Gavin Group
Biomolecular networks
The Gavin group focuses on detailed and systematic charting of cellular networks and circuitry at molecular levels in time and space.
Previous and current research
How is biological matter organised? Can the protein and chemical worlds be matched to understand the cell’s inner works? We can now access an unprecedented level of knowledge on the basic components of living systems; an ever-growing number of molecular players and functions are being characterised and localised. Despite this spectacular progress we still don’t understand how cellular components work collectively and achieve biological function. Our main areas of interest are:
The charting of biological networks: Biological function at cellular levels is achieved by groups of interacting proteins or protein complexes that represent basic functional and structural units of proteome organisation. We systematically chart their dynamics using biochemical and quantitative mass spectrometry approaches in S. cerevisiae, M. pneumoniae and, in the future, thermophiles or other extremophiles. Datasets produced allow an unbiased overview of important biological principles. Collaborations with groups at EMBL and incorporation of structural models, single-particle EM and cellular electron tomograms provides supporting details for larger assemblies of protein complexes. We are also part of a network of EMBL groups tackling a range of biological networks in M. pneumoniae, where we generated large-scale quantitative datasets on Mycoplasma transcription, metabolome and proteome organisation.
Development of new methods for charting new types of biological networks: While current protein-protein or protein-DNA (regulatory) networks give spectacular results, huge uncharted areas still need to be tackled. For example, many metabolites have signalling functions and many proteins are allosterically modulated by metabolites. These bindings are sometimes mediated by a variety of specialised domains; to date, though, large-scale, unbiased analyses are still largely missing. The group developed interests in new methods for the systematic charting of interactions between cellular proteomes, small molecules or metabolites. For example, in S. cerevisiae we developed a generic biochemical assay based on miniaturised lipid arrays for the systematic study of protein-lipid interactions. New avenues such as a affinity chromatography methods using immobilised metabolites as a affinity probes are being explored. We are also interested in multiplexing the assays through miniaturisation using integrated microuidic devices.
Bridging biological networks to phenotypes: Because biological function arises from extensively interacting biomolecules, it is in the context of biological networks that information encoded in genomes must be decrypted. We use networks as a molecular frame for the interpretation of phenotypic data recorded after systematic cell perturbations; these include small molecule inhibitors, gene knock-outs and mutations. We also use network analyses to design models, predictions and perturbations that can be challenged experimentally.
Future projects and goals
Further development of chemical biology methods based on affinity purification to monitor protein-metabolites interaction.
- Further development of chemical biology methods based on a affinity purification to monitor protein-metabolites interaction
- Global screen aiming at the systematic charting of the interactions taking place between the proteome and the metabolome in S. cerevisiae and M. pneumoniae;
- Develop new and existing collaborations to tackle the structural and functional aspects of biomolecular recognition.