Tom Duke
Teaching
Miscellaneous
Signalling networks: Signal transduction is one of the fundamental functions of the cell. Information gathered by membrane receptors is processed within the cell by a complex network of interacting signalling proteins, which then elicits an appropriate response. We are investigating the physical mechanisms and network architectures that underpin key properties of signal transduction systems, such as sensitivity to weak signals, adaptation to unchanging signal levels and resilience to fluctuations in protein number.
Collaborative receptors: Receptor proteins in both eucaryotic and prokaryotic cells have been found to form two-dimensional clusters in the plasma membrane. We have proposed that such clusters might show coordinated responses due to the spread of conformational states from one receptor to its neighbours. When cooperative interactions between adjacent receptors are close to a critical level, a cluster displays a greatly enhanced sensitivity to external signals, and is operational over a much wider range of ambient concentrations. These and other properties should make a lattice of conformationally coupled receptors ideally suited to act as a 'nose' by which a cell can detect and respond to extracellular stimuli.
Protein switches: Logical operations in the cell require molecular switches that can be sensitively controlled by the concentration an effector molecule. We have shown that, given suitable values of conformational free energies, a ring of allosteric proteins can exhibit a switch-like response to changes in ligand concentration with maximum sensitivity proportional to the number of proteins in the ring. A ring of this kind can reproduce the performance of the switch complex of a bacterial flagellar motor, for example, which is based on a ring of 34 FliM proteins.
