DOCSLIB.ORG

Annual Report 2017

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Annual Report 2017 Annual Report 2017 Biocenter Finland – Annual Report 2015-2016 Biocenter Finland Annual Report 2017 Editor: Antti Siltanen Acknowledgements: We thank the technology platform chairs and BF board members for cooperation in compiling this report. www.biocenter.fi Biocenter Finland – Annual Report 2017 2 CONTENTS FOREWORD ............................................................................................................................................... 4 STATISTICS ............................................................................................................................................... 5 HOST UNIVERSITIES, MEMBER INSTITUTES AND FACULTY .......................................................... 7 GOVERNANCE AND ORGANIZATION .................................................................................................. 9 SCIENTIFIC SUCCESS STORIES............................................................................................................ 11 BIOCENTER FINLAND TECHNOLOGY PLATFORMS ........................................................................ 20 BIOINFORMATICS .............................................................................................................................. 21 BIOLOGICAL IMAGING ..................................................................................................................... 24 GENOME-WIDE METHODS ................................................................................................................ 33 MODEL ORGANISMS .......................................................................................................................... 37 PROTEOMICS AND METABOLOMICS .............................................................................................. 42 STEM CELLS AND BIOMATERIALS ................................................................................................. 49 STRUCTURAL BIOLOGY ................................................................................................................... 53 TRANSLATIONAL TECHNOLOGIES ................................................................................................. 59 VIRAL GENE TRANSFER & CELL THERAPY .................................................................................. 65 NEW PLATFORMS .............................................................................................................................. 68 CONTACT INFORMATION .................................................................................................................... 73 Biocenter Finland – Annual Report 2017 3 FOREWORD The mission of Biocenter Finland is to support where BF is positioned as a major national frontier research in the life sciences by providing infrastructure. The criteria of the interim assessment open access technology platforms and services. BF included the level of development, impact and operates as a nation-wide research infrastructure, significance, as well as openness and collaborative which is distributed to the five Finnish biocenters. use of the research infrastructure. BF was placed in The biocenters and BF are hosted by University of the most advanced category, which is a testimony of Eastern Finland, University of Helsinki, University the success of the BF concept and the quality of the of Oulu, University of Tampere, University of operations. Turku and Åbo Akademi University. BF Since 2017, BF works in close collaboration with establishes, develops and coordinates state-of-the- the Finnish nodes of the Health and Food domain of art technology services and ensures resources for the European infrastructure Projects (ESFRI). The investments into the facilities. The personnel costs Finnish ESFRI nodes are BBMRI (biobanking), are financed by the host universities. More than EATRIS (translational medicine), ELIXIR 2000 research groups in universities, research (bioinformatics), EU-OPENSCREEN (drug institutes and companies in Finland and abroad use screening), EuroBioImaging, Infrafrontier (mouse the BF technology services annually. models) and Instruct-FI (structural biology). The well-established nine technology platforms of Not only ESFRI memberships provide access for BF, Bioinformatics, Biological Imaging, Genome- the Finnish life scientists to research infrastructures wide Methods, Model Organisms, Proteomics and not available at home. Finland is also member of the Metabolomics, Stem Cells and Biomaterials, European Molecular Biology laboratory EMBL and Structural Biology, Translational Technologies and the European Molecular Biology Conference Viral Gene Transfer & Cell Therapy, will be EMBC, but the memberships are not taken fully complemented with three new ones, Genome advantage of. BF is committed to promote to the Editing, Liquid Biopsies and Single-cell Omics. Finnish life scientists’ community the use of the The establishment of the new platforms has begun core facilities and collaboration opportunities that in 2017 with resources that BF obtained from the EMBL offers. EMBC provides funds to the competitive Research Infrastructure Programme of European Molecular Biology Organization EMBO the Academy of Finland (the Finnish Research which offers short and long-term fellowships for Council). young researchers and organizes courses, In 2017, the host universities made new investments workshops, training and conferences. Raising the of about 5 M€, mainly to the Genome-wide awareness of EMBL and EMBC/EMBO started in methods and to the newly established Single-cell 2017 with a BF-workshop for PhD candidates and omics platforms. The universities’ salary