IMBIMs årsbok 2010
172 Pages
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IMBIMs årsbok 2010


Downloading requires you to have access to the YouScribe library
Learn all about the services we offer
172 Pages


Anna-Maja Nyström, post-doc (associated with Department of Animal ..... university, INRA (France) and Virginia Polytechnic Institute (Blacksburg, ..... Patricio Rivera, graduate student*/postdoc§ ...... Check our web page for updates: ...... vpr mRNA by inhibiting the 5'- splice site of exon 3.



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INTRODUCTION Research at the Department of Medical Biochemistry and Microbiology (IMBIM) is pursued within the three major areas of genomics, biochemistry and molecular cell biology and microbiology. This categorization has a historical and organizational background, with numerous active scientific exchanges and collaborations between the three sections. In addition, much of the research is interdisciplinary in character and involves collaboration with other departments at Uppsala University and other universities. Core facilities for proteomics and transgenic animals are present at IMBIM, which also hosts the administrative functions and offices of the director of Science for Life Laboratory in Uppsala (SciLifeLab-U).  Over the last decade, IMBIM has been transformed greatly, with the enrollment of strong groups in genomics and bacteriology. Furthermore, scientists in the area of basic immunology have joined IMBIM. At the same time, research constellations consisting of several, often smaller, research groups have been formed, and have the strength to conduct internationally competitive research. The SciLifeLab-U initiative has created possibilities for broader contacts between scientists at IMBIM and other departments at the university. Several new projects have been instigated as a result of this. During 2010, the potential impact of SciLifeLab-U on research at IMBIM has become increasingly evident.  2010 has been a successful and dynamic year for IMBIM. Several new research groups headed by younger principal investigators have been formed. These new groups are the result of an organic growth of the respective science sections at IMBIM, strengthening and complementing already existing research milieus. Three younger scientists at IMBIM have been granted research positions from governmental research councils during 2010 in the face of strong competition. Dr.Maria Ringvallreceived funds for a four-year position as assistant professor from the Swedish Research Council (VR), while Dr.Patric Jernand Dr. Gerli Rosengren-Pielbergwon support for similar positions from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS). IMBIM congratulates these three scientists and looks forward to their continuing success. Furthermore, 2010 saw the finalization of the process to recruit a new professor in molecular bacteriology. IMBIM is happy to welcome ProfessorDiarmaid Hughesto this chair. Professor Hughes will further strengthen research and teaching at the microbiology section at IMBIM and add to the very strong and urgent research program in antibiotic resistance. Finally, Dr. Aristidis Moustakasjoined IMBIM in July 2010 after having received a prestigious award from the Swedish Cancer Society for six years as a senior researcher. He maintains his position of deputy director at the Ludwig Institute for Cancer Research in Uppsala (LICR). He will transfer a sizeable portion of his research and teaching activities to IMBIM, where he is tenured.  Two active professors left IMBIM in 2010 to move to other universities better suited to their specific programs. ProfessorHans Ronnemoved to the Swedish University of Agricultural Sciences and ProfessorStefan Schwartzmoved to Lund University. IMBIM extends its thanks to these two scientists for their valuable contributions and wishes them all future success.
 Publications in international peer-reviewed scientific journals constitute an important measure of production for any science department. In 2010, scientists at IMBIM published almost one hundred articles. Around ten of these were reviews or book chapters and the remainders were original reports, published in international scientific journals, with several appearing in some of the most prestigious journals in the world. Measured in these terms, therefore, production at IMBIM is substantial and the standard of research is of the very highest quality; a bibliometric survey conducted in 2010, documenting citations of work published by IMBIM scientists from the year 2000 and onwards. The results of the survey showed a very positive trend in publications from groups headed by younger principal investigators. The survey also showed that most groups established in the 1980s are still regularly active and have a significant impact on the scientific community.  