PhD Studentships

Division of Cellular & Molecular Medicine
St. George’s University of London

Applications are invited for 3 full-time 4-year research PhD Studentships supported by the Pathology Research Fund at St. George’s University of London. The studentships cover fees (at ‘home’ student rates) and provide a stipend at UK Research Council rates (starting stipend of £15,598).

Applicant should have a first or upper second class honours degree or MSc/MRes in an appropriate discipline.

Informal enquiries should be made to the lead supervisor of the relevant project. Applications containing a covering letter, CV and details of two academic referees should be sent to R. Halms (rhalms@sgul.ac.uk) with the subject line containing ‘Path Research PhD Studentships’, by 12th January 2010. Interviews will be held at SGUL on 11th February 2010

Project Supervisor: Dr Yanmin Hu
Second Supervisor: Professor Anthony Coates

Title of project: A study of the mechanism of action of a novel anti-MRSA antibiotic

The supervisors have invented a new route for antibiotic discovery. This has led to a new anti-MRSA topical antibiotic which is in Phase II/III clinical development.
The project aims to study the mechanism of action of this new antibiotic, which acts faster, induces less resistance and is more bactericidal than most current antibiotics. The antibiotic kills bacteria in several different ways, including depolarisation of the membrane and destruction of the cell wall. The student will develop assays which measure depolarisation of the membrane, and will use electron microscopy to study different conditions which lead to cell wall degeneration. Attempts will be made to generate a mutant S. aureus which is resistant to it. The molecular basis of HT61 action will also be investigated using transposon mutagenesis. Any resistant mutant which is found will have its genome completely sequenced in order to find the gene which has mutated. HT61 will be radiolabelled, and the student will study to which molecules it binds. Any gene which is thought to be involved will be genetically deleted, and subsequently complemented. This will provide further information about the mechanism of action of the new antibiotic.

Project Supervisor: Professor T J Chambers
Second Supervisor: Dr Jade Chow
Title of project: Why does oestrogen treatment fail to reverse the bone loss caused by ovariectomy.

Throughout life, bone maintains its structural integrity by continuous resorption by osteoclasts and replacement by osteoblasts. These processes are closely coupled, such that, at any given site, bone resorption is normally followed by bone formation. After the menopause, the fall in oestrogen levels causes an increase in bone resorption. However, the consequent increase in formation is inadequate, and bone is lost. A major problem in the treatment of osteoporosis is that, while the excessive bone resorption can be inhibited by a variety of therapies, including oestrogen replacement, bone formation is also suppressed, so that the patient remains osteoporotic.
It would be of obvious interest to find the explanation for this. The explanation might be simply that oestrogen and other anti-resorptives suppress bone formation. Alternatively, there may be other hormones produced by the ovary that are not replaced in traditional oestrogen replacement therapy. The aim of this project is to distinguish between these possibilities.


Project Supervisor: Dr Frances Gibson
Second Supervisor: Dr Tim Rutherford
Third Supervisor: Dr Yaw Ohene-Abuakwa
Title of project: Delineation of the sequence of apoptosis: Which stage of apoptosis defines commitment to cell death?

The term apoptosis or programmed cell death defines a genetically determined form of cell death, which is morphologically and biochemically distinct from necrosis. For apoptosis to occur, a selection of molecular pathways must be activated, which involves pro-enzyme cleavage and mitochondrial disruptions. Apoptosis is tightly regulated by various components throughout the cascade of apoptosis.

Our aim is to investigate the sequence of apoptosis using a variety of techniques and to more clearly assign apoptosis detection methods to specific stages of the pathways. The formation of an accurate map of apoptosis stage/sequence versus detection technique/s will allow researchers to more accurately quantitate cells at different stages of apoptosis.

At a certain point in the cascade to apoptosis, does a cell become committed to apoptosis, and apoptosis becomes irreversible (the point-of-no-return)? When does this occur in the pathway of apoptosis? Our further aim is therefore to determine the stage of apoptosis that corresponds to this commitment to cell death.