The main goal of the Manchester Centre for Integrative Systems Biology (MCISB) is to bring together the technologies and skills necessary for the development of quantitative Systems Biology. These technologies and skills encompass a wide range of experimental (Molecular Biology / Biochemistry / Biophysics), mathematical and computational (Modelling / Data Integration / Text Mining etc.) activities. While the methods developed are intended to be generic, we seek to demonstrate their utility with a real system. To this end, the initial focus of research is on the baker's yeast (Saccharomyces cerevisiae), which is an ideal organism in which to explore techniques for the development of integrated models of important cellular systems, because the organism is highly amenable to genetic manipulations and to high-throughput technologies.
Specific aims and objectives
Four major research foci constitute the core of MCISB activities. The first focus is on the development and exploitation of methods for the quantitative measurement of kinetic and binding constants on a genome-wide scale. The second focus is to develop and implement quantitative omics technologies (metabolomics and proteomics) which can be used in any organism for which the genome has been fully sequenced. The third focus is on the iterative forward and inverse predictive modeling of the yeast metabolic system, fortified with high-quality experimental data representing the concentrations of transcripts, proteins and metabolites. The fourth focus is to mine existing sources of information (both text and data resources), and to integrate these sources with the data generated in the MCISB project. The combination of these approaches will lead to computer models of parts of living cells. Some of these 'silicon cells' are already available for in silico experimentation, through the Biomodels and JWS databases.
The following technologies are the focus of ongoing research: medium-to-high-throughput production and purification of biomolecules (predominantly of tagged proteins), qualitative genome-wide binding assays (protein-ligand and protein-macromolecule) to establish the structural interaction network, quantitative genome-wide ligand and inhibitor binding and enzyme kinetic assays, quantitative metabolomics (chiefly GCxGC-MS and LC-MS), quantitative proteomics (LC-MS and MALDI of crude extracts, employing sets of engineered, unique peptides that are protein-specific), integrated bioinformatics strategies (focusing on service-based infrastructures), and quantitative mathematical modeling (forward and inverse modeling). A specific development is that we consider that Integrative Systems Biology is best effected via loosely coupled bioinformatics workflows, and we are concentrating significant effort into developing workflows using Taverna for these purposes.
Research staff and scope for collaborations
The MCISB employs staff who are experts in a variety of fields including microbiology, molecular biology, protein purification, bio-molecular interaction, metabolomics, proteomics, mathematical modeling of biological processes, data analysis, data standards and databases. The MCISB is open to suggestions for new, collaborative projects in systems biology. All suggested projects will be discussed in the MCISB Management Board. Interested colleagues should initially contact the project manager Dr Dieter Weichart. More details on specific areas of collaboration are listed below:
Protein production. We produce S. cerevisiae proteins. Protein expression is performed using controlled yeast expression system. The affinity tag based protein purification method allows purifying up to 1mg of protein per 5g of yeast. We can produce proteins on the small scale for biochemical or biophysical studies. Available strain collection provides good opportunity to produce almost every yeast protein. Protein complex purification is also feasible. Contact: Dr Naglis Malys