epub 2015 Jul 10. PubMed PMID: 26162887; PubMed Central PMCID: PMC4561680. Ma B, Charkowski AO, Glasner JD, Perna NT. Identification of host-microbe interaction factors in the genomes of soft rot-associated pathogens Dickeya dadantii 3937 and Pectobacterium carotovorum WPP14 with supervised machine learning. BMC Genomics. 2014 Jun 21;15:508. doi: 10.1186/1471-2164-15-508. PubMed PMID: 24952641; PubMed Central PMCID: PMC4079955. Byrne RT, Klingele AJ, Wood EA, Cabot EL, Schackwitz W, Martin J, Martin J, Wang Z, Pennacchio C, Pennacchio LA, Perna NT, Battista JR, Cox MM. Evolution of extreme resistance to ionizing radiation via genetic adaptation of DNA repair. 2014. eLife. 2014;3:e01322. DOI: 10.7554/eLife.01322. Chung Y, Perna NT, Ané C. Computing the joint distribution of tree shape and tree distance for gene tree inference and recombination detection. IEEE/ACM Trans Comput Biol Bioinform. 2013 Sep-Oct;10(5):1263-74. doi: 10.1109/TCBB.2013.109. PubMed PMID: 24384712. Babujee L, Balakrishnan V, Kiley PJ, Glasner JD, Perna NT. Transcriptome changes associated with anaerobic growth in Yersinia intermedia (ATCC29909). PLoS One. 2013 Oct 7;8(10):e76567. doi: 10.1371/journal.pone.0076567. eCollection 2013. PubMed PMID: 24116118; PubMed Central PMCID: PMC3792023. Baumler DJ, Ma B, Reed JL, Perna NT. Inferring ancient metabolism using ancestral core metabolic models of enterobacteria. BMC Syst Biol. 2013 Jun 11;7:46. doi: 10.1186/1752-0509-7-46. PubMed PMID: 23758866; PubMed Central PMCID: PMC3694032. Broadbent JR, Neeno-Eckwall EC, Stahl B, Tandee K, Cai H, Morovic W, Horvath P, Heidenreich J, Perna NT, Barrangou R, Steele JL. Analysis of the Lactobacillus casei supragenome and its influence in species evolution and lifestyle adaptation. BMC Genomics. 2012 Oct 5;13(1):533. PMID: 23035691. Charkowski A, Blanco C, Condemine G, Expert D, Franza T, Hayes C, Hugouvieux- Cotte-Pattat N, López Solanilla E, Low D, Moleleki L, Pirhonen M, Pitman A, Perna N, Reverchon S, Rodríguez Palenzuela P, San Francisco M, Toth I, Tsuyumu S, van der Walls J, van der Wolf J, Van Gijsegem F, Yang CH, Yedidia I. The Role of Secretion Systems and Small Molecules in Soft-Rot Enterobacteriaceae Pathogenicity. Annu Rev Phytopathol. 2012 Jun 12. PubMed PMID: 22702350. Babujee L, Apodaca J, Balakrishnan V, Liss P, Kiley PJ, Charkowski AO, Glasner JD, Perna NT. Evolution of the metabolic and regulatory networks associated with oxygen

3 availability in two phytopathogenic enterobacteria. BMC Genomics. 2012 Mar 22;13:110. PubMed PMID: 22439737; PubMed Central PMCID: PMC3349551. Baumler DJ, Banta LM, Hung KF, Schwarz JA, Cabot EL, Glasner JD, Perna NT. Using comparative genomics for inquiry-based learning to dissect virulence of Escherichia coli O157:H7 and Yersinia pestis. CBE Life Sci Educ. 2012 Spring;11(1):81-93. PubMed PMID: 22383620; PubMed Central PMCID: PMC3292067. Rio RV, Symula RE, Wang J, Lohs C, Wu YN, Snyder AK, Bjornson RD, Oshima K, Biehl BS, Perna NT, Hattori M, Aksoy S. Insight into the transmission biology and species-specific functional capabilities of tsetse (Diptera: glossinidae) obligate symbiont Wigglesworthia. MBio. 2012 Feb 14;3(1). pii: e00240-11. doi: 10.1128/mBio.00240-11. Print 2012. PubMed PMID: 22334516; PubMed Central PMCID: PMC3280448. Hamilton JP, Neeno-Eckwall EC, Adhikari BN, Perna NT, Tisserat N, Leach JE, Lévesque CA, Buell CR. The Comprehensive Phytopathogen Genomics Resource: a web-based resource for data-mining plant pathogen genomes. Database (Oxford). 2011 Nov 26;2011:bar053. Print 2011. PubMed PMID: 22120664; PubMed Central PMCID: PMC3225079. Baumler DJ, Peplinski RG, Reed JL, Glasner JD, Perna NT. The evolution of metabolic networks of E. coli. BMC Syst Biol. 2011 Nov 1;5:182. PubMed PMID: 22044664; PubMed Central PMCID: PMC3229490. Glasner JD, Yang CH, Reverchon S, Hugouvieux-Cotte-Pattat N, Condemine G, Bohin JP, Van Gijsegem F, Yang S, Franza T, Expert D, Plunkett G 3rd, San Francisco MJ, Charkowski AO, Py B, Bell K, Rauscher L, Rodriguez-Palenzuela P, Toussaint A, Holeva MC, He SY, Douet V, Boccara M, Blanco C, Toth I, Anderson BD, Biehl BS, Mau B, Flynn SM, Barras F, Lindeberg M, Birch PR, Tsuyumu S, Shi X, Hibbing M, Yap MN, Carpentier M, Dassa E, Umehara M, Kim JF, Rusch M, Soni P, Mayhew GF, Fouts DE, Gill SR, Blattner FR, Keen NT, Perna NT. Genome sequence of the plant-pathogenic bacterium Dickeya dadantii 3937. J Bacteriol. 2011 Apr;193(8):2076-7. Epub 2011 Jan 7. PubMed PMID: 21217001; PubMed Central PMCID: PMC3133054. Torto-Alalibo T, Collmer CW, Gwinn-Giglio M, Lindeberg M, Meng S, Chibucos MC, Tseng TT, Lomax J, Biehl B, Ireland A, Bird D, Dean RA, Glasner JD, Perna N, Setubal JC, Collmer A, Tyler BM. Unifying themes in microbial associations with animal and plant hosts described using the gene ontology. Microbiol Mol Biol Rev. 2010 Dec;74(4):479-503. Review.PMID: 21119014 Darling AE, Mau B, Perna NT. progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One. 2010 Jun 25;5(6):e11147. PubMed PMID: 20593022; PubMed Central PMCID: PMC2892488. Dufour YS, Wesenberg GE, Tritt AJ, Glasner JD, Perna NT, Mitchell JC, Donohue TJ. chipD: a web tool to design oligonucleotide probes for high-density tiling arrays. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W321-5. Epub 2010 Jun 6. PubMed PMID: 20529880; PubMed Central PMCID: PMC2896189. Rodríguez-Palenzuela P, Matas IM, Murillo J, López-Solanilla E, Bardaji L, Pérez- Martínez I, Rodríguez-Moskera ME, Penyalver R, López MM, Quesada JM, Biehl

