The University of Southampton
Biological Sciences
Phone:
(023) 8059 4222
Email:
J.M.East@soton.ac.uk

Professor Malcolm East BSc, PhD

Professor of Biochemistry, Principal Investigator (Membrane proteins)

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Professor Malcolm East is Professor of Biochemistry within Biological Sciences at the University of Southampton.

Career History

2014-present: Professor of Biochemistry. University of Southampton, UK.
2005-2014: Reader in Biochemistry. University of Southampton, UK.
1993-2005: Senior Lecturer. University of Southampton, UK.
1987-1993: Lecturer, University of Southampton, UK.
1984-1987: Wellcome Lecturer. University of Southampton, UK.
1980-1984: Post-doctural Research Fellow. University of Southampton, UK.

Academic Qualifications

1981: PhD Open University, UK.
1975: BSc Applied Biology. Hatfield Polytechnic, UK.

Research

Publications

Contact

Research interests

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.

Research group

Molecular and Cellular Biosciences

Research project(s)

Anionic lipids in cell signalling: a mechanism for the modulation of ABC multidrug transporters

It is becoming apparent that lipids in biological membrane do more than simply provide a permeability barrier in which the membrane proteins are embedded. Here we investigate their role in binding to and modulating the activity of a model membrane protein.

Calcium Pumps and Thermogenesis

We are investigating the mechanism by which uncoupling of calcium transport is achieved. In addition, we are examining sarcolipin levels in muscle tissue.

Calcium Pump Targeting

We are currently investigating the way in which calcium pumps and their modulators, phospholamban and sarcolipin, are targeted to the relevant organelles in cells.

Structure and Function of Membrane Proteins

Although significant advances have been made in obtaining crystal structures of membrane proteins, very few membrane proteins have been crystallised. Certain parts of the structure still remain elusive.

Articles

Professor Malcolm East
Biological Sciences
Faculty of Natural & Environmental Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

Room Number:85/3041

Telephone:(023) 8059 4222
Email:J.M.East@soton.ac.uk

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