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Gavin Group

Biomolecular networks

 Gavin Group

The group studies diverse organisms: the yeasts Saccharomyces cerevisiae, Chaetomium thermophilum (thermophilic eukaryote), the human pathogen Mycoplasma pneumoniae, and human somatic stem cells (MMPU group and EU-funded SyStemAge), with datasets contributing detailed cartographies of biological processes relevant to human health or disease. Another major goal is the generation of organism-wide, systematic datasets of protein-metabolite regulatory circuits, and hypotheses or models concerning the consequences of dysfunction in human diseases.

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

The rules that govern the behaviour of biological systems are the focus of intense research in the field of systems biology. The resulting models are expected to be predictive of different healthy and pathological conditions and might provide the general principles for the (re)engineering of biological systems. Our group has pioneered biochemical methods, coupled to quantitative mass-spectrometry, with the aim of systematically linking dynamic protein interaction networks to various phenotypes in model organisms, human cells and human pathogens. Long term, we aim to advance network biology and medicine through the integration of quantitative biochemistry, proteomics and structural biology, and define system-wide hypotheses explaining complex phenotypes and human diseases. We will contribute new strategies for the targeting of human pathologies and provide insight into fundamental principles and rules guiding biomolecular recognition.

Charting biological networks: The way biological systems organise themselves in dynamic, functional assemblies with varying levels of complexity remains largely elusive. One of our main focuses is on deciphering the molecular mechanisms of cell function or dysfunction, which relies to a large extent on tracing the multitude of physical interactions between the cell’s many components. We apply a range of biochemical and quantitative mass spectrometry approaches to organisms including yeast, a human pathogen and human somatic stem cells. The datasets guide the identification of drug targets and help us understand the mechanisms and side-effects of therapeutic compounds. Incorporation of structural models, single-particle electron microscopy, and cellular electron tomograms (collaboration with structural groups at EMBL) provide supporting details for the proteome organisation.

Development of new methods for charting new types of biological networks: While protein-protein and protein–DNA networks currently produce spectacular results, other critically important cellular components – metabolites – have rarely been studied in systematic interaction screens and remain best known for their housekeeping, metabolic functions. We currently focus on lipids and have developed new technologies with the capacity to produce systematic datasets measuring protein-lipid interactions. We designed miniaturised arrays of artificial membranes on a small footprint, coupled to microfluidic systems. We have also combined protein fractionation and lipidomics to characterise soluble protein-lipid complexes. We aim to extend the analyses to the entire proteome and lipidome and develop more generic approaches measuring all protein-metabolite interactions.

Future projects and goals

  • Development of chemical biology methods based on affinity purification to monitor protein-metabolite interactions.
  • Global screen aiming at the systematic charting of the interactions taking place between the proteome and the metabolome in the model organism Saccharomyces cerevisiae and in human.
  • Development of new and existing collaborations to tackle the structural and functional aspects of biomolecular recognition.

Chemistry at EMBL