IMBIM scientists have received several large competitive grants and are active in several Swedish and international networks. Smaller groups, however, have experienced problems in winning external grants. The recently adopted policy by the Swedish Research council to give larger grants to fewer scientists is likely to affect groups at IMBIM during the coming years. This provides a further example of the tendency to distribute research funds among fewer but increasingly successful and larger groups. Eventually, this will lead to fewer fully independent research groups in a department the size of IMBIM and demands new departmental policies. The current trend is leading to problems affecting the maintenance of the broad competence that is so important for undergraduate teaching of quality. Furthermore, departments must adopt long-term recruitment plans so that new groups fit with strong research areas already represented, but this can potentially create a static situation with little renewal of research areas. An analysis of the departments and associated scientists preceding the advent of IMBIM shows that several novel research areas developed from existing strong scientific milieus and where this type of dynamic was encouraged by the leadership of the time. The departments and individuals that adopted such a policy often turned out to meet with most success in the long run. The situation is different today due to the relative lack of risk funds and the large number of fully independent groups. Presently, even some larger groups are dependent fully on external grants and contracted, time-restricted research, leaving little room for risk-taking and renewal. Faculty funds stand for an increasingly smaller proportion of the total and by themselves are not realistic sources of continued renewal. The consolidation of the various research constellations at IMBIM, together with initiatives such as SciLifeLab-U, may allow IMBIM to adopt a policy for renewal before the anticipated, significant changes in the coming decade due to several retirements.  Several scientists at IMBIM have contacts with local industry and patents have been filed. In addition to networking with industrial partners, researchers at IMBIM have ongoing programs with clinical scientists on translational approaches, aimed at applying the results of basic research to healthcare.  Several scientists have received prestigious awards during 2010. ProfessorKerstin Lindblad-Tohwas awarded The Thuréus prize andDr. Carl-Johan Rubinreceived The Benzelius award from The Royal Society of Sciences in Uppsala; Associate ProfessorPer Jemthreceived The Swedberg Award from The Swedish Society for Biochemistry and Molecular Biology; Associate ProfessorAnna-Karin Olssonreceived The Oscars’ Prize
from Uppsala University; Associate ProfessorClaës Linderreceived The Gender Equality Award 2010 from Uppsala University; and, finally Dr.Sara Thorslundand Associate ProfessorJohan Kreugerby ALMI.were named Innovators of the Year 2010 in Uppland The department congratulates these individuals on these prestigious and well-deserved marks of distinction.  Details of the research activities at IMBIM are summarized later in this annual report. Here are just a few of the highlights: A central question in evolutionary biology and other areas of biology is how and why mutations affect an organism's capacity to reproduce. In this work, Peter Lindet al. (Science. 330(6005):825-7) examined the impact of random mutations in two ribosomal genes on the growth rate of the bacterium,Salmonella enterica. Surprisingly, most mutations had very small effects on growth rates (0.5%), regardless of whether they changed protein sequence or not. On average, therefore, synonymous mutations that did not change the protein sequence actually had negative effects similar to those of non-synonymous mutations that resulted in amino acid substitutions. A possible explanation is that random mutations generally confer their negative effect by altering mRNA (structure/level), and not proteins, as is commonly assumed. Anna-Karin Olsson and co-workers have developed a new principle for tumor vaccination based on transiently overcoming self-tolerance and targeting vascular proteins selectively expressed in the tumor vasculature. Huijbers, al.