The computational and systems biology (CSB) group integrates complementary expertise in the fields of computational, structural and systems biology as well as bioinformatics and functional genomics. The research topics within the CSB include the modelling of protein structures as well as the analyses of large-scale molecular networks. It leads several data-driven research projects as well as assists other groups in the handling and analysis of -omics data sets.
Systems Biology and
Delivering improved structural model of drug-protein interactions
A growing need for new and effective drugs puts high demand on methods for screening and design of new compounds. A critical limitation is that response to drugs shows huge variation across populations groups, requiring the development for personalized medicine approaches. In particular, the genetic variability of Cytochrome P450 (CYP) drug-metabolizing enzymes is key in this setting. To predict the pharmacokinetics for individual patients, the CSB unit will analyse the structural impact of patients’ small nuclear polymorphisms within CYPs on the binding and metabolizing activity for known drugs and inhibitors. The molecular basis of such specificity and its pharmacogenomics relevance is being actively investigated using the tools of molecular modelling and structural bioinformatics.
Elucidating the mechanisms of cancer susceptibility
Inherited susceptibility to breast cancer is largely due to polygenic variation, with many hundreds of genetic variants involved. The CSB will continue to identify the genetic variants and the mechanisms involved, so as to build individual patient risk profiles, targeted screening and prevention as well as develop new approaches to cancer treatment. Next generation sequencing on normal breast tissue from patients and healthy controls will generate data for differential allelic expression (DAE) analysis that will allow the identification of new risk-associated cis-regulatory variants. Here, the CSB unit will integrate data on genetic variability and transcriptional regulation to devise new innovative methodologies to explore inherited susceptibility to breast cancer.
Deciphering structure and function of molecular networks
Cellular processes depend commonly on a large number of molecular components and their interactions. To capture the underlying complexity, comprehensive data sets as well as advanced computational methods for analysis of molecular networks are necessary. By exploiting available data as well as generating new data, the CSB will continue to reconstruct molecular networks in silico, and examine their function and dynamics following a systems-biology approach. In collaboration with other research groups within the CBMR, a focus will be set on networks underlying stem cell differentiation and oncogenesis. The constructed computational models seek to connect elementary molecular processes with their physiological manifestations.
Enhancing the computational resources and expertise at the CBMR
In the last decade, the generation of vast amounts of data has profoundly changed biomedical research. To harvest the available data and to utilize them for research goals within the CBMR, it is important to enhance in-house computational resources and expertise. The research group will thus establish a central state-of-the-art bioinformatic facility, which will be made available to members of the Centre. Of particular importance will be the implementation of computational pipelines for analysis of next generation sequencing data produced by the in-house Ion Torrent PGM platform. This will enable Centre member’s convenient and rapid analysis of their data and will strengthen the overall competitiveness of the CBMR across the multiple research themes. Finally, the CSB is an integral part of a proposal for a national network of next generation sequencer infrastructures, which will generate new opportunities for collaboration at the national and international levels.