4 BS, Perna NT, Glasner JD, Cabot EL, Neeno-Eckwall E, Ramos C. Annotation and overview of the Pseudomonas savastanoi pv. savastanoi NCPPB 3335 draft genome reveals the virulence gene complement of a tumour-inducing pathogen of woody hosts. Environ Microbiol. 2010 Jun;12(6):1604-20. Epub 2010 Apr 1. PubMed PMID: 20370821. Sebaihia M, Bocsanczy AM, Biehl BS, Quail MA, Perna NT, Glasner JD, DeClerck GA, Cartinhour S, Schneider DJ, Bentley SD, Parkhill J, Beer SV. Complete genome sequence of the plant pathogen Erwinia amylovora strain ATCC 49946. J Bacteriol. 2010 Apr;192(7):2020-1. Epub 2010 Jan 29. PubMed PMID: 20118253; PubMed Central PMCID: PMC2838050. Rissman AI, Mau B, Biehl BS, Darling AE, Glasner JD, Perna NT. Reordering contigs of draft genomes using the Mauve aligner. Bioinformatics. 2009 Aug 15;25(16):2071-3. Epub 2009 Jun 10. PubMed PMID: 19515959; PubMed Central PMCID: PMC2723005. Zaremba S, Ramos-Santacruz M, Hampton T, Shetty P, Fedorko J, Whitmore J, Greene JM, Perna NT, Glasner JD, Plunkett G 3rd, Shaker M, Pot D. Text-mining of PubMed abstracts by natural language processing to create a public knowledge base on molecular mechanisms of bacterial enteropathogens. BMC Bioinformatics. 2009 Jun 10;10:177. PubMed PMID: 19515247; PubMed Central PMCID: PMC2704210. Harris DR, Pollock SV, Wood EA, Goiffon RJ, Klingele AJ, Cabot EL, Schackwitz W, Martin J, Eggington J, Durfee TJ, Middle CM, Norton JE, Popelars MC, Li H, Klugman SA, Hamilton LL, Bane LB, Pennacchio LA, Albert TJ, Perna NT, Cox MM, Battista JR. Directed evolution of ionizing radiation resistance in Escherichia coli. J Bacteriol. 2009 Aug;191(16):5240-52. Epub 2009 Jun 5. PubMed PMID: 19502398; PubMed Central PMCID: PMC2725583. Kim HS, Ma B, Perna NT, Charkowski AO. Phylogeny and virulence of naturally occurring type III secretion system-deficient Pectobacterium strains. Appl Environ Microbiol. 2009 Jul;75(13):4539-49. Epub 2009 May 1. PubMed PMID: 19411432; PubMed Central PMCID: PMC2704834. Lindeberg M, Biehl BS, Glasner JD, Perna NT, Collmer A, Collmer CW. Gene Ontology annotation highlights shared and divergent pathogenic strategies of type III effector proteins deployed by the plant pathogen Pseudomonas syringae pv tomato DC3000 and animal pathogenic Escherichia coli strains. BMC Microbiol. 2009 Feb 19;9 Suppl 1:S4. Review. PubMed PMID: 19278552; PubMed Central PMCID: PMC2654664. Glasner JD, Marquez-Villavicencio M, Kim HS, Jahn CE, Ma B, Biehl BS, Rissman AI, Mole B, Yi X, Yang CH, Dangl JL, Grant SR, Perna NT, Charkowski AO. Niche- specificity and the variable fraction of the Pectobacterium pan-genome. Mol Plant Microbe Interact. 2008 Dec;21(12):1549-60. PubMed PMID: 18986251. Baumler DJ, Hung KF, Glasner JD, Perna NT. Annotation of the bacteriophage 933W genome: an in-class interactive web-based exercise. ASM Microbe Library, 9/30/08. Ma B, Hibbing ME, Kim HS, Reedy RM, Yedidia I, Breuer J, Breuer J, Glasner JD, Perna NT, Kelman A, Charkowski AO. Host range and molecular phylogenies of the soft rot enterobacterial genera Pectobacterium and Dickeya. Phytopathology. 2007 Sep;97(9):1150-63. PubMed PMID: 18944180.

5 Mayhew GF, Bartholomay LC, Kou HY, Rocheleau TA, Fuchs JF, Aliota MT, Tsao IY, Huang CY, Liu TT, Hsiao KJ, Tsai SF, Yang UC, Perna NT, Cho WL, Christensen BM, Chen CC. Construction and characterization of an expressed sequenced tag library for the mosquito vector Armigeres subalbatus. BMC Genomics. 2007 Dec 18;8:462. PubMed PMID: 18088419; PubMed Central PMCID: PMC2262096. Darling AE, Treangen TJ, Messeguer X, Perna NT. Analyzing patterns of microbial evolution using the mauve genome alignment system. Methods Mol Biol. 2007;396:135-52. PubMed PMID: 18025691. Glasner JD, Plunkett G 3rd, Anderson BD, Baumler DJ, Biehl BS, Burland V, Cabot EL, Darling AE, Mau B, Neeno-Eckwall EC, Pot D, Qiu Y, Rissman AI, Worzella S, Zaremba S, Fedorko J, Hampton T, Liss P, Rusch M, Shaker M, Shaull L, Shetty P, Thotakura S, Whitmore J, Blattner FR, Greene JM, Perna NT. Enteropathogen Resource Integration Center (ERIC): bioinformatics support for research on biodefense-relevant enterobacteria. Nucleic Acids Res. 2008 Jan;36(Database issue):D519-23. Epub 2007 Nov 13. PubMed PMID: 17999997; PubMed Central PMCID: PMC2238966. Greene JM, Plunkett G 3rd, Burland V, Glasner J, Cabot E, Anderson B, Neeno-Eckwall E, Qiu Y, Mau B, Rusch M, Liss P, Hampton T, Pot D, Shaker M, Shaull L, Shetty P, Shi C, Whitmore J, Wong M, Zaremba S, Blattner FR, Perna NT. A new asset for pathogen informatics--the Enteropathogen Resource Integration Center (ERIC), an NIAID Bioinformatics Resource Center for Biodefense and Emerging/Re-emerging Infectious Disease. Adv Exp Med Biol. 2007;603:28-42. PubMed PMID: 17966403. Mau B, Glasner JD, Darling AE, Perna NT. Genome-wide detection and analysis of homologous recombination among sequenced strains of Escherichia coli. Genome Biol. 2006;7(5):R44. Epub 2006 May 31. PubMed PMID: 16737554; PubMed Central PMCID: PMC1779527. Anderson BD, Gilson MC, Scott AA, Biehl BS, Glasner JD, Rajashekara G, Splitter GA, Perna NT. CGHScan: finding variable regions using high-density microarray comparative genomic hybridization data. BMC Genomics. 2006 Apr 25;7:91. PubMed PMID: 16638145; PubMed Central PMCID: PMC1464128. Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G 3rd, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL. Escherichia coli K- 12: a cooperatively developed annotation snapshot--2005. Nucleic Acids Res. 2006 Jan 5;34(1):1-9. Print 2006. PubMed PMID: 16397293; PubMed Central PMCID: PMC1325200. Glasner JD, Rusch M, Liss P, Plunkett G 3rd, Cabot EL, Darling A, Anderson BD, Infield-Harm P, Gilson MC, Perna NT. ASAP: a resource for annotating, curating, comparing, and disseminating genomic data. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D41-5. PubMed PMID: 16381899; PubMed Central PMCID: PMC1347526. Okinaka Y, Perna NT, Yang S, Keen NT, Yang CH. Identification of new virulence genes in Erwinia chrysanthemi 3937; Transposon insertion into plant up-regulated genes. J. Gen. Plant Pathology 2006 72(6): 360-368.

6 Mau B, Darling AE, Perna NT. Identifying evolutionarily conserved segments among multiple divergent and rearranged genomes. In Comparative Genomics RECOMB 2004 International Workshop, RCG, Bertinoro, Italy, October 16-19, 2004, Revised Selected Papers; Series: Lecture Notes in Computer Science, Subseries: Lecture Notes in Bioinformatics, Vol. 3388 Lagergren, Jens (Ed.) 2005. Yang S, Perna NT, Cooksey DA, Okinaka Y, Lindow SE, Ibekwe AM, Keen NT, Yang CH. Genome-wide identification of plant-upregulated genes of Erwinia chrysanthemi 3937 using a GFP-based IVET leaf array. Mol Plant Microbe Interact. 2004 Sep;17(9):999-1008. PubMed PMID: 15384490. Darling AC, Mau B, Blattner FR, Perna NT. Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res. 2004 Jul;14(7):1394-403. PubMed PMID: 15231754; PubMed Central PMCID: PMC442156. Bartholomay LC, Cho WL, Rocheleau TA, Boyle JP, Beck ET, Fuchs JF, Liss P, Rusch M, Butler KM, Wu RC, Lin SP, Kuo HY, Tsao IY, Huang CY, Liu TT, Hsiao KJ, Tsai SF, Yang UC, Nappi AJ, Perna NT, Chen CC, Christensen BM. Description of the transcriptomes of immune response-activated hemocytes from the mosquito vectors Aedes aegypti and Armigeres subalbatus. Infect Immun. 2004 Jul;72(7):4114-26. PubMed PMID: 15213157; PubMed Central PMCID: PMC427405. Kudva IT, Griffin RW, Murray M, John M, Perna NT, Barrett TJ, Calderwood SB. Insertions, deletions, and single-nucleotide polymorphisms at rare restriction enzyme sites enhance discriminatory power of polymorphic amplified typing sequences, a novel strain typing system for Escherichia coli O157:H7. J Clin Microbiol. 2004 Jun;42(6):2388-97. PubMed PMID: 15184409; PubMed Central PMCID: PMC427851. Darling AE, Mau B, Blattner FR, Perna NT. GRIL: genome rearrangement and inversion locator. Bioinformatics. 2004 Jan 1;20(1):122-4. PubMed PMID: 14693819. Lathem WW, Bergsbaken T, Witowski SE, Perna NT, Welch RA. Acquisition of stcE, a C1 esterase inhibitor-specific metalloprotease, during the evolution of Escherichia coli O157:H7. J Infect Dis. 2003 Jun 15;187(12):1907-14. Epub 2003 Jun 4. PubMed PMID: 12792867. Wei J, Goldberg MB, Burland V, Venkatesan MM, Deng W, Fournier G, Mayhew GF, Plunkett G 3rd, Rose DJ, Darling A, Mau B, Perna NT, Payne SM, Runyen-Janecky LJ, Zhou S, Schwartz DC, Blattner FR. Complete genome sequence and comparative genomics of Shigella flexneri serotype 2a strain 2457T. Infect Immun. 2003 May;71(5):2775-86. Erratum in: Infect Immun. 2003 Jul;71(7):4223. PubMed PMID: 12704152; PubMed Central PMCID: PMC153260. Glasner JD, Liss P, Plunkett G 3rd, Darling A, Prasad T, Rusch M, Byrnes A, Gilson M, Biehl B, Blattner FR, Perna NT. ASAP, a systematic annotation package for community analysis of genomes. Nucleic Acids Res. 2003 Jan 1;31(1):147-51. PubMed PMID: 12519969; PubMed Central PMCID: PMC165572. Welch RA, Burland V, Plunkett G 3rd, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc

