Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Postgraduate Research Studentships

Department of Biochemistry Studentships

In collaboration with the Medical Sciences Division and Colleges, the Department awards a number of Postgraduate Research Studentships each year. These are full awards that will cover University and College Fees and funding for living expenses. All applicants that apply by the early January deadline will automatically be considered for one of these awards.

 


Group Leader and Project-specific Studentships

In addition to Department of Biochemistry Studentships, we occassionally advertise studentships that are associated with a specific Group Leader or Project. Details about these studentships are given below.

There is one Group Leader/Project-specific Studentship currently being advertised

3-YEAR PhD Studentship on target-based antimalarial drug discovery

Department of Biochemistry, University of Oxford

Main academic supervisor: Associate Prof John Vakonakis

Please quote Studentship Source Code: STU1

PROJECT DESCRIPTION

Background

Malaria is one of the most lethal infectious disease, killing an estimated 450,000 people each year and infecting millions more in developing countries. Tha majority of victims are children under the age of five who develop severe disease forms. However, no new antimalarial drugs have been licensed for frontline use since the introduction of artemisinin in 2000. Artemisinin combination therapies are now the standard worldwide treatment for malaria. Since 2008, and increasingly in recent years, malaria parasites have developed resistance to artemisinin. The spread of these artemisinin resistant parasite strains in now having a very significant negative impact in our ability to cure malaria; as a result, new treatments of malaria are urgently needed.

In my group we seek to understand at the molecular level the processes that enable malaria parasites to survive and grow inside the human red blood cells they invade, so that we may target these processes with novel antimalarials. We are particularly interested in parasite processes that have no counterpart in normal human cells, as drugs targeting these processes may cause fewer side-effects.

Project

One of the most promising parasite-specific processes for antimalarial drug development is the digestion of human haemoglobin. Parasites derive essential nutrients from haemoglobin digestion; however, they also face the problem of what to do with the large amounts of heme released by this digestive processes. Soluble heme is toxic as it drives the formation of free radicals that can damage proteins, nucleic acids and lipids. Malaria parasites 'solve' this problem by ploymerising heme to an inert crystalline form, which can be safely stored in cells. Some of the most successful antimalarial drugs, such as chloroquine, act by blocking heme polymerisation, thereby leading to oxidative damage and death of the parasite.

Heme polymerisation in malaria parasites is catalysed by a single enzyme, heme ligase, that has no similarity to humon proteins. Genetic data suggest this enzyme is essential for parasite survival. However, to date there is no information on the structure and catalytic mechanism of heme ligase that would enable the development of enzyme inhibitors. Thus, the main aims of this PhD studentship will be (1) to understand heme ligase at the atomic level, and (2) to identify promising lead molecules for heme ligase inhibition.

Outcome

My group has extensive experience in the structual analysis of proteins by both X-ray crystallography and NMR spectroscopy. The incoming PhD student will be trained in these methods as she/he works towards the structual characterisation of heme ligase. We have establisged a collaboration with Cloudpharm (http://cloudpharm.eu) for the identification of putative heme ligase inhibitors using computational approaches once the enzyme structure is resolved, and with OxXChem (http://xchem.github.io/oxxchem/) to identify putative inhibitors using an experiment-based high-throughput approach. Finally, we have an established collaboration with the Parasite Chemotherapy Unit of Swiss Tropical and Public Health Institute (SwissTPH, Basel) (https://www.swissthp.ch/fr/about/mpi/parasite-chemotherapy/) to test the effectiveness of inhibitors against malaria parasites in cultues. We envision that the PhD student spend part (~6 months) of his/her studies at the SwissTPH to conduct parasite assays, thereby gaining valuable interdisciplinary experience beyond structual biology and biophysics.

 

Further information and background reading:

http://www.bioch.ox.ac.uk/aspite/index.asp?sectionid=vakonakislab

Students with a molecular biology, biochemistry or biophysics background, ideally with some relevant practical undergraduate experience, would be preferred.

Informal enquiries are welcome; please email Prof. Vakonakis (ioannis.vakonakis@bioch.ox.ac.uk)

The project is supported by a 3-year PhD studentship covering fees (at the Home/EU rate) plus a living cost allowance of not less than £14,777 per annum.

To apply for this funded studentship, please submit an online application to the University of Oxford for admission to the D.Phil. in Biochemistry (course code: RD_BC1) by the deadline 12.00 (UK time) 11th January 2019. It is very important that you quote Studentship Source Code STU1. No research proposal is required as part of the application. Instead you are required to upload a personal statement of no more than 100 words, describing your motivation and aptitude for this position, and your CV, plus including official transcripts of your undergraduate marks and degrees. Please arrange that three referees directly submit references for you.
 


 

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