(FASEB J. 24:4535-44) published a proof of principle study on animals, demonstrating the feasibility of this novel approach. In eukaryotic cells most of the DNA is in a tight complex with histone proteins, forming nucleosomes. How the transcription machinery gets access to the nucleosomal DNA in order to make RNA copies is poorly understood. To better understand changes in the chromatin during transcription, the research group lead by Pernilla Bjerling monitored nucleosome occupancy genome-wide in the yeast,Schizosaccharomyces pombe,before and after a transcriptional induction. They found that nucleosomes are lost over the entire gene body during gene activation. This is an important observation, leading to a deeper understanding of the complex process of gene regulation. (Kristell, al. Genome Research 20:361-71) In a report published in Nature, Leif Andersson and his colleagues pioneered the use of next generation sequencing for population-based whole genome sequencing. In this study, they screened eight different populations of domestic chicken as well as their wild ancestor, the red junglefowl. The study constitutes a great advance in chicken genomics as almost 7.5 million SNPs were found, a number of convincing selective sweeps were documented and almost 1300 deletions were listed. One of the most striking observations was that all tested domestic chickens representing more than 30 breeds from different parts of the world carried the same missense mutation at theTSHRgene encoding the thyroid stimulating hormone receptor. This is one of the many interesting findings that must be pursued in the coming years. (Rubin, al.Nature 464:587-91) Infection by human papillomavirus may lead to cancer. The virus produces a number of proteins to achieve a hostile takeover of the cell. One of those proteins is the E6 protein,
which targets several human proteins important for cell regulation, including SAP97. The group of Per Jemth studied how fast the E6 protein binds to and dissociates from SAP97, how strongly it binds, and how it effects the shape of SAP97. It has proved difficult to stop the proliferation of viruses using conventional drug discovery and the hope is that fundamental biophysical studies will open up new routes for drug design. The paper was published in J. Biol. Chem. by Chi, al.(286:3597-606:Epub 2010 Nov 27.) and was named paper of the week by the journal.  IMBIM scientists participate substantially in undergraduate and graduate teaching at the Faculties of Medicine and Pharmacy. Under the auspices of the graduate program, fourteen students have received their doctoral degrees and one student has been awarded a licentiate degree. The undergraduate teaching by IMBIM scientists is substantial and generally well received. It is a departmental policy that all scientists at different levels should participate in teaching and this goal has been largely fulfilled. Students thus have access to teachers who are experts and who are actively involved in research in their chosen fields. This guarantees that teaching is up to date and helps students to see the frontline of many research areas. The Faculty has adopted pedagogic programs for all teachers and it is thus anticipated that the pedagogic competence of teachers at IMBIM will continue to increase.  Finally, although IMBIM has a strong and effective administration, the many and various new legislations and initiatives from central administrative bodies have greatly increased its workload. The Chairman of IMBIM welcomes an initiative by the central administration of the university to create a dialogue with the departments so that their needs will be better understood. This may help departments such as IMBIM in their work to fulfill the three central tasks of the university; to conduct research, to advance teaching and spread scholarship, and to help turn the results of these endeavors to the benefit of society. Uppsala, March 2011 Kristofer Rubin, Chairman
LIST OF CONTENTS ADDRESS LIST ORGANIZATION SCIENTIFIC REPORTS OF RESEARCH GROUPS Comparative Genomics  Andersson Leif:Functional genomics in domestic animals Bjerling Pernilla:Chromatin dynamics Jern Patric:Host-retrovirus evolution Lindblad-Toh Kerstin:Comparative genomics and genetics Webster Matthew:Genomic evolution Medical Biochemistry Glycobiology Annerén Cecilia:Molecular mechanisms regulating pluripotency and  self-renewal of embryonic stem cells Kjellén Lena:Cellular design of heparan sulfate Kreuger Johan:Functional studies of blood vessel guidanceLi Jin-ping:Heparan sulfate: Implications to animal development and pathophysiological processes Spillmann Dorothe:The connection between out- and inside of a cell – Can glycosaminoglycans tune cellular control?  Medical Protein Chemistry Ek Pia:Regulation by phosphorylation Engström Åke:Expression proteomics Fries Erik:Intracellular processing of secretory proteins Jemth Per:Structure-function relationships of proteins Schedin-Weiss Sophia:Serine proteases and serpins in blood coagulation, inflammation and reproduction Tomkinson Birgitta:Structure, function and physiological role of tripeptidyl-peptidase II  Tumor biology Gerwins Pär:Mechanisms of tissue vascularization Johansson Staffan:Adhesion-dependent cell signaling Moustakas Aristidis:Signal transduction and epithelial plasticity Olsson Anna-Karin:Tumor vascular biology Ringvall Maria:Regulation of tumor angiogenesis Rubin Kristofer/Rydén Cecilia:Loose connective tissues – Targets for novel therapies in cancer and infectious diseases Sundberg Christian:Mechanisms of optimal tissue regeneration versus fibrosis and the role of the microvasculature Åbrink Magnus:Mast cell proteases in chronic and pathogen induced inflammation