support post-docs to showcase what EMBC/EMBO can remained at the 2016 level. offer to support their careers. The choice of the platforms to be established or up- graded is crucial. New platforms must support renewal of science, conform to the needs of established scientists as well as the new generation of researchers, and support implementation of the research strategies of BF’s host universities. Therefore, BF consulted frontier life scientists such as the directors of Centers of Excellence, Academy professors and ERC Starting Grantees on their needs. The choices were consolidated by BF’s Board, where all of its host universities are represented. The year 2017 was marked by an international mid- term evaluation of the Finnish Research Professor Marja Makarow Infrastructure Strategy and Roadmap 2014-2020, Director of Biocenter Finland Biocenter Finland – Annual Report 2017 4 STATISTICS Technology platform funding €40M €30M Figure 1. BF technology platform €20M funding broken down to direct salary support from the host universities, other host university funding, cost recovery from user fees, and other €10M funding sources. The increased other financial support from the host universities was mainly due to increased investments to the Genome-wide methods platform 2017 2016 2015 (4M€), and the new Single-cell Other funding omics platform (1M€). User fees Other financial support from the host universities Direct funding from the host universities to BF platforms Bioinformatics technology platform Electron microscopy Light microscopy Small animal molecular imaging (SPECT/CT) of the RTI unit Genome-wide methods FinnMouse National infrastr. for research on non-mammalian model organisms Protein-proteome platform Metabolomics platform Stem cells and biomaterials Structural biology Protein service for biophysical and structural characterization Biobank technologies Drug discovery and chemical biology Viral gene transfer Single-cell omics Genome editing liquid biopsies Figure 2. Distribution of direct host university funding to BF technology platforms in 2017. Biocenter Finland – Annual Report 2017 5 Users 3000 2250 1500 750 Number of usergroups Figure 3. Number of research groups and non-academic customers 2017 2016 2015 using BF technology platform Local National International Non-academic Total services. Technology platform personnel 160 160 120 120 80 80 equivalents) equivalents) 40 40 Platform personnel (full-time Platform personnel (full-time 2017 2016 2015 2017 2016 2015 Other funding Technicians PhD students Postdoctoral researchers Direct funding from the host universities to BF platforms Senior scientists Figure 4. BF technology platform personnel in Figure 5. BF technology platform personnel by full-time equivalents broken down by source of career stage. funding. Biocenter Finland – Annual Report 2017 6 HOST UNIVERSITIES, MEMBER INSTITUTES AND FACULTY Host universities and member institutes BF is a distributed national research infrastructure Helsinki. HiLIFE includes Institute of that in 2017 consisted of five member institutes Biotechnology and Institute for Molecular Medicine hosted by six universities (Fig. 6). The directors of Finland FIMM as operational units. At University each institute serve as the Governing Board of BF. of Tampere, the Faculty of Medicine and Life Sciences replaced BioMediTech as the member From 2017 on, Helsinki Institute of Life Science institute from the beginning of 2017. HiLIFE is the member institute at the University of Figure 6. The host universities and their BF member institutes in 2017. Faculty At the end of 2017, the Biocenter Finland Faculty J, Jolkkonen J, Jurvelin J, Jänis J, Kaarniranta K, comprised of 413 principal investigators listed Kinnunen T, Koistinaho J, Koistinen A, Korhonen below. Each member institute has used its own R, Kosma VM, Kröger H, Laakso M, Lehto VP, criteria and/or peer review process in
Load more

Recommended publications
  • Methodology for Predicting Semantic Annotations of Protein Sequences by Feature Extraction Derived of Statistical Contact Potentials and Continuous Wavelet Transform
    Universidad Nacional de Colombia Sede Manizales Master’s Thesis Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform Author: Supervisor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez A thesis submitted in fulfillment of the requirements for the degree of Master’s on Engineering - Industrial Automation in the Department of Electronic, Electric Engineering and Computation Signal Processing and Recognition Group June 2014 Universidad Nacional de Colombia Sede Manizales Tesis de Maestr´ıa Metodolog´ıapara predecir la anotaci´on sem´antica de prote´ınaspor medio de extracci´on de caracter´ısticas derivadas de potenciales de contacto y transformada wavelet continua Autor: Tutor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez Tesis presentada en cumplimiento a los requerimientos necesarios para obtener el grado de Maestr´ıaen Ingenier´ıaen Automatizaci´onIndustrial en el Departamento de Ingenier´ıaEl´ectrica,Electr´onicay Computaci´on Grupo de Procesamiento Digital de Senales Enero 2014 UNIVERSIDAD NACIONAL DE COLOMBIA Abstract Faculty of Engineering and Architecture Department of Electronic, Electric Engineering and Computation Master’s on Engineering - Industrial Automation Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform by Gustavo Alonso Arango Argoty In this thesis, a method to predict semantic annotations of the proteins from its primary structure is proposed. The main contribution of this thesis lies in the implementation of a novel protein feature representation, which makes use of the pairwise statistical contact potentials describing the protein interactions and geometry at the atomic level.