7 Natl Acad Sci U S A. 2002 Dec 24;99(26):17020-4. Epub 2002 Dec 5. PubMed PMID: 12471157; PubMed Central PMCID: PMC139262. Zhou S, Deng W, Anantharaman TS, Lim A, Dimalanta ET, Wang J, Wu T, Chunhong T, Creighton R, Kile A, Kvikstad E, Bechner M, Yen G, Garic-Stankovic A, Severin J, Forrest D, Runnheim R, Churas C, Lamers C, Perna NT, Burland V, Blattner FR, Mishra B, Schwartz DC. A whole-genome shotgun optical map of Yersinia pestis strain KIM. Appl Environ Microbiol. 2002 Dec;68(12):6321-31. PubMed PMID: 12450857; PubMed Central PMCID: PMC134435. Torres AG, Giron JA, Perna NT, Burland V, Blattner FR, Avelino-Flores F, Kaper JB. Identification and characterization of lpfABCC'DE, a fimbrial operon of enterohemorrhagic Escherichia coli O157:H7. Infect Immun. 2002 Oct;70(10):5416- 27. PubMed PMID: 12228266; PubMed Central PMCID: PMC128367. Torres AG, Perna NT, Burland V, Ruknudin A, Blattner FR, Kaper JB. Characterization of Cah, a calcium-binding and heat-extractable autotransporter protein of enterohaemorrhagic Escherichia coli. Mol Microbiol. 2002 Aug;45(4):951-66. PubMed PMID: 12180916. Taylor DE, Rooker M, Keelan M, Ng LK, Martin I, Perna NT, Burland NT, Blattner FR. Genomic variability of O islands encoding tellurite resistance in enterohemorrhagic Escherichia coli O157:H7 isolates. J Bacteriol. 2002 Sep;184(17):4690-8. PubMed PMID: 12169592; PubMed Central PMCID: PMC135296. Deng W, Burland V, Plunkett G 3rd, Boutin A, Mayhew GF, Liss P, Perna NT, Rose DJ, Mau B, Zhou S, Schwartz DC, Fetherston JD, Lindler LE, Brubaker RR, Plano GV, Straley SC, McDonough KA, Nilles ML, Matson JS, Blattner FR, Perry RD. Genome sequence of Yersinia pestis KIM. J Bacteriol. 2002 Aug;184(16):4601-11. PubMed PMID: 12142430; PubMed Central PMCID: PMC135232. Okinaka Y, Yang CH, Perna NT, Keen NT. Microarray profiling of Erwinia chrysanthemi 3937 genes that are regulated during plant infection. Mol Plant Microbe Interact. 2002 Jul;15(7):619-29. PubMed PMID: 12118877. Yang CH, Gavilanes-Ruiz M, Okinaka Y, Vedel R, Berthuy I, Boccara M, Chen JW, Perna NT, Keen NT. hrp genes of Erwinia chrysanthemi 3937 are important virulence factors. Mol Plant Microbe Interact. 2002 May;15(5):472-80. PubMed PMID: 12036278. Kudva IT, Evans PS, Perna NT, Barrett TJ, DeCastro GJ, Ausubel FM, Blattner FR, Calderwood SB. Polymorphic amplified typing sequences provide a novel approach to Escherichia coli O157:H7 strain typing. J Clin Microbiol. 2002 Apr;40(4):1152-9. PubMed PMID: 11923324; PubMed Central PMCID: PMC140341. Kudva IT, Evans PS, Perna NT, Barrett TJ, Ausubel FM, Blattner FR, Calderwood SB. Strains of Escherichia coli O157:H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms. J Bacteriol. 2002 Apr;184(7):1873-9. PubMed PMID: 11889093; PubMed Central PMCID: PMC134921. Heimer SR, Welch RA, Perna NT, Pósfai G, Evans PS, Kaper JB, Blattner FR, Mobley HL. Urease of enterohemorrhagic Escherichia coli: evidence for regulation by fur and a trans-acting factor. Infect Immun. 2002 Feb;70(2):1027-31. PubMed PMID: 11796646; PubMed Central PMCID: PMC127683.

8 Lim A, Dimalanta ET, Potamousis KD, Yen G, Apodoca J, Tao C, Lin J, Qi R, Skiadas J, Ramanathan A, Perna NT, Plunkett G 3rd, Burland V, Mau B, Hackett J, Blattner FR, Anantharaman TS, Mishra B, Schwartz DC. Shotgun optical maps of the whole Escherichia coli O157:H7 genome. Genome Res. 2001 Sep;11(9):1584-93. PubMed PMID: 11544203; PubMed Central PMCID: PMC311123. Perna NT, Plunkett G 3rd, Burland V, Mau B, Glasner JD, Rose DJ, Mayhew GF, Evans PS, Gregor J, Kirkpatrick HA, Pósfai G, Hackett J, Klink S, Boutin A, Shao Y, Miller L, Grotbeck EJ, Davis NW, Lim A, Dimalanta ET, Potamousis KD, Apodaca J, Anantharaman TS, Lin J, Yen G, Schwartz DC, Welch RA, Blattner FR. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature. 2001 Jan 25;409(6819):529-33. Erratum in: Nature 2001 Mar 8;410(6825):240. PubMed PMID: 11206551. Ffrench-Constant RH, Waterfield N, Burland V, Perna NT, Daborn PJ, Bowen D, Blattner FR. A genomic sample sequence of the entomopathogenic bacterium Photorhabdus luminescens W14: potential implications for virulence. Appl Environ Microbiol. 2000 Aug;66(8):3310-29. PubMed PMID: 10919786; PubMed Central PMCID: PMC92150. Burland V, Shao Y, Perna NT, Plunkett G, Sofia HJ, Blattner FR. The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7. Nucleic Acids Res. 1998 Sep 15;26(18):4196-204. PubMed PMID: 9722640; PubMed Central PMCID: PMC147824. Perna NT, Mayhew GF, Pósfai G, Elliott S, Donnenberg MS, Kaper JB, Blattner FR. Molecular evolution of a pathogenicity island from enterohemorrhagic Escherichia coli O157:H7. Infect Immun. 1998 Aug;66(8):3810-7. PubMed PMID: 9673266; PubMed Central PMCID: PMC108423. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y. The complete genome sequence of Escherichia coli K- 12. Science. 1997 Sep 5;277(5331):1453-62. PubMed PMID: 9278503. Perna NT, Kocher TD. Mitochondrial DNA: molecular fossils in the nucleus. Curr Biol. 1996 Feb 1;6(2):128-9. Review. PubMed PMID: 8673455. Perna NT, Kocher, TD. Unequal Base Frequencies and the Estimation of Substitution Rates. Molecular Biology and Evolution, 1995; 12:359-361. Perna NT, Kocher TD. Patterns of nucleotide composition at fourfold degenerate sites of animal mitochondrial genomes. J Mol Evol. 1995 Sep;41(3):353-8. PubMed PMID: 7563121. Perna NT, Batzer MA, Deininger PL, Stoneking M. Alu insertion polymorphism: a new type of marker for human population studies. Hum Biol. 1992 Oct;64(5):641-8. PubMed PMID: 1328024.