1415 16 23 26 28 37
41 44 47
59 60 62 64 66
74 75 78 80 85 88 90
Medical Microbiology Immunology Heyman Birgitta:Antibody feedback regulation Henningson Johnson Frida:Biological role of CD23, the low affinity  receptor for IgE Hallgren Martinsson Jenny:Mastcells and their progenitors in allergic  airway inflammation (asthma) Grönvik Kjell-Olov:Prophylactictreatment with IgY antibodies to control  infection by influenza viruses  Molecular BacteriologyAndersson Dan:Tempo and mode of bacterial evolution Hinas Andrea:Uptake and spreading of RNA interference between cells  in animals Sandegren Linus:Persistence and evolution of plasmid-borne antibiotic  resistance Swedberg Göte:Mutations and genetic transfer contribute to evolution  and stable persistence of drug resistant microorganisms  Molecular Virology/Viral Model Systems Akusjärvi Göran:Adenovirus in basic and medical research Magnusson Göran:Replication and genetic stability of polyomavirus Schwartz Stefan:Viral gene regulation Svensson Catharina:Adenovirus type 12 induced interferon response SCIENTIFIC PAPERS PUBLISHED 2010PRIZES AND AWARDS AT IMBIM DISSERTATIONS AND LICENTIATE THESIS 2010ECONOMY 2010UNDERGRADUATE TEACHING AT IMBIMTHE PhD PROGRAM AT IMBIM RESOURCE CENTRES AT IMBIM Centre for comparative disease genetics and genomics  Facility for Recombinant Adenovirus Construction  Proteomics Resource Centre  Swedish Network in Medical Glycobiology – MEDIGLY  Uppsala Graduate School in Biomedical Research – UGSBR  Uppsala University Transgenic Facility – UUTF Science for Life Laboratory in Uppsala LIST OF AUTHORS
101 102
112 113
135 136 142 144 149
164 164 165 166 167 168 169
ADDRESS LIST Department of Medical Biochemistry and Microbiology, IMBIM Address: Uppsala University, IMBIM, Box 582, 751 23 Uppsala, Sweden Office: Fax +46 18 471 4673, Phone +46 18 471 4444, +46 18 471 4561 Adler Marlen Akusjärvi Göran Amin Amira Andersson Dan Andersson Eva Andersson Leif Annerén Cecilia Arendt Maja Louise Axelsson Erik Azarbayjani Faranak Backström Ellenor Barkefors Irmeli Beckman Sundh Ulla Berglund Jonas Bergman Anna Rolfsdotter Bjerling Pernilla Björnerfeldt Susanne Busch Per Cardoso Carlos Carlsson Anette Cedervall Jessica Chi Celestine Dagälv Anders Dahlin Joakim Deligny Audrey Ding Zhoujie Do Anh-Tri Dogan Jakob Dorshorst Ben Ek Pia Eklund Anders Eklund Sandra Engström Eva Engström Åke Enström Erika Enweji Nizar Eriksson Anna Eriksson Inger
Eriksson Jonas Femel Julia Forsberg Maud Fries Erik Friman Tomas Fredlund Fuchs Peder Fuentes Alexis Garpenstrand Katarina Holmborn Gerwins Pär Gilbert Elizabeth Golovko Anna Gorniók Beata Filipek Gottfridsson Eva Grönvik Kjell-Olov Gullberg Erik Gupta Rajesh Gustafsson Renata Hallgren Martinsson Jenny Haq Syed Raza Heldin Johan Hellström Anders Henningson Johnson Frida Heyman Birgitta Hinas Andrea Hjertström Elina Hjälm Göran Huijbers Else Hultqvist Greta Imsland Freyja Ingvarsson Henrik Jemth Per Jern Patric Jiang Lin Johansson Cecilia Johansson Cecilia Johansson Staffan Karén Jakob Karlsson Andreas Kasza Zsolt Kerje Susanne Kheir Amany Kjellén Lena Koskiniemi Sanna Kreuger Johan Kristell Carolina Lan Xin Li Jin-ping Anders.Hellströ Jakob.Karé
Li Xiaoze Lidholt Kerstin Lind Peter Lindahl Ulf Lindberg Catharina Lindblad-Toh Kerstin Linkevičius Marius Lofton Hava Lowisin Barbro Lundgren Susanne Lundin Lars Lustig Ulrika Magnusson Göran Martinez Barrio Alvaro Meadows Jennifer Moustakas Aristidis Murén Eva Nicoloff Hervé Noborn Fredrik Nordli Olav Näsvall Joakim Olsson Anna-Karin Olsson Maria Persson Heidi Törmänen Persson Lena Pielberg Gerli Rosengren Pijuan Galitó Sara Pränting Maria Punga Tanel Ramachandra Rashmi Rask Lars Ratnakumar Abhirami Reyhani Vahid Riaz Anjum Ringvall Maria Riviera Patricio Rodriguez Alejandro Roy Ananya Rubin Carl-Johan Rubin Kristofer Rutemark Christian Rydén Cecilia Sandegren Linus Schwartz Stefan Sköld Ola Sollander Karin Somberg Monika
Spillmann Dorothe Strandberg Johanna Strömbom Malin Sun Song Sun Wei Sundberg Christian Swedberg Göte Svensson Catharina Svensson Mervi Söderhäll Carin Sörby Maria Tamm Christoffer Tengvall Katarina Thorslund Sara Thulin Elisabeth Tingsborg Susanne Tobin Christina Tomkinson Birgitta Wang Bo Wang Chao Wang Jian Webster Matthew Schedin Weiss Sophia Wigenius Marianne Wu Cheng Jun Wärmegård Birgitta Zeller Kathrin Zetterqvist Örjan Zhang Xiao-Qun Zhao Yani Zorzet Anna Åbrink Magnus Åkerblom Rehné Östberg Sara