    [Show full text]
  • EMBO Encounters Issue43.Pdf
    WINTER 2019/2020 ISSUE 43 Nine group leaders selected Meet the first EMBO Global Investigators PAGE 6 Accelerating scientific publishing EMBO publishing costs Review Commons Making our journals’ platform announced finances public PAGE 3 PAGES 10 – 11 Welcome, Young Investigators! Contract replaces stipend Marking ten years 27 group leaders join the programme EMBO Postdoctoral Fellowships EMBO Molecular Medicine receive an update celebrates anniversary PAGES 4 – 5 PAGE 7 PAGE 13 www.embo.org TABLE OF CONTENTS EMBO NEWS EMBO news Review Commons: accelerating publishing Page 3 EMBO Molecular Medicine turns ten © Marietta Schupp, EMBL Photolab Marietta Schupp, © Page 13 Editorial MBO was founded by scientists for Introducing 27 new Young Investigators scientists. This philosophy remains at Pages 4-5 Ethe heart of our organization until today. EMBO Members are vital in the running of our Meet the first EMBO Global programmes and activities: they screen appli- Accelerating scientific publishing 17 journals on board Investigators cations, interview candidates, decide on fund- Review Commons will manage the transfer of ing, and provide strategic direction. On pages EMBO and ASAPbio announced pre-journal portable review platform the manuscript, reviews, and responses to affili- Page 6 8-9 four members describe why they chose to ate journals. A consortium of seventeen journals New members meet in Heidelberg dedicate their time to an EMBO Committee across six publishers (see box) have joined the Fellowships: from stipends to contracts Pages 14 – 15 and what they took away from the experience. n December 2019, EMBO, in partnership with decide to submit their work to a journal, it will project by committing to use the Review Commons Page 7 When EMBO was created, the focus lay ASAPbio, launched Review Commons, a multi- allow editors to make efficient editorial decisions referee reports for their independent editorial deci- specifically on fostering cross-border inter- Ipublisher partnership which aims to stream- based on existing referee comments.
