University of Manchester (UNIMAN), Manchester, United Kingdom
The Manchester Centre for Integrative Systems Biology (MCISB) is one of the six BBSRC/EPSRC funded Centres for Systems Biology in the United Kingdom, with Oxford the only one that combines this with being one of three EPSRC/BBSRC funded Doctoral Training Centres for Systems Biology (DTC-ISBML; 50 PhD students). It is established across the faculties of the university, and thereby completely interdisciplinary between physics, chemistry, engineering, biology, medicine and pharmacy. The MCISB has developed a complete set of methodologies for systems biology, ranging from well-defined steady-state experimentation and quantitative functional genomics to intensive mathematical modelling, bioinformatics and text mining. The MCISB has led the generation of the consensus genome-wide metabolic map for yeast, integrating a number of diverse such metabolic maps, and has now almost finished doing the same for the human genome- wide metabolic map. In this process MCISB has amply exercised the many organizational (and psycho- sociological) procedures it will put in place in this project, e.g. Jamborees, wiki-nets, modularization, workflows, and quality control. The MCISB has also produced one of the first complete (TAVERNA) workflows ever that integrates experimentation, literature information and modelling. After proofing the methodologies in yeast, the MCISB is now involved in more than 30 applied research projects across the University and with industries and clinics. These include projects on anti-cancer drug design, drug toxicity management, biomarker discovery for prenatal diseases, functional genomics analyses of diseases, well engineered-biopharmaceutical production, and multiple network-based drug targeting.
Hans Westerhoff has been a Systems Biologist avant la lettre. He is AstraZeneca Professor for Systems Biology at the University of Manchester and director of both the MCISB and the DTC-ISBML. He is also effective co-leader of the Systems Biology ESFRI, which is now in its first phase. Westerhoff is coordinating a Systems Biology project that includes five European nations (MOSES) and involved in 6 other such transnational research projects. He holds a research-funding portfolio in systems biology of well over €10M. Westerhoff has been chair of the Advisory Board of the multimillion German (BMBF) Hepatosys research program, as well as of the committee advising on the formatting of its successor 'The virtual Liver'. He is also in the four-membered scientific advisory board of the €100M Luxemburg systems biomedicine program, as well as director of the biennial FEBS Advanced Lecture Course on Systems Biology. Through Hans Westerhoff and Jacky Snoep there is a personal union with the VU University of Amsterdam (VUA, participant 4) where they both hold part-time professorial appointments. Professors Carole Goble (involved in multiple data management projects) and Jacky Snoep co-coordinate the SysMO-db, the largest systems biology driven data and model management system of Europe. Snoep drives the live model repository JWS- Online. The MCISB with its scientific board of 7 additional Systems Biology related Professors and 10 dedicated research officers, including a manager, will support the proposed research programme.
Profile of staff members
Hans Westerhoff is AstraZeneca Professor of Systems Biology at the University of Manchester, and Professor of Microbial Physiology at VUA and directs both the MCISB and the DTC-ISBML. Jacky Snoep is Professor of Systems Biochemistry at UNIMAN and VUA. Dr Daniel Jameson is IT scientist and research manager at the MCISB.
Recent publications relevant to the project
1. Kolodkin A.N., Bruggeman FJ, Plant N, Moné MJ, Bakker BM, Campbell MJ, Van Leeuwen JPTM, Carlberg C, Snoep JL and Westerhoff HV (2010) Design principles of nuclear receptor signaling: how complex networking improves signal transduction. Mol. Systems Biology 6; doi 0.1038/msb.2010.102
2. Li P, et al. (2010) Systematic integration of experimental data and models in systems biology. BMC Bioinformatics 11:582.
3. Westerhoff HV, et al. (2009) Systems biology towards life in silico: mathematics of the control of living cells. Journal of Mathematical Biology 58, 7-34.
4. Monkhorst K, et al. (2009) The Probability to Initiate X Chromosome Inactivation Is Determined by the X to Autosomal Ratio and X Chromosome Specific Allelic Properties. Plos One 4.
5. Herrgard MJ, et al. (2008) A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nature Biotechnology 26, 1155-1160.