Publications in Edited Books: E. Mettert, N.T. Perna, P.J. Kiley. Sensing the cellular Fe-S cluster demand: a structural, functional, and phylogenetic overview of Escherichia coli IscR. De Gruyter Publisher,

9 Berlin, in “Iron-sulfur Clusters in Chemistry and Biology”. Ed. by Rouault, Tracey. 2014 pp 325-346. N.T. Perna. “Genomics of Escherichia and Shigella” in Genomics of Foodborne Pathogens, Springer, New York, 2011, pp. 119-140. J.M. Greene, G. Plunkett III, V. Burland, J.D. Glasner, E. Cabot, B.D. Anderson, E. Neeno-Eckwall, Y. Qiu, R. Mau, M. Rusch, P. Liss, T. Hampton, D. Pot, M. Shaker, L. Shaull, P. Shetty, C. Shi, J. Whitmore, M. Wong, S. Zaremba, F.R. Blattner, and N.T. Perna “A New Asset for Pathogen Informatics – the Enteropathogen Resource Integration Center (ERIC), an NIAID Bioinformatics Resource Center for Biodefense and Emerging/Re-emerging Infectious Disease” in The Genus Yersinia: From Genomics to Function, Springer, New York. Adv Exp Med Biol. 2007;603:28-42. A. E. Darling, T.J. Treangen, X. Messegeur, N.T. Perna. Analyzing patterns of microbial evolution using the Mauve genome alignment system. Methods Mol Biol. 2007;396:135-52. Glasner, J.D. and N.T. Perna. Genomics of Enterobacteriaceae. In Ed. L.B. Jorde, P. Little, M. Dunn and S. Subramaniam, eds. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics, John Wiley & Sons, Ltd., London, UK, 2005. Perna, N. T., J. D. Glasner, V. Burland and G. Plunkett III. The Genomes of Escherichia coli K-12 and Pathogenic E. coli. In M.S. Donnenberg, ed. Escherichia coli: Virulence Mechanisms of a Versatile Pathogen, Academic Press, New York, N.Y. 2002. Kaper, J.B., S. Elliott, V. Sperandio, N. T. Perna, G. F. Mayhew, and F. R. Blattner, 1998. Attaching and effacing intestinal histopathology and the locus of enterocyte effacement. In Kaper, J. B., O'Brien, A.D., eds. Escherichia coli O157:H7 and other shigella toxin production E.coli strains, ASM Press, Washington D.C. pp 163-182.

Other Publications: J. D. Glasner and N.T. Perna. Comparative Genomics of Escherichia coli. Microbiology Today, Quarterly Magazine of the Society for General Microbiology, E. coli issue, August 2004.

Select National or International Presentations by Lab Members: “ Paleo Systems Biology: Investigating Modern-Day Disease by Using Metabolic Models of Bacteria from the Past”, American Society for Microbiologists Annual Meeting, San Francisco, CA, 6/2012. Presented by postdoc David Baumler. “Examining the Root of Plant Disease Using Metabolic Models of Plant Pathogens”. American Society for Microbiologists Annual Meeting, San Francisco, CA, 6/2012. Presented by graduate student Bryan Biehl. “Generation of a metabolic network representing the ancestral core of the family Enterobacteriaceae.” 1st Conference on Constraint-based Reconstruction and Analysis held June 24th-26th in Reykjavik, Iceland, 6/2011. Presented by postdoc David Baumler.

10 “Generation of computational metabolic models of three strains of Escherichia coli and growth comparisons in the presence or absence of oxygen.” BioMicroWorld: the 3rd International Conference on Environmental, Industrial, and Applied Microbiology held in Lisbon, Portugal 12/2009. Presented by postdoc David Baumler.

Invited Oral Presentations at National or International Conferences: “Navigating incongruence and uncertainty in genome-scale phylogenetic and ancestral state reconstructions of enterobacteria”, RECOMB-Comparative Genomics; Frankfurt, Germany; Oct 7, 2016 “Reconstructing the origin of adaptation to and pathogenicity of plant-associated enterobacteria”, Canadian Society of Microbiologists, Regina, Saskatchewan, Summer 2015 “Evolution of oxygen-responsive regulatory and metabolic networks”, International Small Genomes Conference, Lake Arrowhead, CA; Sept 2014 “Genomic approaches to studying evolution of metabolic pathways and regulatory networks”, Session chair and speaker, American Society for Microbiologists, Annual Meeting, San Diego, CA, May 2009, cancelled due to personal reasons. "Genomic perspectives on plant-associated enterobacteria", American Phytopathology Society Annual Conference, August 2009, presented by graduate student Bryan Biehl in lieu of cancellation due to personal reasons. “The pan-genome of enterobacteria”, 2nd American Society for Microbiologists Beneficial Microbes Conference, San Diego, CA; Oct 12-16, 2008. "Recent advances in microbial genomics", American Society for Microbiologists, Annual Meeting, Boston, MA, May 2008, canceled due to personal reasons. “Challenges and Rewards of Collaborative Comparative Genomics”, International Collaborations in Cyberinfrastructure-Enabled Genomics Workshop, funded by the U.S. National Science Foundation (award number 0742675), and CONCYTEC (PERU), Universidad Peruana Cayetano Heredia; Lima, Peru; Jan 15-19, 2008. U.S. Genomics keynote speaker. "Progressive approaches to multiple genome alignment and regulatory evolution", Ecology and Evolution of Infectious Diseases Meeting, sponsored by corresponding NIGMS and NSF programs, Albuquerque, NM, Dec. 4-6, 2007. “Plants, Animals (and Insects too) – Host Specialization and Genome Evolution of Enterobacteria, The 11th International Conference on Plant Pathogenic Bacteria, Edinburgh, Scotland, July 9-14, 2006. Keynote Talk. “Plants, Animals (and Insects too) – Host Specialization and Genome Evolution of Enterobacteria, Society for Molecular Biology and Evolution Annual Meeting, Tempe, AZ, May 24-28, 2006. “Alignment and Detection of intraspecific homologous recombination in Escherichia coli genomes”, 8th Annual Conference on Computational Genomics, Cambridge, Massachusetts, November 9-12, 2005.

11 “Genomes, Species, Populations”, 105th General Meeting of the American Society for Microbiology, Colloquium: Interpreting Microbial Diversity, Atlanta, Georgia, June 5- 10, 2005. “Comparative and functional analyses of the genomes formerly known as Erwinia”, USDA/NSF Microbial Genome Awardee Workshop, XII Plant and Animal Genomes Meeting, San Diego, CA, January 16, 2005. “Phylogenetic and Genomic Perspectives on Plant- and Animal-associated Bacteria”, 104th General Meeting of the American Society for Microbiology, Symposium: The Making of Metabolic Modules, New Orleans, LA, May 22-27, 2004. “Annotation and Analysis of Bacterial Genomes”, USDA/NSF Microbial Genome Awardee Workshop, National Science Foundation, Arlington, VA, January 16-17, 2004. “ASAP, Community annotation of the E. coli K-12 Genome”, The 2003 Molecular Genetics of Bacteria and Phages Meeting, University of Wisconsin, Madison, August 5-10, 2003. “Genome sequencing and analysis of Erwinia chrysanthemi 3937”, USDA/NSF Microbial Genome Awardee Workshop, ASM and TIGR Conference on Microbial Genomics, Fairmont Hotel, New Orleans, Louisiana, January 29-February 1, 2003. “Evolutionary Analyses of E. coli genomes and Populations”, 10th International Conference on Microbial Genomes, Arrowhead, CA, September 8-12, 2002. “Future of Pathogen Genomics”, Evolution of Infectious Diseases, Bethesda, MD NIH, August 29-30, 2002. “Genome wide view of enterobacterial pathogen evolution”, Gordon Research Conference: Molecular Evolution, Ventura, CA, January 13-18, 2002. “Genome sequencing and analysis of Erwinia chrysanthemi 3937”, Plant, Animal and Microbe Genomes X, USDA/NSF Microbial Genome Awardee Workshop, San Diego, California, January 12-16, 2002. “Comparative genomics of enterobacterial pathogens”, Plant, Animal and Microbe Genomes X, Functional Genomics Session, San Diego, California, January 12-16, 2002. “Genome-scale comparisons of E. coli strains”, Molecular Genetics of Bacteria and Phages Meeting, University of Wisconsin-Madison, Session chair, Bacterial Genomics: Structure, Transposition and Recombination, July 31-Aug 5, 2001. “Evolutionary Dynamics of Enterobacterial Genomes”, 10th International Congress of Molecular Plant-Microbe Interactions, University of Wisconsin-Madison, July 10-14, 2001. “Natural variation among E. coli and other enterobacterial genomes”, Brazilian International Genome Conference, Angra dos Reis, Rio de Janeiro, Brazil, March 26- 29, 2001. Also served as international judge for student poster competition hosted by Nature magazine. “Enterobacterial Pathogen Genomics”, The New Biology: Technologies for Resolving Macromolecular Communication, Association of Biomolecular Resource Facilities, Comparative Genomics Session Chair, San Diego, California, February 24-27, 2001.