    [Show full text]
  • Refining Neural Network Predictions for Helical Transmembraneproteins by Dynamic Programming
    From: ISMB-96 Proceedings. Copyright © 1996, AAAI (www.aaai.org). All rights reserved. Refining neural network predictions for helical transmembraneproteins by dynamic programming BurkhardRost 0, Rita Casadio, and Piero Fariselli EMBL,69012 Heidelberg, Germany Lab. of Biophysics, Dep. of Biology EBI, Hinxton, Cambridge CB101RQ, U.K. Univ. of Bologna, 40126 Bologna, Italy Rost @embl-heidelberg.de Casadio @kaiser.alma.unibo.it Abstract time. Currently, the gap between the number of known For transmembrane proteins experimental determina- protein sequences and protein three-dimensional (3D) tion of three-dimensional structure is problematic. structures is still increasing (Rost 1995). However, However, membraneproteins have important impact experimental structure determination is becomingmore of for molecular biology in general, and for drug design a routine (Lattman 1994). Thus, within the next decades in particular. Thus, prediction method are needed. we may know the three-dimensional (3D) structure for Here we introduce a method that started from the most proteins. Even in such an optimistic scenario, output of the profile-based neural network system experimental information is likely to remain scarce for PHDhtm(Rost, et al. 1995). Instead of choosing the integral membraneproteins. These challenge experimental neural network output unit with maximalvalue as pre- structure determination: X-ray crystallography is diction, we implemented a dynamic programming-like problematic as the hydrophobic molecules hardly refinement procedure that aimed at producing the best crystallise; and for nuclear magnetic resonance (NMR) model for all transmembranehelices compatible with spectroscopy transmembraneproteins are usually too long. the neural network output. The refined prediction was Today, 3D structure is known for only six membrane used successfully to predict transmembranetopology proteins (Rost, et al.
    [Show full text]
  • A Day in the Life of Dr K. Or How I Learned to Stop Worrying and Love Lysozyme: a Tragedy in Six Acts Gunnar Von Heijne
    Article No. jmbi.1999.2998 available online at http://www.idealibrary.com on J. Mol. Biol. (1999) 293, 367±379 A Day in the Life of Dr K. or How I Learned to Stop Worrying and Love Lysozyme: A Tragedy in Six Acts Gunnar von Heijne Department of Biochemistry About the play: In modern drama, the agonizing nature of membrane Stockholm University, S-106 91 protein work has not been adequately acknowledged. It is perhaps sig- Stockholm, Sweden ni®cant that the ®rst attempt to bring this darker aspect of human exist- ence into focus comes from a Scandinavian author, writing in the tradition of Ibsen and Strindberg but with a distinctly turn-of-the-millen- ium approach to the inner life of his characters: the despairing Dr K; the cynical Dr R with his post-modernistic life credo; the ambitious but unfeeling Dr C; the modern UÈ bermensch, Dr B., with his almost Nietzschean view of human nature. This is a play that is brutally honest, yet full of empathy for the poor souls that get caught between the Scylla of unreachable scienti®c glory and the Charybdis of helpless mediocrity. James Glib-Burdock, drama critic for The Stratford Observer. # 1999 Academic Press Keywords: membrane protein; modern tragedy The Cast Dr K., a middle-aged biochemist with a certain interest in membrane proteins. Dr R., another middle-aged biochemist with other things on his mind. Dr C., a young, hungry crystallographer. Dr B., a bioinformatics guru. Dr H., over in molecular biology. A class of medical school students. Act I Wherein Dr K.
    [Show full text]
  • I S C B N E W S L E T T
    ISCB NEWSLETTER FOCUS ISSUE {contents} President’s Letter 2 Member Involvement Encouraged Register for ISMB 2002 3 Registration and Tutorial Update Host ISMB 2004 or 2005 3 David Baker 4 2002 Overton Prize Recipient Overton Endowment 4 ISMB 2002 Committees 4 ISMB 2002 Opportunities 5 Sponsor and Exhibitor Benefits Best Paper Award by SGI 5 ISMB 2002 SIGs 6 New Program for 2002 ISMB Goes Down Under 7 Planning Underway for 2003 Hot Jobs! Top Companies! 8 ISMB 2002 Job Fair ISCB Board Nominations 8 Bioinformatics Pioneers 9 ISMB 2002 Keynote Speakers Invited Editorial 10 Anna Tramontano: Bioinformatics in Europe Software Recommendations11 ISCB Software Statement volume 5. issue 2. summer 2002 Community Development 12 ISCB’s Regional Affiliates Program ISCB Staff Introduction 12 Fellowship Recipients 13 Awardees at RECOMB 2002 Events and Opportunities 14 Bioinformatics events world wide INTERNATIONAL SOCIETY FOR COMPUTATIONAL BIOLOGY A NOTE FROM ISCB PRESIDENT This newsletter is packed with information on development and dissemination of bioinfor- the ISMB2002 conference. With over 200 matics. Issues arise from recommendations paper submissions and over 500 poster submis- made by the Society’s committees, Board of sions, the conference promises to be a scientific Directors, and membership at large. Important feast. On behalf of the ISCB’s Directors, staff, issues are defined as motions and are discussed EXECUTIVE COMMITTEE and membership, I would like to thank the by the Board of Directors on a bi-monthly Philip E. Bourne, Ph.D., President organizing committee, local organizing com- teleconference. Motions that pass are enacted Michael Gribskov, Ph.D., mittee, and program committee for their hard by the Executive Committee which also serves Vice President work preparing for the conference.
