SyBoSS - Systems Biology of Stem Cells and Reprogramming

Supported by the EU Seventh Research Framework Programme (FP7).

Our Partners

Prof Francis Stewart

BIOTEC TU Dresden.

Francis Stewart is the Professor of Genomics at Dresden University, Germany. After completing a PhD in molecular biology at UNSW in Sydney, he joined Prof Guenther Schuetz at the German Cancer Research Center, Heidelberg, as an Alexander von Humboldt Fellow. There, he studied how gene expression is regulated in chromatin, especially by steroid hormone receptors and other transcription factors.

In 1991, Francis Stewart became a Group Leader in the Gene Expression Program at EMBL, Heidelberg. He developed several new genetic engineering technologies including ligand-regulated site specific recombination mediated by fusion proteins combining a site-specific recombinase with a steroid-hormone binding domain. This method has since been applied in many eukaryotic model organisms, in particular tamoxifen-induced Cre-ERT2 in mice for ligand-regulated conditional mutagenesis.

Recombineering is DNA engineering based on the use of homologous recombination in E. coli. The Stewart lab first showed that the phage proteins RecE/RecT and the Red operon of lambda phage are ideally suited for many DNA engineering tasks.

In parallel to recombinative technology development, the Stewart lab also continued research on chromatin. Several protein domains that regulate chromatin structure were described, including the PhD finger. The discovery of the first histone 3 lysine 4 methyltransferase complex, yeast Set1C, led to the first linkage between trithorax-Group action and histone methylation. Subsequently it was realized that Polycomb-Group action includes histone 3 lysine 27 methylation and the opposition between trithorax- and Polycomb-Group action is mediated by the methylation status of the histone 3 tail. This opposition is central to epigenetic regulation, which now forms the central research theme.

In 2001 the Stewart lab moved to the new BioInnovations Center in Dresden. Current work is focused on understanding epigenetics in mammalian development and homeostasis by focus on the six Mll/Set1 histone 3 lysine 4 methyltransferases. The studies encompass issues involving embryonic stem cell differentiation and somatic reprogramming and benefit from recombineering and conditional mutagenesis methodologies. In particular, methods have been developed for protein tagging by BAC transgenesis and targeting to complement conditional mutagenesis and multipurpose alleles using site-specific recombination

Prof. Andreas Beyer

University of Cologne

to be updated soon

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Prof Tony Hyman

MPI-CBG Dresden

Prof Tony Hyman came to Dresden from the European Molecular Biology Laboratory in Heidelberg. Since 2000  he has been a  group leader and director at the  MPI-CBG Dresden. His laboratory concentrates on understanding spindle assembly during cell division and mitosis. He has obtained numerous awards including the EMBO Gold Medal and is a fellow of the Royal Society. Tony’s scientific work specifically focuses on the relationship between microtubule polymers and the formation of mitotic spindles . He has extensive experience in systems biology and performed the first genome-scaled screens using video microscopy and RNAi. He has also applied large-scale tagging approaches, RNAi screens and proteomics (protein-protein-interactions). Another core expertise of his group is imaging in cell polarity and mitosis using several model organism e.g. C. elegans, and eukaryotic cells (8). The laboratory is a partner of the Center for Regenerative Therapies Dresden (CRTD), the FP6 project “MitoCheck” and the BMBF NGFN-plus program “Disease Genes to Protein Pathways” (Digtop).

 

Prof Chuna Ram Choudhary

CPR University of Copenhagen

Dr. Chunaram Choudhary completed his PhD in Hematology/Oncology at the University of Muenster, Germany. He worked as a postdoctoral fellow at the Department of Proteomics and Signal Transduction at the Max Planck Institute for Biochemistry (in the group of Prof. Matthias Mann). Since 2009 he has been a group leader at the NNF Center for Protein Research, University of Copenhagen, Denmark. Chuna´s group is interested in systems-wide understanding of cell signaling networks in response to specific cellular perturbations.  For this, his group uses high resolution mass spectrometry combined with the SILAC approach to quantify protein phosphorylation and acetylation on a proteome-wide scale. During his postdoctoral studies he identified 3,600 unique lysine acetylation sites in human cells, and quantified acetylation changes in response to lysine deacetylase inhibitors. He received the Artur Pappenheim Prize from the German society of Hematology/Oncology. Chuna is also a participant in the EC project PRIME-XS. 

 

Prof Christopher Workman

CBS

Christopher Thomas Workman, PhD, Associate professor at the CBS, and leader of the Regulatory Genomics group. Chris Workman has nine years of combined biotech industry and post-graduate experience. This includes three years of postdoctoral training in a leading Systems Biology lab at the University of California, San Diego headed by Dr. Trey Ideker. He has developed a number of bioinformatic tools and analysis methods that support research in transcriptional regulation and has extensive experience analyzing gene expression microarray data from almost all technology platforms. He has recently built-up and served as the scientific coordinator of the department’s new transcriptomics core facility (opened September 2008) that specializes in custom microarrays. He has also contributed as a developer for the Cytoscape open source project and is currently a partner on number of on-going EU projects.