12 “Natural variation in Escherichia coli O157:H7”, 2nd FDA/FSI Extramural Research Annual Review, College Park, Maryland, December 5, 2000. “Enterobacterial Pathogen Genomics”, American Society for Microbiology 60th North Central Branch Regional Meeting, Marshfield, Wisconsin, October 6-7, 2000. “Bacterial Pathogen Genomics”, American Phytopathological Society, Symposium: Genomics of Plant-Associated Bacteria, New Orleans, Louisiana, August 12-16, 2000. “Natural variation in Escherichia coli O157:H7”, 1st FDA/FSI Extramural Research Annual Review, College Park, Maryland, December 7, 1999. “Comparative Genomics of E. coli K12, O157:H7 and Related Enterobacterial Pathogens”, in place of F. R. Blattner, American Society for Microbiology 99th General Meeting, Colloquium: Genomic Biology of Bacteria, Chicago, Illinois, May 30-June 3, 1999. “Comparative Genomics of E. coli and related enteric pathogens”, Istituto Pasteur Fondazione Cenci Bolognetti, Mining Bacteria Genomes, Roma, National Research Council, April 16-17, 1999. “Comparative Genomics of E. coli”, in place of F.R. Blattner, Annual Meeting of the Canadian Institute for Advanced Research Evolutionary Biology Program, Montreal Canada, July 1998. “Patterns of Base Composition and Substitution Biases in Animal mtDNA”, Annual Meeting of the ASN, SSE and SSB, McGill University, Montreal, June 1995.

Contributed Oral Presentations at National or International Conferences: “Phylogenetic and Genomic Perspectives on Plant- and Animal-associated Enterobacteria”, N.T. Perna and J.D. Glasner, Annual Meeting of American Phytopathology Society (APS), Anaheim CA, July 31-Aug. 4, 2004.

Invited Research Presentations at Academic Institutions: “Evolution of the response to oxygen in Enterobacteria”, Evolution Seminar Series, UW- Madison, March 6, 2014. “Evolution of the response to oxygen in Enterobacteria: Systems Biology of a Complex Trait”, SysBioM Seminar Series, UW-Madison, November 12, 2013. “Detecting balancing and directional selection in oxygen-response transcriptome data”. Genome Center of Wisconsin chalk talk, November 12, 2013. “Assembling the Tree of Life: the twisted and tangled enterobacteria branch”, MathBio4:Scale Symposium, Wisconsin Institutes of Discovery, University of Wisconsin-Madison, October 19, 2012. “Friends and Enemies - evolution of bacterial pathogen and nonpathogen genomes”, Applied Evolution Symposium, University of Wisconsin-Madison, October 2, 2010. “The pan-genome of enterobacteria”, Genetics Departmental Retreat, October, 2008. “Looking at the genomes of enterobacteria through Mauve-colored glasses”, University of Wisconsin-Madison, Evolution Seminar Series, March 6, 2008. “Looking at the genomes of enterobacteria through Mauve-colored glasses”, Oregon State University, Center for Genome Research and Biocomputing”, Jan 9, 2008.

13 “Measuring rates and patterns of genome evolution in enterobacteria”, Ohio State University, Department of Plant Pathology and Wooster Area Molecular Biology Association, May 27, 2005. “Comparative genomics of Enterobacteria”, Distinguished Speaker Series, University of Wisconsin – Milwaukee Center for Functional and Environmental Genomics, March 4, 2005. “What comparative genomics can tell us about soft-rot, diarrhea and the plague”, Genome Sciences Training Program Retreat, Pyle Center, University of Wisconsin, June 21, 2004. “Phylogenetic and Genomic Perspectives on Enterobacteria”, Annual Meeting of the Food Research Institute, Madison, Wisconsin May 18-19, 2004. “People, potatoes and pathogens”, All SVM Seminar Series, School of Veterinary Medicine, University of Wisconsin, February 18, 2004. “ASAP, Community Annotation of Genomes”, Computation and Informatics in Biology and Medicine Training Program Seminar Series, University of Wisconsin-Madison, Oct. 14, 2003. “Genome Sequencing and Analysis of Enterobacterial Phytopathogens”, Plant Pathology Department Seminar Series, University of Wisconsin-Madison, March 4, 2003. “Enterobacterial Genome Evolution”, IGERT Seminar Series, University of Indiana, Bloomington, IN, April 19, 2002. “The Genomes of Enterobacteriaceae”, Frontiers of Genomics V, University of Wisconsin-Madison, Madison, WI, May 17-18, 2001. “E. coli Genomics: Dynamics of Divergence”, Annual Meeting of the Food Research Institute, Madison, Wisconsin May 16-17, 2001. “E. coli: Good bug gone bad?”, Microbiology Departmental Seminar and Bioinformatics Course visiting speaker, University of Wisconsin-LaCrosse, April 6, 2001. “Comparative Genomics of E. coli and Related Enterobacterial Pathogens”, Veterinary Science Seminar Series, School of Veterinary Medicine, University of Wisconsin- Madison, October 18, 2000. “Natural Variation among E. coli genomes”, E. coli Group Meeting, University of Wisconsin-Madison, November 1, 2000. “Comparative Genomics of E. coli and Related Pathogens”, Department of Plant Pathology Seminar Series, University of Wisconsin-Madison, November 2, 1999. “Comparative Genomics of E. coli and Related Enterobacterial Pathogens”, Undergraduate Biology Colloquium, University of Wisconsin-Whitewater, March 5, 1999.

Workshops: “American Society for Microbiologists mini-colloquium on E. coli” sponsored by the American Academy for Microbiology, Washington D. C., Sept 2011, unable to participate due to personal reasons. “International Collaborations in Cyberinfrastructure-Enabled Genomics”, funded by the U.S. National Science Foundation under award number 0742675, and CONCYTEC

14 (PERU), Universidad Peruana Cayetano Heredia; Lima, Peru; Jan 15-19, 2008. Keynote speaker and workshop participant. “Genomics and Global Pathogens Colloquium”, sponsored by the American Acadamy of Microbiologists, Washington, DC, September 26-28, 2006. Rapporteur and one of 40 participants. “International Erwinia Workshop”, Dundee, Scotland, July 5-9, 2006. Participant. “Gene Ontology Annotation Camp”, Stanford University, Palo Alto, California, May 31 – June 3, 2005. Participant. “Community annotation and ERIC-BRC”, NIH-NIAID Microbial Genomes Program E. coli/Shigella Meeting, TIGR, Rockville, Maryland, Feb. 16, 2005. Presenter. “The Genome of the plant-pathogenic bacteria Erwinia chrysanthemi 3937: from genome annotation to post-genomic studies”, NSF/CNRS-sponsored International Joint Workshop at the Pyle Center, Madison, WI. Co-hosted by Nicole Perna and Guy Condemine. July 21-23, 2004. “Development of PAMGO (Plant Associated Microbe Gene Ontology) Terms”, The Institute for Genomic Research, April 23, 2004. Discussion participant. “E. coli K-12 Annotation Update”, Woods Hole Oceanographic Institute Marine Biological Laboratory, November 13-18, 2003. Discussion participant and annotator. “Genomics and Plant-Microbe Interactions”, Discussion Session with Joseph Jens, Undersecretary of the USDA, August 27, 2003. Discussion Participant “Disease Resistance in Plants and Animals U.S.-E.C. Task Force in Biotechnology Workshop”, Speaker: “Meeting the Challenges of Disease and Resistance with Genomics” and discussion participant. Washington Marriot, Washington D.C., June 23-24, 2003 “Ecmc2, E. coli Model Cell Consortium, Bioinformatics Resource Planning Workshop”, Bioinformatics Organizing Committee and Annotation Working Group Member, UCSD, San Diego, California, March 1-3, 2003. “Evolution of Virulence”, Evolution of Infectious Diseases, Bethesda, MD NIH. Co-chair with Paul Turner. August 29-30, 2002. “Workshop on Genomic Analysis of Plant-Associated Microorganisms”, sponsored by the American Phytopathological Society, April 9-11, 2002, Washington D.C.; discussion panel participant, white paper steering committee “Sequencing and Analysis of the Erwinia chrysanthemi 3937 Genome”, NSF/CNRS- sponsored International Joint Workshop in Lyon, France. Co-hosted by Nicole Perna and Nicole Hugouvieux Cotte-Pattat. July 2002

Research Funding

Pending Proposals: “Evolution of Regulatory and Metabolic Networks associated with the Response to Oxygen Availability”, NSF-MCB, submitted 11/15/2016.

15

Current Grants: “Identifying host interaction factors using supervised machine learning”, Hatch (PI N.T. Perna and Co-PI A. Charkowski); 9/1/2014-8/31/17; Total Costs: $217,389. “Teaching Evolution”, Educational Innovation Small Grant Program, UW-Madison; 7/1/2015-6/30/2017; $13,000.