    [Show full text]
  • Glycoprotein Hormone Receptors in Sea Lamprey
    University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Fall 2007 Glycoprotein hormone receptors in sea lamprey (Petromyzon marinus): Identification, characterization and implications for the evolution of the vertebrate hypothalamic-pituitary-gonadal/thyroid axes Mihael Freamat University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Freamat, Mihael, "Glycoprotein hormone receptors in sea lamprey (Petromyzon marinus): Identification, characterization and implications for the evolution of the vertebrate hypothalamic-pituitary-gonadal/ thyroid axes" (2007). Doctoral Dissertations. 395. https://scholars.unh.edu/dissertation/395 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. GLYCOPROTEIN HORMONE RECEPTORS IN SEA LAMPREY (PETROMYZON MARI Nil S): IDENTIFICATION, CHARACTERIZATION AND IMPLICATIONS FOR THE EVOLUTION OF THE VERTEBRATE HYPOTHALAMIC-PITUITARY-GONADAL/THYROID AXES BY MIHAEL FREAMAT B.S. University of Bucharest, 1995 DISSERTATION Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy In Biochemistry September, 2007 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3277139 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted.
    [Show full text]
  • Downloaded from Genbank, with Accession Numbers Found in Table 1
    bioRxiv preprint doi: https://doi.org/10.1101/030619; this version posted November 4, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Common and phylogenetically widespread coding for peptides by bacterial small RNAs Robin C. Friedmana,b, Stefan Kalkhofc,d, Olivia Doppelt-Azerouale, Stephan Muellerc, Martina Chovancov´ac, Martin von Bergenc,f,g, Benno Schwikowskia a Systems Biology Laboratory, Institut Pasteur, Paris, France b Molecular Microbial Pathogenesis Unit, Institut Pasteur, Paris, France c Department of Proteomics, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany d Current Address: Department of Bioanalytics, University of Applied Sciences and Arts of Coburg, Coburg, Germany e Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France f Department of Metabolomics, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany g Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark November 4, 2015 Abstract While eukaryotic noncoding RNAs have recently received intense scrutiny, it is becoming clear that bacterial transcription is at least as pervasive. Bacterial small RNAs and antisense RNAs (sRNAs) are often assumed to be noncoding, due to their lack of long open reading frames (ORFs). However, there are numerous examples of sRNAs encoding for small proteins, whether or not they also have a regulatory role at the RNA level. Here, we apply flexible machine learning techniques based on sequence features and comparative genomics to quantify the prevalence of sRNA ORFs under natural selection to maintain protein-coding function in phylogenetically diverse bacteria.
