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Studentships

 

AstraZeneca/Pharmacology 4-year PhD studentships

Applications are invited for 4-year PhD studentships funded by AstraZeneca and the Department of Pharmacology. The students will be working on collaborative projects co-led by departmental supervisors and AstraZeneca scientists. Apart from carrying out their research, in their first year, the students will have compulsory training in: 1) Statistics, 2) Analysis of Biological Data and 3) Systems Training in Maths, Informatics, Statistics and Computation Biology (SysMIC). The students will join a vibrant research community of PhD students and scientists working on various research themes such as; Cell Signalling, Cancer and Infectious Diseases, Macromolecular Structure, Neuropharmacology and Vascular Pharmacology.

Candidates

We are looking for highly motivated, enthusiastic individuals, capable of thinking and working independently. Applicants should have or shortly expect to obtain a minimum of a UK II.i Honours Degree (or equivalent) in Pharmacology or a related subject including Cellular or Molecular Biology and Biochemistry. Competition is intense and successful applicants are expected to demonstrate high academic achievements. These positions are open to UK citizens or EU students who meet the UK residency requirements (home fees)

Funding

Full funding covering the University Composition Fee and Maintenance (currently £17,000 pa), is provided for up to 4 years, with effect from 1 October 2021. A maximum of four studentships will be awarded in this application round.

Project available;

Structure-guided discovery of novel small molecule inhibitors of Neuropilin-1 (NRP1)

Supervisor: Dr Taufiq Rahman (Pharmacology)

Project description

Neuropilins are a family of transmembrane proteins that are highly expressed in endothelial cells (ECs), upregulated in various tumours and they serve as cell surface co-receptors for vascular endothelial growth factors (VEGFs) and several other growth factors. The ability of Neuropilin- 1 (NRP-1) to bind to and augment the action of some growth factors are consistent with its emerging role as an oncoprotein acting by a number of mechanisms. The latter include enabling tumours to evade the immune surveillance through affecting the function of macrophages  and regulatory T cells (Tregs); promoting angiogenesis, lymphangiogenesis and cancer stemness through promotion of VEGF-A signalling in the ECs and consequently promoting tumour growth and migration. Besides, many reports suggest a direct role of VEGF NRP-1  interaction in tumour cell survival and proliferation. Therefore, quite legitimately NRP-1 has emerged as a potential target towards developing novel anti-cancer drugs. It is also very intriguing to note that the furin-cleaved product of SARS-CoV-2 spike protein also binds to the canonical VEGF-A binding site on NRP-1 and such interaction seems to critically underlie SARS-CoV-2 infectivity. Thus NRP-1 could also be a potential target towards developing novel anti-viral agent against relevant pandemic diseases. To date, there has been some attempts towards pharmacologically interfering with the interaction of NRP-1 with VEGF-A through antibodies, peptides and a few peptidomimetic small molecules. All these agents have been shown to wedge into a pocket (the so called 'tuftsin site) on NRP-1 b1 domain that recognises  a C-terminal arginine residue of VEGF-A. Few studies so far have provided us with encouraging evidence that this pocket is chemically targetable and inhibitors binding to this pocket could manifest significant inhibition of angiogenesis, tumour growth and migration in vivo.

            This project aims at structure-guided identification of novel small molecule scaffolds that will specifically bind to the abovementioned pocket and frustrate NRP-1 and VEGF-A interaction. To date, several apo and inhibitor-bound 3D structures of  NRP-1 are available. We will exploit these structures and perform in silico screening of drug/lead like libraries to identify novel chemical scaffolds as potential hits. The latter will be then evaluated experimentally using suitable biophysical (e.g. thermal shift/isothermal calorimetry) and biochemical and functional (cell-based) assays. With potential hit(s) from initial screening, elucidation of the structure activity relationship (SAR) will also be pursued. Finally attempts will be made to solve the 3D structure of NRP-1 b1 domain with the best inhibitor(s) found in this study using X-ray crystallography. Students keen to work at the interface of chemistry and biology as well as drug design are particularly welcome to apply. Prior experience in protein expression and purification with/without in silico methods will be advantageous but not an absolute requirement.

How to apply

All applications will need to be made through the University Application Portal: https://www.graduate.study.cam.ac.uk/courses/directory/blphpdphc/apply

for further information about the programme and to access the Applicant Portal. Please note that the course code for PhD applications to Pharmacology is BLPH22. Whilst making your online application please make clear that you are applying for AZ funding. Your online application will need to include:

  • Two academic references  
  • Transcript  
  • CV/resume
  • Evidence of competence in English   
    If required - you can check using our tool
  • Statement of interest (1500 characters)
  • Application cost £70 (you have 3 applications)

 

Informal inquires about individual projects should be directed to the supervisor listed above.

Applications need to be submitted by 14th March 2021 by midnight. Applications will be assessed as and when they are submitted. Interviews will take place w/c 22nd March 2021.

Please quote reference PL25679 on your application and in any correspondence about these positions.

The University values diversity and is committed to equality of opportunity

 

 

 

Dr David James Studentship

davidjamesBW

During his life, Dr James was a well-respected Departmental Administrator. His legacy provides scholarships for the most gifted postgraduates to pursue focused and original research. The David James Studentship has provided full financial support for a number of PhD students within the Department since October 2011.

Via PhD studentships, the David James Fund is supporting the next generation of Cambridge pharmacologists, whose work will be crucial to developing better treatments for diseases such as cancer, cardiovascular disease, arthritis, diabetes and Crohn's disease.