Completed Research Grants: “ATOL: Assembling a taxonomically balanced genome-scale reconstruction of the evolutionary history of the Enterobacteriaceae”, NSF DEB-0936214 (PI N.T. Perna with Co-PIs Cecile Ane, Colin Dewey and Bret Larget); 9/1/2009 - 8/31/2016; Total Costs: $2,483,009. “Improving the Value of Plant Pathogen Genome Sequences Through Uniform, Updated, and Value-added Annotation”, USDA/NSF Award# #: 61-4222A (PI C. Robin Buell, MSU, Co-PI N.T. Perna); 9/1/2009 - 8/31/2012; Subcontract to Perna: $431.276 “Molecular Evolution of Microbial Pathogen Genomes”, NIH R01-GM62994 (PI. N.T. Perna with Co-PIs J.D. Glasner, P.J. Kiley); 05/01/2001-08/31/2011. Total Cost: $920,226 (second award only). “Great Lakes Bioenergy Research Center”; DOE DE-FC 02-07ER64494 (PI Tim Donohue, Thrust 3.2.3 Leader N.T. Perna); 9/01/07-09/29/10; Thrust 3.2.3: The goal of this thrust is to engineer E. coli capable of degrading cellulosic material through integration of naturally occurring pathways from other enterobacteria. “BACTER: Bringing Advanced Computational Techniques To Environmental Research”; DOE DE-FG02-04ER25627; (PI Julie Mitchell, Co-PI Perna); 11/01/04-8/31/11 “Genome-Enabled Analyses of Natural Populations of Pathogens on Natural Hosts”, NSF BE: GENOME-ENABLE ENVIR SCI&EN Program, Award# 0412599 (PI Amy Charkowski, Co-PIs Nicole T. Perna, Sarah Grant, Jeffrey Dangl), 09/15/04\09/14/09; Total Costs: $1,621,989 “Gene Ontology Terms for Standardized Annotation of Plant-associated Microbe Genomes”, NSF/USDA Microbial Genome Sequencing Program (PI Brett Tyler, Co- PIs Nicole T. Perna, Alan Collmer, Ralph Dean, Owen White), 10/1/05-9/30/08; Subcontract to Perna: $108,269 “Bioinformatics Resource Centers for Biodefense and Emerging/Re-emerging Infectious Disease”, NIH-NIAID-DMID-04-34 #97961, (PI, John Greene, SRA International, Inc.; UW Subcontract PI Nicole T. Perna), 07/01/04-06/30/09; Subcontract to Perna: $4,138,082 “Genome Sequencing and Analysis of Pantoea stewartii subsp. stewartii”, NSF/USDA Microbial Genome Sequencing Program AGRIC CSREES 2004-35600-14174, (PI Nicole T. Perna, Co-PI George Weinstock), 12/01/03-11/30/07. “Genome Sequencing and Analysis of Erwinia amylovora”, NSF/USDA Microbial Genome Sequencing Program, (PI Steven V. Beer, Co-PI Nicole T. Perna), 03/15/04- 09/14/07

16 “Genome Analysis of the plant pathogen, Erwinia chrysanthemi 3937”, Award#: INT- 0340700, NSF-International Opportunities for Scientists and Engineers-Joint Seminar/Workshop with CNRS (P.I. N. T. Perna with Co-P.I. Guy Condemine), 02/01/04-1/31/05. “Immune Response of Mosquitos to Filarial Worms”, NIH/NIAID R21 AI53772-01 (Co- investigator N. T. Perna with PI B. M. Christensen), 09/01/02-08/31/05. “Genome Sequencing and Analysis of Erwinia chrysanthemi”, USDA 2001-52100-11316 (P.I. N. T. Perna, Co-P.I.s N. T. Keen, F. R. Blattner), 9/19/01-3/31/04. “Natural Variation in Escherichia coli O157:H7”, FDA (Project Leader N. T. Perna with PI. F. R. Blattner), 9/98-3/01. “Genome Analysis of the plant pathogen, Erwinia chrysanthemi 3937”, Award#: INT- 0129203, NSF-International Opportunities for Scientists and Engineers-Joint Seminar/Workshop with CNRS (P.I. N. T. Perna with Co-P.I. Nicole H. Cotte-Pattat), 5/1/02-9/1/02.

Service Activities

Departmental Service Post Tenure Review Committee (2016 – present) Tenure and Mentoring Committees (2011 – present) Preliminary Examination Committee (2010 – present) Dept. of Genetics, Graduate Admissions Committee, 2006 – 2008 Dept. of Genetics, IT/Computing Committee, 2008 – 2009

Cross-departmental/Cross-college Service Evolution Coordinating Committee 2005 – present (chair) Crow Institute Graduate Committee Crow Institute Undergraduate Committee (chair) Crow Institute Outreach and Darwin Day Committee Crow Institute Seminar Committee Biology Major Program Committee, 2002-2009 and 2014 – present Genome Sciences Training Program Management Committee, 2004 – present Computational Biology for Undergraduates Committee 2004 – 2005 Global Biological Threats Initiative Steering Committee, 2006-2008 Genome Center Functional Genomics Hire Subcommittee, 2000-2002

University Level Service Graduate Faculty Executive Committee, 2015 – present (including 10-year review committees for Cancer Biology, Agronomy, Molecular and Environmental Toxicology grad programs) Microbiology Undergraduate Degree Program Review Committee, 2015 (chair) College of Agriculture and Life Sciences, Curriculum Committee, 2014 - 2015 Biological Sciences Divisional Tenure Committee, 2012 – 2015

17 CALS Dean Search and Screen Committee, 2011 Biological Sciences Divisional Strategic Planning Committee, 2008 – 2011 IBEWG, Committee on Undergraduate Biology Education, 2009 University of Wisconsin – Madison Reaccreditation Committee, 2009 School of Veterinary Medicine, Academic Planning Council, 2003 - 2006 School of Veterinary Medicine, Educational Policy Committee, 2003 – 2005 School of Veterinary Medicine, Information Technology Advisory Committee, 2001-2003

Other Professional Service Associate Editor, Molecular Biology and Evolution, 2015 – present Editorial Board, Microbial Genomics, 2014 – present NIH-NCAM Special Emphasis Panelist NSF Panelist, Ad hoc reviewer USDA-CSREES, Ad hoc reviewer Reviewer for various journals (~10/year) EcoCyc Scientific Advisory Board, Annual Reviewer, SRI, International, Menlo Park, CA, 2004 - 2006. Comprehensive Phytopathogen Genome Resource, Advisory Board, This new resource is being created by Robin Buell (TIGR), Jan Leach (Colorado State Univ.), Ned Tisserat (Colorado State Univ.), Tom Powers (University of Nebraska) and Andre Levesque (Ag Canada), 2006-2009 COMBREX (SciBay) Advisory Board – this NIH Grand-challenge initiative seeks to characterize the function of the growing legions of unknown proteins identified through genome sequencing, 2010-2013

Patents US Patent Number: 6,855,814 “Sequences of E. coli O157” US Patent Number: 6,365,723 “Sequences of E. coli O157” US Patent Number: 6,706,522 “Plasmid DNA from Yersinia pestis”

Teaching Overview I am passionate about teaching and mentoring undergraduates, graduate students and postdocs, and conducting STEM outreach to K-12 students and educators. I feel strongly that significant improvements in STEM education in the U.S., biomedical workforce diversity, and increases in the scientific literacy of our citizens in general, will require coordinated efforts across all of these levels. I am deeply committed to hands on approaches including active learning in the classroom, service-based learning that can provide opportunities for students to reach across audiences, and experience-based learning in general, such as mentored research in laboratories.