    [Show full text]
  • Topology Prediction of Α-Helical Transmembrane Proteins – Christoph Peters
    Topology Prediction of a-Helical Transmembrane Proteins – Christoph Peters Topology Prediction of a-Helical Transmembrane Proteins Christoph Peters Abstract Membrane proteins fulfil a number of tasks in cells, including signalling, cell-cell in- teraction, and the transportation of molecules. The prominence of these tasks makes membrane proteins an important target for clinical drugs. Because of the decreas- ing price of sequencing, the number of sequences known is increasing at such a rate that manual annotations cannot compete. Here, topology prediction is a way to pro- vide additional information. It predicts the location and number of transmembrane helices in the protein and the orientation inside the membrane. An important factor to detect transmembrane helices is their hydrophobicity, which can be calculated using dedicated scales. In the first paper, we studied the difference between several hy- drophobicity scales and evaluated their performance. We show that while they appear to be similar, their performance for topology prediction differs significantly. The bet- ter performing scales appear to measure the probability of amino acids being within a transmembrane helix, instead of just being located in a hydrophobic environment. Around 20% of the transmembrane helices are too hydrophilic to explain their insertion with hydrophobicity alone. These are referred to as marginally hydrophobic helices. In the second paper, we studied three of these helices experimentally and performed an analysis on membrane proteins. The experiments show that for all three helices positive charges on the N-terminal side of the subsequent helix are important to insert, but only two need the subsequent helix. Additionally, the analysis shows that not only the N-terminal helices are more hydrophobic, but also the C-terminal transmembrane helices.
    [Show full text]
  • Approaches to Efficient Multiple Sequence Alignment And
    Approaches to Efficient Multiple Sequence Alignment and Protein Search Adrienn Szab´o Supervisor: Istv´anMikl´os E¨otv¨os Lor´and University, Budapest Faculty of Informatics PhD School of Computer Science Erzs´ebet Csuhaj-Varj´u,D.Sc. PhD Program of ”Basics and methodology of informatics” J´anosDemetrovics, D.Sc. A dissertation submitted for the degree of PhilosophiæDoctor (PhD) 2016 ii Acknowledgements Firstly, I would like to thank the extensive help and guidance of my supervisors, Istv´anMikl´os and Andr´asA. Bencz´ur . I would also like to express my gratitude to M´aty´asBachorecz and N´ora Juh´asz , who helped tremendously in developing, coding and testing the software packages of Chapter 5. Lastly, I list here all my friends and colleagues at MTA SZTAKI, who contributed to the final version of this thesis by pointing out several typos and mistakes: Akos´ Csaba, D´avidBalamb´er, Tam´as Kiss, J´uliaPap, D´avidSikl´osi,P´eterSzab´o. ii Contents 1 Introduction 1 1.1 Datamining................................ 2 1.2 Bioinformatics .............................. 3 2 Sequence alignment methods 5 2.1 Theory and practice of sequence alignment . 6 2.2 Cornercuttingmethods. 32 2.3 Progressivealignment .......................... 35 2.4 SoftwaretoolsforMSA ......................... 38 2.5 Handlingalignmentuncertainty . 41 2.6 Introductiontoproteinsearchmethods . 43 3 Reticular Alignment 47 3.1 Introduction................................ 47 3.2 Methods .................................. 50 3.3 Resultsanddiscussion.......................... 59 3.4 Implementation details and authors’ contributions . ...... 65 4 Efficient representation of uncertainty in MSA 69 4.1 Introduction................................ 69 4.2 Methods .................................. 70 iii CONTENTS 4.3 Implementation details and measurements . 74 4.4 Resultsandconclusions ......................... 79 5 Protein Search 83 5.1 Background ...............................
    [Show full text]
  • Structure and Topology Around the Cleavage Site Regulate Post
    RESEARCH ARTICLE Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide Erik Lee Snapp1†, Nicholas McCaul2†, Matthias Quandte2‡, Zuzana Cabartova3, Ilja Bontjer4, Carolina Ka¨ llgren5,6, IngMarie Nilsson5,6, Aafke Land2§, Gunnar von Heijne5,6, Rogier W Sanders4, Ineke Braakman2* 1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; 2Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands; 3National Institute of Public Health, National Reference Laboratory for Viral Hepatitis, Prague, Czech Republic; 4Department of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands; 5Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden; 6Science for Life Laboratory, Stockholm University, Solna, Sweden *For correspondence: Abstract Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is targeted to [email protected] the endoplasmic reticulum (ER) by its signal peptide during synthesis. Proper gp160 folding in the †These authors contributed ER requires core glycosylation, disulfide-bond formation and proline isomerization. Signal-peptide equally to this work cleavage occurs only late after gp160 chain termination and is dependent on folding of the soluble Present address: ‡dr heinekamp subunit gp120 to a near-native conformation. We here detail the mechanism by which co- Benelux BV, Riethoven, translational signal-peptide cleavage is prevented. Conserved residues from the signal peptide and Netherlands; §Hogeschool residues downstream of the canonical cleavage site form an extended alpha-helix in the ER Utrecht, Institute of Life membrane, which covers the cleavage site, thus preventing cleavage.
