Michael obtained his PhD at the University of Cambridge, working in the lab of Professor Jane Clarke (FRS). His doctoral studies, which focused on the folding and binding of intrinsically disordered proteins, were nominated for an outstanding thesis award. Now based in the lab of Dr Tim Nott (Department of Biochemistry, Oxford), Michael is applying his knowledge of intrinsically disordered proteins to the field of liquid-liquid protein phase separation.
The ability to compartmentalise reactants into a specific location and volume is crucial to life. Perhaps the best-known biological method of achieving this feat is the cell, which uses a lipid membrane to encapsulate its contents. Rather than being lipid based, the subcellular compartments I am interested in are predominantly formed from proteins. In response to a stimulus (e.g. cell cycle or viral infection), these proteins can de-mix from their surrounding solvent (e.g. the cytoplasm) and rapidly form subcellular liquid-like compartments. Like adding oil to water, this results in two distinct liquid phases that are separated by a membrane-less liquid-liquid interface. Molecules are able to diffuse across this interface and can be preferentially partitioned into or outside or the droplet: creating a new, stimulus responsive, compartment with specific chemical properties and reactant profiles. In an attempt to understand why these compartments have been maintained in evolution, my research focuses on investigating the formation, function and properties of these proteinacious droplets.
Crabtree, M. D., Mendonça, C. A. T. F., Bubb, Q. R., and Clarke, J. (2018) Folding and binding pathways of BH3-only proteins are encoded within their intrinsically disordered sequence, not templated by partner proteins. J. Biol. Chem. 293, 9718–9723.
Crabtree, M. D., Borcherds, W., Poosapati, A., Shammas, S. L., Daughdrill, G. W., and Clarke, J. (2017) Conserved helix-flanking prolines modulate intrinsically disordered protein:target affinity by altering the lifetime of the bound complex. Biochemistry. 56, 2379–2384.
Shammas, S. L., Crabtree, M. D., Dahal, L., Wicky, B. I. M., and Clarke, J. (2016) Insights into coupled folding and binding mechanisms from kinetic studies. J. Biol. Chem. 291, 6689–6695.