Research Interests

Mutex

Systematic integration of related datasets from different sources can be used to generate novel datasets or provide novel perspectives of data. We will use data integration to provide a new level of detail in protein interaction networks by describing the binding interfaces of interacting proteins at residue level, based on high resolution three dimensional structures in the MSD database.

This mapping will provide novel information to the user, including the detection of mutually exclusive interactions between molecules, identification of mutations and genetic polymorphisms that can affect protein interactions and hence signalling pathways, and recognition of post-translational modifications that govern interactions. This information will also be used in searching for drugs that inhibit protein-protein interactions. For example, mapping mutations within the RING domain of BRCA1, which predispose patients to breast and ovarian cancer, onto protein binding interfaces, allows their classification according to the effect on the underlying protein interaction networks. Mutations targeting canonical cysteine residues can result in misfolding of the RING domain, uncoupling BRCA1 signalling from a range of interactors (e.g. BARD1, UbcH5, ATF1, E2F, BAP1). In contrast, mutations within the BRCA1-BARD1 interface may only uncouple that particular protein interaction sub-network, but not signalling through other interactors.

Find out more about Dr Marketa Zvelebil's research on the Breakthrough Breast Cancer website