    [Show full text]
  • CV Burkhard Rost
    Burkhard Rost CV BURKHARD ROST TUM Informatics/Bioinformatics i12 Boltzmannstrasse 3 (Rm 01.09.052) 85748 Garching/München, Germany & Dept. Biochemistry & Molecular Biophysics Columbia University New York, USA Email [email protected] Tel +49-89-289-17-811 Photo: © Eckert & Heddergott, TUM Web www.rostlab.org Fax +49-89-289-19-414 Document: CV Burkhard Rost TU München Affiliation: Columbia University TOC: • Tabulated curriculum vitae • Grants • List of publications Highlights by numbers: • 186 invited talks in 29 countries (incl. TedX) • 250 publications (187 peer-review, 168 first/last author) • Google Scholar 2016/01: 30,502 citations, h-index=80, i10=179 • PredictProtein 1st Internet server in mol. biol. (since 1992) • 8 years ISCB President (International Society for Computational Biology) • 143 trained (29% female, 50% foreigners from 32 nations on 6 continents) Brief narrative: Burkhard Rost obtained his doctoral degree (Dr. rer. nat.) from the Univ. of Heidelberg (Germany) in the field of theoretical physics. He began his research working on the thermo-dynamical properties of spin glasses and brain-like artificial neural networks. A short project on peace/arms control research sketched a simple, non-intrusive sensor networks to monitor aircraft (1988-1990). He entered the field of molecular biology at the European Molecular Biology Laboratory (EMBL, Heidelberg, Germany, 1990-1995), spent a year at the European Bioinformatics Institute (EBI, Hinxton, Cambridgshire, England, 1995), returned to the EMBL (1996-1998), joined the company LION Biosciences for a brief interim (1998), became faculty in the Medical School of Columbia University in 1998, and joined the TUM Munich to become an Alexander von Humboldt professor in 2009.
    [Show full text]
  • Experimentally Based Topology Models for E. Coli Inner Membrane Proteins
    Experimentally based topology models for E. coli inner membrane proteins MIKAELA RAPP,1 DAVID DREW,1 DANIEL O. DALEY,1 JOHAN NILSSON,2,3 1,2 1,2 1 TIAGO CARVALHO, KARIN MELÉN, JAN-WILLEM DE GIER, AND GUNNAR VON HEIJNE1,2 1Department of Biochemistry and Biophysics, and 2Stockholm Bioinformatics Center, Stockholm University, Stockholm, Sweden 3Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (RECEIVED December 8, 2003; FINAL REVISION January 9, 2004; ACCEPTED January 9, 2004) Abstract Membrane protein topology predictions can be markedly improved by the inclusion of even very limited experimental information. We have recently introduced an approach for the production of reliable topology models based on a combination of experimental determination of the location (cytoplasmic or periplasmic) of a protein’s C terminus and topology prediction. Here, we show that determination of the location of a protein’s C terminus, rather than some internal loop, is the best strategy for large-scale topology mapping studies. We further report experimentally based topology models for 31 Escherichia coli inner membrane proteins, using methodology suitable for genome-scale studies. Keywords: membrane proteins; topology; prediction; bioinformatics; fusion protein; PhoA; green fluores- cent protein; GFP Supplemental material: see www.proteinscience.org The topology of an integral membrane protein—that is, a ogy prediction methods can be substantially improved by specification of the membrane-spanning segments of the the inclusion of limited experimental information such as polypeptide chain and their in/out orientation relative to the the location of the N- or C-terminal end of the protein membrane—is a basic characteristic that helps guide experi- relative to the membrane (Drew et al.
    [Show full text]