East, Malcolm - University of Southampton - Discipline of Biological Sciences

个人简介

Career History 2014-Present: Professor in Biochemistry. University of Southampton, UK. 2008-2014: Reader in Biochemistry. University of Southampton, UK. Wellcome Lecturer. University of Southampton, UK. Post-doctoral Research Fellow. University of Southampton, UK. Academic qualifications PhD Open University, UK. BSc Applied Biology. Hatfield Polytechnic, UK.

研究领域

The role of lipids in membrane protein function Membrane proteins play major roles as transporters, receptors and ion channels in cells and are also the targets for most of the drugs developed by pharmaceutical companies. A more detailed description of how these proteins work at the molecular would be of enormous benefit on a number of fronts; not least it would allow a more directed approach to drug design, but it would also provide a more profound understanding of the ways cells communicate with one another and are able to precisely control their internal environments. One area of membrane protein function that is still poorly understood is the role played by lipid components of the membrane in modulation of membrane proteins. It has long been known that the lipids which make up biological membrane contain a wide range of different molecules, but the reasons for this are unclear. If membrane proteins are removed from their membrane environment and then reinserted into a membrane of one type of lipid it can be demonstrated that different lipids affect the activity of the protein in different ways. Some lipids can inhibit and others activate the activity of certain membrane proteins. However, what is not clear is to what extent cells modulate the activity of their membrane proteins by altering the composition of their membranes. To investigate this novel mechanism of membrane protein modulation we are investigating the effect of specific lipids on the activity of a model membrane transport protein called SAV1866. We have identified potential binding sites on the membrane surface of the protein that may bind a class of negatively lipids. We are currently examining these sites to determine whether they provide a mechanism for directly controlling the activity of this protein. SAV1866 belongs to a family of transporters that include members responsible for antibiotic resistance and the development of resistance to cancer chemotherapy. These lipid sites could provide targets for drugs to tackle the problem of drug resistance. Membrane Proteins of the sarcoplasmic reticulum Eukaryotic cells which make up the complex multicellular organisms including humans have a number of internal membranes and it is important that the appropriate proteins are targeted to the correct membrane in order to provide that membrane with its particular properties. Muscle cells contain an extensive network of membranes called the sarcoplasmic reticulum. The sarcoplasmic reticulum stores the calcium responsible for muscle contraction. It also provides a "sink" for the removal of calcium from the cytoplasm to bring about muscle relaxation. This removal of calcium from the cytoplasm is performed by a calcium transporter and the process consumes large amounts of energy. The calcium pump is modulated by a small membrane protein called sarcolipin and we have shown that this modulator has the ability to alter the efficiency of the pumping process releasing the energy normally used to transport calcium as heat. We are investigating whether this process can be used to burn off excess calories and provide a mechanism to avoid obesity.

近期论文

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The effects of sarcolipin over-expression in mouse skeletal muscle on metabolic activity - Butler, John, Smyth, Neil, Broadbridge, Robert, Council, Claire E., Lee, Anthony G., Stocker, Claire J., Hislop, David C., Arch, Jonathan R.S., Cawthorne, Michael A. and Malcolm East, J. Published:2015Publication:Archives of Biochemistry and BiophysicsVolume:569Page Range:26-31doi:10.1016/j.abb.2015.01.027 Characterizing the fatty acid binding site in the cavity of potassium channel KcsA. - Smithers, Natalie, Bolivar, Juan H., Lee, Anthony G. and East, J. Malcolm Published:2012Publication:BiochemistryVolume:51, (40)Page Range:7996-8002doi:10.1021/bi3009196PMID:11331349 Multiple binding sites for fatty acids on the potassium channel KcsA - Bolivar, Juan H., Smithers, Natalie, East, J. Malcolm, Marsh, Derek and Lee, Anthony G. Published:2012Publication:BiochemistryVolume:51, (13)Page Range:2889-2898doi:10.1021/bi300153vPMID:22409348 Retrieval from the ER-golgi intermediate compartment is key to the targeting of c-terminally anchored ER-resident proteins - Butler, John, Watson, Helen R., Lee, Anthony G., Schuppe, Hans-Jurgen and East, J. Malcolm Published:2011Publication:Journal of Cellular BiochemistryVolume:112, (12)Page Range:3543-3548doi:10.1002/jcb.23281 A diversity of SERCA Ca2+ pump inhibitors - Michelangeli, Francesco and East, J.Malcolm Published:2011Publication:Biochemical Society TransactionsVolume:39, (3)Page Range:789-797doi:10.1042/BST0390789PMID:21599650 The localization of the ER retrieval sequence for the calcium pump SERCA1 - Watson, Helen R., Butler, John, Schuppe , Hansjurgen, Lee, Anthony G. and East, J. Malcolm Published:2011Publication:Molecular Membrane BiologyVolume:28, (4)Page Range:216-226doi:10.3109/09687688.2011.572566