Prof Bill Skarnes

Sanger Institute, Cambridge University

Bill Skarnes, Wellcome Trust Senior Investigator is a developmental biologist who pioneered gene trap technology in mouse embryonic stem cells and its use in mutant screens for developmental phenotypes. He is head of the ES Mutagenesis team (Team 87) at the Sanger Institute. His team developed the high throughput targeting pipelines for the EUCOMM and KOMP knock-out programs.  Previous to this project, he established the Sanger Institute Gene Trap Resource (SIGTR;www.sanger.ac.uk/genetrap ), an extension of the BayGenomics gene trapping program he initiated in 2000 while an assistant professor at UC Berkeley. Dr Skarnes is a founding member of the International Gene Trap Consortium (www.genetrap.org/) and a member of the International Mouse Knockout Consortium (IKMC) Steering Committee.  In collaboration with the Sanger Bioinformatics Team (Team 71), Bill has taken the lead in developing tools for the IGTC to automate the annotation of gene trap sequence tags (MAPTAG;www.sanger.ac.uk/PostGenomics/genetrap/maptag.shtml) and their display position in the mouse genome browser (Ensembl DAS source 'Gene Trap'). More recently, his team has developed automated vector design software and sequence analysis programs to support high-throughput targeting vector construction and ES cell

genotyping for the EUCOMM and KOMP projects.

 

Prof Austin Smith

Cambridge University

Austin Smith PhD FRS, formerly director of the Centre for Genome Research in Edinburgh, is now Medical Research Council Professor at the Centre for Stem Cell Research (www.cscr.cam.ac.uk ) within the School of the Biological Sciences of the University of Cambridge.  Austin has pioneered molecular studies in ES cell biology, discovering the roles of extrinsic signals LIF and BMP and of intrinsic transcriptional organizers Oct4 and Nanog. His lab observed fluctuations in key gene expression in ES cell cultures and described the significance for self-renewal efficiency. They defined a central role for Erk signaling in exit from pluripotency, showed that small molecule inhibition of the Erk pathway combined with suppression of glycogen synthase kinase 3 enables efficient derivation and robust propagation of mouse ES cells, and broke the species barrier to establish the first germline competent rat ES cells. They also found that inhibiting these signals facilitates molecular reprogramming to naïve pluripotency from fibroblasts, neural stem cells and EpiSCs. In ES cell lineage commitment studies Austin established the adherent neural differentiation system. Together with Elena Cattaneo he described the generation of neural stem (NS) cells from ES cells and their comparison to foetal and adult CNS derived neural stem cells. Most recently he demonstrated the relatedness of NS cells to glioma stem cells. Austin coordinated the FP6 integrated project EuroStemCell and currently coordinates the FP7 large scale project EuroSyStem. He is a PI in the EC Projects ESTOOLs, NeuroScreen, StemStroke.

Prof Edith Heard

Marie Curie Institute Paris

Prof Edith Heard has headed the Mammalian Developmental Epigenetics team at the Marie Curie Institute in Paris since 2001 and is currently deputy director of the CNRS UMR 3215 department. The Heard laboratory has a long-term interest in X-chromosome inactivation and has developed molecular genetics tools as well as imaging techniques to examine this process at the single cell level in vivo and in vitro. The Heard lab’s mission is to understand the basis for the monoallelic regulation of X inactivation as well as the epigenetic changes that provide the memory of the inactive state. Findings from this lab have contributed not only to our understanding of the mechanism of X-inactivation, but more generally to the epigenetic changes involved in establishing and maintaining patterns of differential gene expression during early mammalian development. The Heard lab was one of the first to discover the reprogramming events affecting the inactive X chromosome during early mouse embryogenesis in the inner cell mass of the blastocyst (Okamoto et al, 2004). The lab has has expertise in chromatin, non-coding RNA, nuclear organization as well as molecular genetics (transgenesis and knock outs). They are long standing experts in the use of mouse ES cells and embryos. They also have ongoing work studying X inactivation and epigenetic dynamics in embryos from species other than mouse (human, rabbit, cow).

Edith has received multiple awards in the past 5 years including the CNRS Silver Medal, the Schlumberger Foundation Prize, the Jean Hamburger Grand Prix de la Ville de Paris, the Otto Mangold Prize. She became an EMBO member in 2005. Her research has received continuous funding and includes grants from the HFSPO, the EU (Epigenome NoE and HEROIC IP), the ANR, the FRM and others. She has organised several international meetings and workshops.

 

 

Prof Toby Gibson

EMBL Heidelberg


Toby Gibson has over 20 years of experience in computational biology, currently focused on the architecture and function of cell regulatory proteins. He coordinated the establishment of the Eukaryotic Linear Motif (ELM
elm.eu.org) resource, which contains entries for ~160 regulatory protein motifs. Among other resources developed are Phospho.ELM (phospho.elm.eu.org), an annotated database of >42,000 phosphorylation sites and EpiC (epic.embl.de), a tool for guiding epitope choice. The freely available ELM servers have many thousands of users worldwide, while the dataset is now being widely used in bioinformatic investigations of protein networks. Several European groups collaborate directly on methods for linear motif discovery. He is also a co-developer of ClustalW/X (www.clustal.org), the most widely used multiple sequence alignment software. In the context of SyBoSS, Toby is working to enhance bioinformatics standards for regulatory protein interactions. Currently these are not useful for capturing and/or simulating the cooperative in-complex molecular switching events that underpin much of cell regulation.