18 Current Courses at UW-Madison – I guest lecture in 2-3 courses per year ranging from freshman seminars to graduate level, but the core of my teaching at UW- Madison includes four courses. • Advanced Genomic and Proteomic Analysis is an intensive 3-credit graduate level course I have co-taught with Dr. Audrey Gasch every other fall since 2006. The goal of this course is to enable graduate students from biological science programs across campus to conduct “-Omics”-scale research. It includes lectures on fundamentals of analysis of genomes, metagenomes, proteomes, networks, and other types of big data, discussions of current literature, a weekly directed computer laboratory to build confidence and analytical skills, and an independent mentored research project using data relevant to each student’s graduate research. Many students enter the course with little to no experience and leave empowered to integrate across data types and leverage data across organisms to answer fundamental biological questions. • Comparative and Functional Genomics is a new 3-credit undergraduate course I will offer with Dr. John Pool every other spring. We are designing this course to fill a need for additional high-enrollment electives for upper level undergraduate Genetics Majors, and anticipate 60-80 students per year. It will cover essentially the same material taught in the graduate level course described above, with group active-learning exercises and team presentations substituting for the research projects and laboratory. Here the primary goals are to increase student awareness, knowledge and interest in experimental and analytical genomics methods that impact nearly all areas of modern biological sciences. • Undergraduate Evolution Seminar is a 1-credit course I have taught every spring since 2009. It is required for upper level Biology – Evolution Option Majors. Each week, students attend the campus evolution community’s standard research seminar series, not adjusted in any way for an undergraduate audience. After other attendees (faculty, postdocs and grad students) leave, the undergraduates hold a 1-hour discussion with the presenter with 1 or 2 students assigned to moderate. This course is designed to integrate students into the evolution community, expose them to diverse topics in current evolution research, and improve their oral and written science communication skills. With enrollment capped at 20 students, it is also an excellent checkpoint to evaluate the overall ability of students to synthesize information from their other educational experiences and assess whether the major is meeting its learning goals. • Teaching Evolution is a 2-credit course I have offered twice as a “topics course” that I plan to make a permanent offering for undergraduate and graduate students. The goal of this course is to prepare students to effectively communicate their knowledge of genetics and evolution to diverse audiences. Each week involves a lecture and small group exercise. Together, we explore educational research approaches, evidence-based best practices in pedagogy online and in person, challenges and misconceptions that make evolution a hard topic to teach, standards and expectations for K-12 and college students, and K-12 teacher professional development. Each student develops a lesson on evolution for an audience of their choice. They present the lesson to our class as a mock audience, and have the option to deliver it to their target audience for an additional credit transforming it into service-based learning. Projects have included an innovative “Predator-Prey Ballet” activity for K-2 girls, and an adaptation of an existing

19 middle/high school level DNA isolation protocol for elementary age students. Course development was funded in part by a UW-Madison Educational Innovation Award.

Teaching History “Exploring Biology” (Biology 100), guest lecture on evolution as a fundamental concept in biology in Freshman seminar course, 2015 “Evolution” (Zoo410), guest lecture on horizontal gene transfer and tree of life, April 2012, 2013, 2014. “Topics in Microbiology”, Core Introductory Series for new students in the Microbiology Doctoral Training Program, Profs. Tim Donohue and Ned Ruby, 2 week chalk- talk/discussion conducted on the relative merits of draft vs. complete genome sequencing, Fall 2005, Fall 2011. “Introductory Biology” (Zoology 151), Genetics Unit, Fall 2004, 2005, 2006, 3 credit 3 unit course co-taught with two additional faculty that vary by semester “Comparative Microbial Genomics”, 3 credit course focusing on the biological implications of microbial genome sequencing and functional analyses, Spring 2002, Fall 2003. “Statistical Methods in Genome Research”, 3 credit course aimed at developing an intuitive understanding of the fundamental distributions and statistics required for modern bioinformatics, Fall 2002 co-taught with Bob Mau. “Mechanism of Microbial Pathogenesis (MMI 740), Assoc. Prof. Joe Dillard, guest lecture given on the potential of bioinformatics to provide insight into pathogenesis, Oct 2005. “Sequence Analysis” (Biochem 711), Prof. Ann Palmenberg, guest lecture given on genome analysis, genome structure and sequence assembly, Nov. 2004. "Techniques in Bioinformatics and Comparative Genomics" short course lecturer, BioPharmaceutical Technology Center Institute, Fitchburg, Wisconsin, June, 2000, August 2001, June 2002, August 2003. “Evolutionary Functional Genomics”, Hosted by Asst. Prof. Carol E. Lee, Dept. of Zoology, Spring 2001: guest lecture given, attend weekly discussion group, assisted student project to analyze EST data from Schistosome genome project. “Molecular Techniques”, Prof. Judd Aiken, Dept. of Animal Health and Biomedical Sciences, Spring 2001: 3 lectures (genomics component). “Genomic Sciences”, Prof. David C. Schwartz, Dept. of Chemistry, 2001: guest lecture given on comparative genomics. Outreach Activities “Darwin Day”, Feb 2013-2017– organizer and exploration station host

“Advanced Placement Summer Institute Teacher Workshop”, June 2015, 2016

“Evolution - Active Learning Workshop for High School and Middle School Teachers”, Annual Conference of the Wisconsin Society of Science Teachers, Appleton 2014, Wisconsin Dells 2015, Lacrosse 2016, Oconomowoc 2017.

20 “Family Science Night”, Exploration Station host - Glendale Elementary School 2015, Leopold Elementary School 2015, Red Caboose After School Program 2016, Marquette Elementary School 2016.

“Uncovering the secrets of genomics”, University League Lecture Series, Holiday Inn West, Madison, WI, October, 17, 2001.

“One way to become a scientist”, National Honor Society Induction Ceremony, Emmaus Sr. High School, Emmaus, Pennsylvania, May 25, 2001.

“Genomics”, Madison Central Lions Club, arranged through the UW-Speaker’s Bureau, Office of the Chancellor, March 14, 2000.

Mentoring:

Research Scientists

Jeremy Glasner (2003-present). Jeremy has had a role in many different projects (5 publications, 15 co-authored). He was a co-PI on our NIH project examining regulatory evolution, analyzed genome-scale variation among plant pathogenic enterobacteria, and designed many aspects of the ASAP database, to name a few.

Eric Neeno-Eckwall (2007-present). Eric is currently our primary genome curator for the ASAP database and splits his time between developing new approaches to improving and augmenting annotations, and populating both our database and GenBank with the results (5 co-authored publications).

Guy Plunkett, III (2011-present). Guy officially joined my group in 2011 upon the retirement of Fred Blattner, but has been supported by awards in my name since 2005 (6 coauthored publications). From 2005-2009 he served as the head curator of the ERIC- BRC database. Since then, he has been the coordinator of our Tree of Life project dedicated to understanding the relationships between all named species of enterobacteria. His appointment in my group is 30% effort and he is also employed by DNASTAR where he assists with development of software for sequence analysis.

Fang Yang (2015-present). Fang is working on reticulate evolution of enterobacteria using a quartet based approach and high-throughput computing.

Gabriella Hammerlinck (2015-present). Gaby is a BioQUEST postdoc working on developing and implementing modules to introduce quantitative biology into standard biology curricula.

21 Robert Mau (2000-2010). Bob focused primarily on development of statistical methods for genome alignment which were ultimately incorporated into our Mauve genome aligner software (4 co-authored publications). He applied these methods to investigate the extent of recombination among E. coli strains (1 publication) and to comparative annotation of related genomes (3 co-authored publications). He also contributed to our NIH ERIC-BRC database (2 co-authored publications). Bob is currently employed as a research scientist in the laboratory of Laurence Loewe (UW-Madison, Dept. of Genetics/WID).

Eric Cabot (2006-2009). Eric was a genome curator for our NIH ERIC-BRC database team focusing on detection and annotation of pseudogenes and resolution of gene boundaries based on comparative analysis. After leaving my laboratory, he worked under my direction from 2009-2011 as the lead bioinformatician for the UW Biotech Center core facilty for analysis of next-generation sequence data. He is currently employed by DNASTAR in Madison, Wisconsin.

David Bowen (2006). Dave spent his short time (<6 months) in my group working as a genome curator for our ERIC-BRC database. He left the group to become a research scientist at Monsanto, St. Louis, Missouri.

Postdoctoral Fellows

David J. Baumler (2007-2013). Dave began as a member of our NIH ERIC-BRC database team curating genomes of enterobacteria with specific emphasis on more comprehensive identification and annotation of virulence factors (1 coauthored publication). He also had a strong interest in teaching and developed and tested two active-learning computational exercises for undergraduates on genome annotation (2 publications). He was awarded fellowships from the DOE-funded BACTER program (2009-10) and the NLM CIBM training program (2010-2012) allowing him advanced cross-training in bioinformatics. Under these awards, he worked on genome-scale metabolic modeling for extant and ancestral enterobacteria (1 publication, 1 submitted, 1 in prep). Dave just began a faculty position in the Department of Food Science, University of Minnesota. Invited Presentations: “ Paleo Systems Biology: Investigating Modern-Day Disease by Using Metabolic Models of Bacteria from the Past”, ASM Annual Meeting, San Francisco, CA, 6/2012. “Generation of a metabolic network representing the ancestral core of the family Enterobacteriaceae.” 1st Conference on Constraint-based Reconstruction and Analysis held June 24th-26th in Reykjavik, Iceland, 6/2011.

Lavanya Babujee (2009-2016). Lavanya began working in my lab as a postdoctoral researcher and has since been promoted to Assistant Scientist. She focuses on analyzing evolution of genome content and regulatory variation of primarily, though not

22 exclusively, plant pathogenic enterobacteria (1 joint first-author publication, 1 submitted, 1 in preparation).

