Funding boosts membrane protein studies in department

Two recent successes in the Biochemistry department to secure grant funding will help researchers there pursue their studies on exploring how membrane proteins carry out their pivotal roles in the cell.

Molecular simulation showing recognition of the phospholipid PIP3 by a PH domain of a protein

Molecular simulation showing recognition of the phospholipid PIP3 by a PH domain of a protein

Professor Mark Sansom, who heads the Structural Bioinformatics and Computational Biochemistry Unit within the department, and Dr Phil Biggin, a group leader in the unit, have been awarded grants from the Wellcome Trust and the Leverhulme Trust respectively.

Membrane proteins play crucial roles in the cell. They often act as intermediaries, transmitting a signal from the outside of the cell to the inside. The signalling systems which they are part of control many processes ranging from the development of tissues to immune responses. Errors in membrane signalling are associated with many diseases including cancer and diabetes, so the proteins are an intense area of focus.

The Structural Bioinformatics and Computational Biochemistry Unit explores how the structure of membrane proteins is related to their function. These proteins undergo structural changes as they propagate a signal across the membrane, and the group uses computational methods to simulate these changes and relate them to how the cell responds. A more detailed understanding of this aspect of membrane protein biochemistry is important for developing new therapies against disease.

Cartoon of the glutamate receptor embedded in a lipid bilayer.  The structure is that of the 'closed' state

Cartoon of the glutamate receptor embedded in a lipid bilayer. The structure is that of the 'closed' state

The grant to Professor Sansom represents a new direction for his research group. It builds on the group's expertise in molecular simulations, but the aim will be to shift the focus of work from the membrane signalling systems currently studied to a broader range of systems - including more complex ones that are biomedically relevant.

Professor Sansom plans to do this by developing computational models using signalling systems for which there are already some good experimental data. The group will then be in a strong position to exploit the predictive capability of the models to study those biomedically relevant systems which are not so tractable experimentally.

Dr Phil Biggin's grant focuses on glutamate receptors, a group of membrane proteins found in neurons in the brain which are central to neurotransmission. The receptors are fundamental to memory and learning and are implicated in many neurological disease states.

Glutamate receptors bind the neurotransmitter glutamate once it has diffused across the synapse following activation of a neuron. Binding causes the receptor to undergo a conformational change which allows positive ions to flow into the cell membrane, leading to propagation of the nerve signal.

The recently-solved crystal structure of the receptor shows that the receptor exists in a 'closed' state, where no ions can pass through into or out of the membrane. Dr Biggin hopes to use the new grant to understand how the receptor switches to an 'open' state and what controls this. He will be using state-of-the-art molecular simulation methods to gain a picture of the dynamics of these receptors at atomic resolution.





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