Prof Wolfgang Wurst

Helmholtz Institute Munich

Prof Wolfgang Wurst trained in Biology and Chemistry at the University of Freiburg, successfully concluding his postgraduate studies in 1988 at the Department of Immunogenetics, University of Goettingen. He then conducted postdoctoral experimental research in mouse embryology with Alex Joyner in Toronto, before returning to Germany in 1994 to found his own research group at the Department of Mammalian Genetics, GSF-National Research Centre for Environment and Health, in Munich/Neuherberg, Germany. In 1997 Wolfgang became an Associate Professor for Molecular Neurogenetics at the Max-Planck-Institute of Psychiatry, Munich, and the GSF-National Research Centre for Environment and Health, Munich/Neuherberg. Since May 2002 Wolfgang has been the Professor of Developmental Genetics, Dept. of Life Sciences, Technical University Munich, and Director of the Institute of Developmental Genetics, GSF-National Research Centre for Environment and Health (now the Helmholtz Zentrum in Munich) and heads the research group ‘Molecular Neurogenetics’ at the Max- Planck-Institute of Psychiatry, Munich, Germany

Wolfgang Wurst is presently coordinator of the:

German Gene Trap Consortium (GGTC; http://tikus.gsf.de/)

European Conditional Mouse Mutagenesis Program (EUCOMM; http://www.eucomm.org

Helmholtz Alliance for Mental Health and Ageing (HelMA; http://www.neuro-ageing.de/)

Disease Genes to Pathways Network  (DiGtoP (http://www.digtop.de/)

Virtual Institute of Neurodegeneration (http://www.neuro-ageing.de/virtual-institute.php)

He is also a member of the Editorial Board of Anatomy & Embryology and the Special Edition Drug Discovery Today

 

Prof Frank Buchholz

TU Dresden

Prof. Frank Buchholz did his PhD studies with Francis Stewart at the European Molecular Biology Laboratory in Heidelberg. His postdoctoral studies in California preceded the establishment of his research group at the Max Planck Institute for Cellular and Molecular Biology, Dresden. Since 2010 he has been a Professor at the Technical University Dresden. His laboratory is currently composed of three post-doctoral fellows, seven graduate students, and three technical assistants. The laboratory is a partner for the Center for Regenerative Therapies Dresden (CRTD), a DFG research center and cluster of excellence, and a member of the DFG collaborative research center 655, “Cells into tissues”, the DFG research priority program SPP 1356, “Pluripotency and Cellular Regrogramming”, the BMBF NGFN-plus program “Disease Genes to Protein Pathways”. Frank is the head of the BMBF GO-Bio program “Endoribonuclease prepared (e)siRNAs for efficient and specific transcript silencing in mammalian cells.” The core expertise of the group is in functional genomics, systems biology, mouse genetics, and molecular biology of cancer- and stem cell relevant processes. The laboratory has special skills in the development and execution of mammalian RNAi based screens (1 & 2), large-scale protein tagging in mammalian cells (3), and protein evolution (4). Frank has been a participant in EC projects FunGenES and MitoCheck.

 

Prof Søren Brunak

Technical University of Denmark

Søren Brunak, PhD, has since 1999 been Professor of Bioinformatics at the Technical University of Denmark. He is the founding Director of the Center for Biological Sequence Analysis started 1993. Søren has been a pioneer in relation to the invention and introduction of new computational strategies for analysis of data with relevance to molecular biology, medicine and biotechnology. He has recently been highly active within systems biology, specifically data integration focused on disease phenotypes, and is involved in numerous projects financed by the European Union and the NIH.

Prof Frank Grosveld

Erasmus University Rotterdam

Frank Grosveld is the Head of the Department of Cell Biology and Head of Clinical Genetics, at the Erasmus Medical Center, Rotterdam. His team members specialize in the use of genomics and proteomics to analyze transcription factor complexes and targets and long-range transcriptional interactions. The focus is on stem cell self renewal versus differentiation in hematopoiesis and neurogenesis. With the Gribnau lab they also study X inactivation and have proposed a stochastic process of X inactivation and counting regulated by a balance between factor(s) located close to Xist on the X chromosome and autosomal factors. One of these X-coded genes has now been identified and its role in X inactivation shown. To study such factors a pipeline was set up to tag transcription factors in ES cells (with Stewart and Skarnes, EuTRACC), followed by generation of mouse lines or differentiating ES cells in vitro. TF complexes and their interacting partners are identified by mass spectrometry and their target genes/sequences by expression analysis and ChIP/seq. Frank is a Fellow of the Royal Society, a Professor and Member of the Dutch Academy of Sciences and has received a number of awards including the Louis Jeantet Prize. Frank also participates in the EC projects EuTRACC (of which he is the coordinator), CiO, The Epigenome, and Molecular Imaging.

 

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