Venkatesh Balakrishnan (2008-2011). Venkat sequenced the genomes of eight soft rot associated plant pathogens to discover plant cell wall degrading enzymes that may have bioengineering applications (1 co-authored publication in preparation). Upon completion of our Great Lakes Bioenergy Research Center project, he remained in an honorary appointment and made significant contributions to a cross-species comparison of the anaerobic stimulons of enterobacteria using microarrays (1 co-authored publication). He is currently employed by DNASTAR in Madison, WI, a company that engineers software for life science research.

Bradley Anderson (2005-2009). Brad originally joined the lab with a 1 year postdoctoral fellowship from the Genome Sciences Training Program (GSTP) during which he developed a novel approach and corresponding software (CGHScan) to detect copy number differences from tiled microarray hybridizations of genomic DNA (1 publication). Subsequently, he was hired as an Assistant Scientist and worked as an ERIC-BRC genome database curator specializing in annotation of non-ribosomal peptide synthesis systems, small RNAs and application of GO terms to genes involved with virulence (4 co-authored publications). Brad is currently employed as a publications editor in the laboratory of R. Anderson (UW-Madison Dept. of Medicine).

Yu Qiu (2007). Yu spent approximately 6 months as a short-term postdoc following completion of his Ph.D. at UW-Madison. He focused on integration of diverse microarray datasets for Salmonella and E. coli from other public resources into a unified interface provided through the ERIC-BRC (2 co-authored publications). He subsequently was a postdoctoral researcher with Bernard Pahlsson (UC San Diego) and is currently employed in the laboratory of Andy Minn (University of Pennsylvania).

Jon Boyle (2003). Jon worked in my group for 6 months to gain experience in genome- scale analysis. He annotated ESTs as part a collaborative project to characterize the transcriptome of immune-activated mosquitos (1 co-authored publication). He went on to do a second postdoc with John Boothroyd (Stanford University) and is currently an Assistant Professor in the Department of Biology at the University of Pittsburgh.

Graduate students

Anna Rissman (Genetics, 2011-2012). Anna is studying the evolution of metabolic and regulatory networks associated with energy metabolism. She previously was an undergraduate researcher in my group focused on developing a method to reorder contigs from draft genomes based on alignment to a reference genome and implementing it as part of our Mauve genome alignment software (1 publication). She was awarded a

23 Hilldale Scholarship and was the first undergraduate at UW-Madison to obtain a B.S. in bioinformatics through an individually crafted degree program. She also conducted analyses that factored into characterization of the Pectobacterium pan-genome and the ERIC-BRC database (2 co-authored publications). Anna is on leave.

Bryan Biehl (Comparative Biomedical Sciences, 2004-2014). Bryan is investigating the evolution of phytopathogenic enterobacteria using comparative genomics and constraint-based genome-scale metabolic modeling (manuscript in prep). He also developed new Gene Ontology terms for structured annotation of genes involved with plant-microbe interactions (1 co-authored publication) and made substantial contributions to annotation of plant pathogens (5 co-authored publications) and other enterobacterial genomes (2 co-authored publications). Invited Presentations “Examining the Root of Plant Disease Using Metabolic Models of Plant Pathogens”. American Society for Microbiology Annual Meeting, San Francisco, CA, 6/2012. This talk was one of five selected by the community at large in an online contest.

Jennifer Apodaca (Ph.D., Microbiology Doctoral Training Program, 2005-2013). Jen is characterizing variation in the transcriptional response to oxygen among enterobacteria (1 joint first author publication, 1 in preparation) and evolution of the oxygen-responsive regulatory network among E. coli strains. She obtained a Genome Sciences Training Program fellowship. Currently, Jen is a teaching fellow at University of Texas – El Paso.

Bing Ma (Ph.D. Computational Biology, 2006-2011). Bing’s thesis had two major foci. One was to build a robust genome-scale phylogenetic framework for enterobacteria that both captured the dominant phylogenetic signal and characterized the uncertainty that arises from methodological artifacts and horizontal gene transfer (1 publication, 2 co- authored, 1 in preparation). The second was to develop a machine learning approach to identify genes involved with host-microbe interaction (1 manuscript in preparation). She obtained one of the few CIBM/WID fellowships available for non-domestic students. Bing is currently a postdoctoral fellow working on metagenomics with Jacques Ravel at the University of Maryland (Institute of Genomic Sciences).

Michael Gilson (M.S. Comparative Biomedical Sciences, 2006-2010). Mike characterized the evolution of large family of chemotaxis signaling proteins discovering parallel expansion of the number and diversity of receptors in two distinct lineages of plant-associated enterobacteria. Mike also worked with me as an undergraduate (Computer Sciences) and made significant contributions to our software and database infrastructure (3 co-authored publications). Mike is currently employed as a programmer at the Ohio State University.

Aaron Darling (Ph.D. Computational Biology, 2000-2006). Aaron was the primary developer of our Mauve genome alignment software (4 publications). This software is

24 used extensively by the microbial genomics research community and these publications have collectively generated over 700 citations. He obtained a CIBM fellowship and was selected as the UW-Madison representative to speak at the annual meeting of all NLM training programs. He won a Best Poster Award at the 2002 Annual International Conference on Intelligent Systems for Molecular Biology (Edmonton, Canada) and an Orion MultiSystems “Personal Supercomputing Contest”. He contributed to a variety of other projects in my group (6 publications). He was awarded an NSF Postdoctoral Fellowship to work on evolutionary genomics of bacteria with Mark Ragan at the University of Queensland and subsequently Jonathan Eisen at UC Davis. Aaron is currently an Associate Professor at the University of Technology, Sydney.

Michael Hibbing (M.S. Veterinary Sciences 2003-2005). Mike conducted a multilocus phylogenetic analysis of soft rot-associated enterobacteria and compiled an inventory of all documented plant hosts infected with either Pectobacterium or Dickeya species revealing that together, these two genera are pathogens of species from 50% of angiosperm plant orders. (1 joint first-author publication). Mike completed a Ph.D. in the laboratory of Clay Fuqua at Indiana University Bloomington studying quorum sensing in Agrobacterium. He is now a postdoctoral researcher with Scott Hultgren at Washington University – St. Louis.

Other Doctoral Thesis Committees (2014-present): Drew Doering, Cellular and Molecular Biology Christina Kuang, Cellular and Molecular Biology Katiria Rivera, Biophysics Andrew Hasley, Genetics 2016 Martin Bontrager, Genetics 2016 Kurt Elhert, Genetics 2015 (M.S.) Seth Keel, Genetics 2015 (M.S.) Dvorka Guilisa, Genetics 2014 Pallab Ghosh, Comparative Biomedical Sciences 2014 Saheed Imam, Cellular and Molecular Biology 2014

Research Interns Jon Matteson (2015). Jon completed his B.S. in Biology-Evolution Option in December 2015 and continues his work on identifying the presence of understudied enterobacteria in the human microbiome.

Kelsey Johnson (2012). Kelsey completed her B.S. in Genetics in May 2012 and joined my lab late in her final semester to gain experience in genomics and phylogenetic analysis. She analyzed the role of horizontal gene transfer in the evolution of hydrogenases, key enzymes for anaerobic respiration and fermentation.

25 Roman Peplinski (2010-2011). Roman graduated with a B.S. in Medical Microbiology and Immunology and continued his research training by working closely with postdoctoral fellow Dave Baumler to develop genome-scale metabolic models of pathogenic E. coli and Shigella (1 co-authored publication). He is currently in medical school at UW-Madison.

Undergraduates Samantha Robertson, Genetics (2014-present) Jonathan Matteson, Biology-Evolution Option (2014-2015) Alexander Sobin, Biology (2012-2015) Andrew Tritt, Genetics (2008-2010) at Joint Genome Institutes, Walnut Creek, CA Ashley Bates, Genetics (2010) *Roman Peplinski, Medical Microbiology and Immunology (2010) *Anna Rissman, Bioinformatics (2007-2009) Sarah Worzella, Biomedical Engineering (2005-2008) Akansha Bhargava, Genetics (2006) John Simpkin, Biochemistry (2004) Bio 152 Mentored Research for 7 student team: Ioana Baiu, Aisha Harun, Brian Bluell, Sara Worzella, Caitlin Flaherty, Rebecca Johnson, Aydin Beseli (2005) Kari Williams (2004-2005) Eric Brugger, Biology (2004) Maggie Bach, Genetics (2003-2004) *Michael Rusch, Computer Sciences (2002- 2003) *Michael Gilson, Computer Sciences (2002- 2004) *Michael Hibbing, Medical Microbiology and Immunology (2001-2003) *Aaron Darling, Computer Sciences (2000) Lena Ho Wai Mun, Biochemistry, Honors (2001) Melinda Spang, Medical Microbiology and Immunology (2000-2002) Brian Gettler, Computer Sciences (1998-2001)

*Continued in my laboratory after undergraduate research experience, detailed above

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