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 are Group Leader/Project-specific Studentships 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.

 

3-YEAR DPhil (PhD) Studentship: Oxford Percival Stanion Studentship 2019

Department of Biochemistry, University of Oxford

Main academic supervisors: Professors Andre Furger and Jane Mellor

Please quote Studentship Source Code: Perci1

PROJECT DESCRIPTION

The main aim of our research is to understand how cells reprogram and adapt their gene expression in response to specific cues including biotic and abiotic stresses and during disease progression. The available DPhil project is focussing on the question of how cells adapt to sub-physiological temperatures which human cells can experience during a number of medical procedures such a cold cardioplegia and during transplant organ preservation. Whilst we have a good understanding of the processes and pathways that are activated when cells experience heat shock, we know very little about how cells adapt when they experience very low temperatures.

The project aims to address this issues. We want to understand how particular cellular pathways are activated by cold stress and determine the underlying molecular mechanisms. We have already identified a number of highly interesting genes that are activated human cardiomyocytes in response to cold shock and the successful candidate will continue to elucidate these exciting new leads.

Training Opportunities:

The successful candidate will be based in the department of Biochemistry where we have state of the art facilities and provide training opportunities in a wide range of techniques and instruments. These include training on the Ion Proton sequencing platform, training in bioinformatics, high-resolution cell imaging, cell culture, RNAseg, Netseg and classic moleculor biology techniques and gene editing approaches. The successful candidate will be supervised by Professor Andre Furger and Professor Jane Mellor.

The Scholarship

The scholarship covers course fees (at Home/EU rate) and a grant for £14,777. Awards are made for the full duration of your fee liability for the agreed course. The scholarship is jointly funded by the University and a generous endowment from Percival Stanion, an alumnus of Pembroke College where he was an undergraduate in the 1970s, and a member of the Pembroke Master's Circle as well as of its Investment Committee.

Further information and background reading:

Group website: http://www.bioch.ox.ac.uk/research/furger

Students with a molecular biology, cell biology or biochemistry background, ideally with some relevatn practical undergraduate experience, would be preferred. Informatal enquiries are welcome : andre.furger@bioch.ox.ac.uk

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.noon (UK time) 11th January 2019. It is important that you quote Studentship Source Code Perci1. No research proposal is required as part of the application. Instead you are requried to upload a personal statement of no more than 1000 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.
 

MRC ENTERPRISE (INDUSTRIAL ICASE) PHD STUDENTSHIP (ICASE) 2019

Using AI to Drive Drug Discovery for Membrane Protein Targets (Lead supervisor Prof Phil Biggin, commercial partner Vertex Pharmaceuticals)

Deadline:  12 noon (UK time) Friday 11 January 2019.

This iCASE studentship is fully-funded for four years with a stipend of £20,000 p.a., all tuition fees paid, plus a research training support grant.   The student will spend at least 3 months at Vertex. To be eligible for a full award, applicants must have no restrictions on how long they can stay in the UK and must have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship. Further details about residence requirements may be obtained here: https://mrc.ukri.org/skills-careers/studentships/studentship-guidance/student-eligibility-requirements

Project Details

This project aims to develop tools, which would accelerate the discovery for classically undruggable, inherently flexible membrane protein targets such as the Cystic Fibrosis Transmembrane Regulator (CFTR). The project will form the basis of a brand-new collaboration between Professor Biggin’s group and Vertex Pharmaceuticals. 

Cystic fibrosis is caused by any one of several defects in the CFTR protein and affects (or impacts) at least 70,000 people world-wide; in the UK alone, there are 10,000 people in the CF UK registry. There is currently no known cure and median life expectancy is less than 40 years (37 years).  Several mutations have been identified where the channel is correctly trafficked but remains functionally compromised and cannot transport chloride. Vertex first developed Ivacaftor, (Kalydeco™) a CFTR potentiator that increases chloride transport. However, the mechanism of action remains elusive and it does not work for all mutations associated with CFTR. The most common mutation is deltaF508, which is treated by two additional Vertex medicines, Orkambi and Symdeko.

Cryo-EM structures of first the zebrafish and now human CFTR in an apo, inactive state have been resolved to 3.9 Å resolution, providing for the first time an opportunity to not only investigate the mechanism by which these medicines work but also to put future drug design work on a more solid, structural footing, specifically for drugs that act at sites within the membrane.  Recently (Oct 2018), another cryo-EM (chicken) structure in the activated form was solved to 4.3 Å resolution providing the opportunity to use computational methods to explore the mechanistic differences between the inactive and active forms.

The project builds on the combined expertise of Vertex and Professor Biggin’s laboratory. This computational project will develop and apply advanced free energy calculations and machine learning techniques. Both aspects will be key to understanding how CFTR, and indeed other membrane proteins, can be targeted in a rational, structural fashion. In addition, the substantial experience of Vertex in terms of developing small molecules for such targets, alongside assay and synthesis expertise, will allow us to validate the computational predictions performed in this project in a prospective manner.

The overall aims of the project are:

  1. To develop and validate new methodologies for membrane protein-drug interactions, building on the previous work in the Biggin group, with particular focus on free energy calculations and rapid pose prediction using deep-learning.
  2. To assess the dynamic behaviour of target proteins, such as, but not limited to, CFTR, and their interaction with small molecules in bilayer systems that mimic the in vivo composition.

 

This project combines several related disciplines. No previous computational experience is necessary, but an up to date awareness of machine-learning and/or molecular simulation would be advantageous. A good background in chemistry would also be useful.

HOW TO APPLY

Before applying for this position, we recommend you contact Prof Biggin for informal discussions. To make a formal application, please complete the University’s online application form for the DPhil in Biochemistry (course code RD_BC1). In your application, you must indicate that you are applying for an advertised studentship competition, using the reference code iCASE. Please indicate clearly that you are applying for this project (as it is part of wider program of five such awards). You will need to provide a CV outlining your academic achievements and relevant experience, and a personal statement (500 words max) detailing your interest and fit for the studentship. Note that no project proposal is required for the iCASE studentship applications.

If you wish to apply for a combination of iCASE and other projects within the administering department (the Department of Biochemistry), this can be done on the same application form (3 projects max). If you wish to apply for both the iCASE projects and other projects within other departments, you will have to make separate applications directly through those departments in addition to your iCASE application.

If you have any specific queries about the iCASE application process, please email mrc@medsci.ox.ac.uk

More details can be found here: https://www.medsci.ox.ac.uk/study/graduateschool/mrcdtp/icase2019

All applications must be received by the deadline of 12 noon (UK time) Friday 11 January 2019.

We expect to interview shortlisted applicants in February and to make offers by the end of February.

 


 

College Scholarships

There are no College Scholarships currently being advertised

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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