skip to primary navigationskip to content
 

Studentships

Astra Zeneca Studentships

AstraZeneca/Pharmacology 4 year PhD studentship applications now open 

 

 

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/EU candidates only.  

 

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 2020. A maximum of four studentships will be awarded in this application round.  

 

Projects available; 

 

  1. Developing novel protein modulators against ion channels as essential pharmacological tools to probe biological function. 

 

 

Miller Bio - Paul Miller is a new lecturer in the Pharmacology Department, joined September 2018. He uses functional (e.g. electrophysiology) and structural (Cryo-electron microscopy) approaches to understand how GABAA receptors are modulated by ligands. Principal research aims of the Miller lab include: understanding protein binders and modulators, particularly antibodies, of GABAA receptors; engineering these modulators to modify function (e.g. type of modulation, positive, neutral or negative), affinity and selectivity; raising novel modulators against targets for which suitable ligands are lacking; investigating the properties of these modulators in physiological systems; and establishing methodology for systemic delivery of protein modulators into the central nervous system. 

 

Project summary 

 

GABAA and glycine receptors are the principal mediators of inhibitory neurotransmission throughout the central nervous system (CNS). In animal models and in the clinic controlling these receptors through the use of small molecule positive allosteric modulators (PAMs) alleviates symptoms of neurological disorders such as autism, generalised anxiety disorder, epilepsy, pain, insomnia, stroke and Alzheimer’s. Nevertheless, the selectivity of small molecule drugs remains unsatisfactory and many receptor subtypes lack suitable tool compounds to pharmacologically evaluate their importance in biological and disease pathways. This hinders our understanding of fundamental neuroscience and limits our ability to combat many prevalent neurological disorders. 

 

The extended contact area of protein-protein versus small molecule-protein interactions mean that antibodies overlap with subtype-specific epitopes on GABAA receptors. Single domain antibodies (nanobodies) have been identified that are highly efficacious PAMs of GABAA receptors and have high (10-1000-fold) subtype selectivity (1). Furthermore, native antibodies against GABAA receptors and glycine receptors have been identified from the sera of patients with autoimmune disorders, some of which are inhibitors. These discoveries provide proof of principle that pentameric ligand-gated ion channels represent good targets for the generation of subtype selective antibody-based binders and modulators. If raised against subtype targets currently lacking selective modulators, such antibody-based tools would make a powerful addition to the pharmacological toolkit to better understand the molecular correlates of neurological pathways. Furthermore, given the recent surge in success of clinical biologics and progress in systemic delivery technologies to target antibodies to the CNS (2), such tools represent obvious translatable targets for the treatment of neurological disorders. This work will involve production of natively folded proteins to be screened on in vitro antibody display technology platforms at Astra Zeneca, overseen by AZ collaborator, Dr Trevor Wilkinson (3). This will be carried out in the presence of relevant drugs to enforce a particular channel conformation, with the aim of raising unique tools against rare subtypes that currently lack selective modulators and are generally poorly understood. Antibodies will be screened and characterised by binding assays, electrophysiology and cryo-EM. Successful tool modulators will be tested physiologically in animal systems in house and/or by collaborators to reveal novel contributions of previously hard to target subtypes in biological pathways. 

 

References 

 

  1. Miller, P.S., et al. Heteromeric GABAA receptor structures in positively-modulated active states. Online through BioRxiv, (2018). Submitted to eLife, undergoing revision. 

  1. Williams, W.A…Wilkinson, T…Chessell, I. Antibodies binding the head domain of P2X4 inhibit channel function and reverse neuropathic pain. (2019). Pain. PMID: 31045747. 

  1. Dodd, R.B., Wilkinson, T., Schofield, D.J. Therapeutic Monoclonal Antibodies to Complex Membrane Protein Targets: Antigen Generation and Antibody Discovery Strategies. (2018). Biodrugs 32:339-355. PMID: 29934752. 

 

  1. Evolving the human taste receptors as a method to regulate blood sugar 

 

 

Project description 

 

Type II diabetes mellitus (T2DM) is a bihormonal disorder characterised by elevated blood glucose due to inappropriate levels of the glucose homeostatic hormones insulin and glucagon. Typically, a T2DM patient will secrete excess glucagon (due to the bodies inability to take up the glucose) while failing to appropriately secrete insulin. While many of these drugs show initial efficacy for the treatment of T2DM, their action is often relatively short lived. An alternative method would be to generate cells, derived from the patient’s own cells that express receptors for G protein-coupled receptors (GPCRs) that can sense glucose and tune the response such that the cells secrete insulin or glucagon dependent on the circulating glucose concentrations. In this project we will characterise the newly identified glucose responsive GPCRs (Calcium sensing receptor; CaSR and Taste receptors T1R1&T1R3)1 using large scale synthetic saturation2 mutagenesis and receptor tuning3 developing an array of glucose sensors that can detect very small fluctuations in concentrations. Initial experiments will be performed in HEK 293 cells prior to studies in Endocells and mammalian T cells. 

 

References 

 

1. Öling et al. (2018) ACS Synth Biol 7: 2317-2321. 

2. Kojima et al. (2017) Diabetes Obes Metab, 19 Suppl 1, 54-62 

3. Shaw et al. (2019) Cell 177:782-796 

 

  1. Development of a novel strategy for promoting cardiomyocyte proliferation for cardiac regeneration in adult mice 

 

Supervisor: Dr. Catherine Wilson (Pharmacology) 

 

Project description  

There are around 23 million heart failure patients worldwide, which has a major socio-economic impact. There is currently no cure for heart failure and treatments only slow disease progression. After a heart attack, an adult human heart can lose up to 1 billion cardiomyocytes, which are never replenished due to the low intrinsic regenerative capacity of the adult heart. This loss leads to diminished heart contractility, scar formation, heart failure and death. None of the current treatment options are able to reverse the degeneration of the heart tissue. Therefore the inability to regenerate the heart is a significant unmet clinical need. 

We have recently discovered that transient co-expression of Myc and Cyclin T1 (Ccnt1) are capable of reactivating cardiomyocyte proliferation in the adult mouse heart. This program will assess the effects of expressing Ccnt1 and Myc in cardiomyocytes using transient gene expression after experimental myocardial infarction in mice.  We will determine and optimise such treatment and asses if it is able to promote morphological controlled cardiac regeneration and prevent adverse cardiac remodelling.  

 

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 and the 2-principal investigators you are interested in working with. 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 £65 (you have 3 applications)   

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

Applications need to be submitted by 9th December 2019. Applications will be assessed as and when they are submitted. Interviews will take place between 3rd and 14th, February 2020. 

Please quote reference PL21290 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

The Department will not be offering a David James Studentship in 2020. 

davidjamesBWDr David James. 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.

And through 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, arthritis, diabetes and Crohn's disease.

The studentship will cover a stipend equivalent to the standard Research Council rate (£14,777 per annum for 2018/19), research costs and tuition fees at the UK/EU rate, for three years and is available for the successful UK or EU student - but please see information here regarding EU fee status for entry 2019 and onwards: https://www.graduate.study.cam.ac.uk/finance/fees