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Studentships

Please click on the below links to go directly to the desired studentship:

 

1.   AstraZeneca/Pharmacology 3 and 4 year PhD studentships (ref: PL13822)

2.   BBSRC iCASE Award PhD Studentship with Cairn Research (ref:PL13852)

3-   Development of Next-Generation Antibiotics (ref: PL13917)

4-   BBSRC-funded iCASE studentship with LifeArc (ref: PL13916)


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 2018. A maximum of four studentships will be awarded in this application round.

The University of Cambridge is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

AstraZeneca/Pharmacology 3 and 4 year PhD studentships

1) Targeting growth factors to treat visceral pain (4 years)

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There is an increasing unmet clinical need for effective, non-opioid based pain killers. Few novel analgesic mechanisms have been progressed in decades, while addiction to opioids is a major and growing burden on society. Drugs targeting neurotrophins, in particular nerve growth factor (NGF), may be one solution to this problem. NGF is strongly implicated in inflammatory pain pathology, and clinical studies with anti-NGF antibodies have shown robust efficacy in patients with painful osteoarthritis.
Chronic abdominal pain from the gastrointestinal tract is a common problem affecting up to 15% of the UK population, however the therapeutic potential of anti-NGF therapies for the treatment of abdominal pain in diseases such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) has not been fully explored, and are the objective of this studentship. To study these further, we will utilise human tissue assays (biopsy and surgically resected tissues) to examine the role of NGF and other growth factors in the activation of the pain sensing nerves within the gut (visceral nociceptors) during IBS and IBD. Additionally, we will also explore the role of cytokines, key mediators of immune function, in the activation of visceral nociceptors during gastrointestinal disease, paying particular attention to possible synergistic benefits from the blockade of specific cytokine/growth factor pairings. Students are directed to recent publications Hockley et al (2014) & McGuire et al (2016) from my lab highlighting the use of these approaches to study human visceral nociception in gastrointestinal disease

McGuire et al (2016) Ex vivo study of human visceral nociceptors. Gut epub.
Hockley et al (2014) Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease-derived stimuli. Pain, 155(10):1962-75


2) An in vitro model of inflammatory bleeding (4 years)


Platelets play a key role in haemostasis by aggregating to stop bleeding at sites of vessel injury. However, in thrombocytopenia, spontaneous bleeding is seen in some patients but not in others. Similarly, drugs that inhibit platelet function lead to bleeding in some patients but not others. One recent hypothesis to explain this is that platelets prevent inflammatory bleeding. In thrombocytopenic mouse models, local inflammation triggered rapid bleeding in the microvasculature of the skin, lung or brain. Conversely, no bleeding was seen in mice with normal platelet counts, or in thrombocytopenic mice in the absence of inflammation. In this inflammatory bleeding paradigm, single platelets inhibit or repair the damage caused by neutrophil extravasation and activation. This role is independent of the platelets ability to aggregate, which means that it is not predicted by tail bleeding time, the current standard measure of haemostasis in mice and rats. In this project we will create an in vitro model of inflammatory bleeding, to better understand the mechanisms involved and to help predict whether bleeding may be a side-effect of drug action. This model will combine microfluidics, endothelial cell culture, and perfusion of isolated platelets, leukocytes or whole blood.  The in vitro model of inflammatory bleeding will be used to answer questions such as, how do platelets prevent inflammatory bleeding, which platelet receptors and functional responses are necessary, and how might drug action on platelets, neutrophils or endothelial cells promote or prevent inflammatory bleeding? This knowledge is of relevance both to potential treatment of bleeding in thrombocytopenia, but also in understanding causes of bleeding as an effect of drug treatment.

3) Rational development of small molecules that can inhibit both PARP and an additional protein target of the angiogenesis pathway (4 years)


Poly(ADP-ribose) polymerase (PARP) inhibitors are an emerging class of drugs that inhibit PARP-1 and PARP-2 proteins, which play a critical role in base excision repair (BER). When PARP function is impaired, double-stranded DNA breaks accumulate in the absence of effective BER and in cells that lack efficient homologous recombination capabilities (such as those harbouring mutations in tumour suppressors BRCA1/2, ATM etc.), these breaks cannot be accurately repaired, resulting in synthetic lethality. This has been supported by preclinical studies that PARP inhibition could indeed induce synthetic lethality in tumours with inherited, incapacitating mutations in BRCA1 or BRCA2 that are associated with high grade ovarian cancer and triple negative breast cancer. Interestingly, several studies have shown that genetic or pharmacological inhibition of PARP-1 could also induce suppression of angiogenesis. Therefore, a clinically-exploitable synergy can be anticipated for the combined use of PARP-1 inhibitors and anti-angiogenic agents (for e.g. anti VEGF or anti VEGF receptor) against ovarian and triple negative breast cancer. In this project, we propose to rationally develop small molecules that will selectively inhibit PARP1 as well as another valid target within the angiogenesis pathway such as the VEGF receptor or the store-operated calcium entry channels. The student will make extensive use of various ligand and structure-based in silico approaches complemented with relevant biophysical (e.g. thermal shift/isothermal calorimetry), biochemical and functional (cell-based) assays. With potential hit(s) from initial screening, elucidation of the structure activity relationship (SAR) will also be pursued.


Applicants should minimally have (or expect to obtain) the equivalent of a UK first class or upper second-class honours degree in a relevant discipline in the natural sciences (e.g. chemistry, pharmacology, biochemistry, bioinformatics). We particularly welcome applications from students interested in working at the interface between biology and chemistry. Some background in protein purification/biochemical techniques with/without in silico methods will be advantageous.

 

4) Unravelling the mechanisms regulating GLP1 receptor internalization and recycling in insulin secreting pancreatic ß-cells (4 years)

BBSRC-funded iCase studentship with AstraZeneca

Therapies targeting insulin secreting ß-cells for the treatment of type 2 diabetes (T2D) remain an unmet medical need because there are no approved therapies that reverses loss of functional ß-cell mass, the primary defect leading to disease progression in T2D. Biologics offer great promise as regenerative treatments, for example antisense oligonucleotides [ASO] can knockdown currently undruggable genetic targets or transcription factors linked to ß-cell loss in T2D. Recently our collaborators at AZ has shown, in vitro and in vivo, that conjugation of ASOs to a peptide agonist based upon GLP-1 (an insulinotropic gut hormone) is an unexpected and remarkably effective approach to specifically deliver ASO-cargo to pancreatic ß-cells. While novel, exciting and therapeutically important, as yet, we do not understand the underlying biology related to GLP-1 receptor endo/exocytosis in ß-cells although accessory proteins such as ß-arrestin proteins are expected to play a role. Thus we will use multidisciplinary approaches (pharmacology, cell imaging and computational biology) to quantitate and improve the rates of GLP-1-ASO uptake via the GLP-1 receptor recombinant cell lines and native pancreatic ß-cells.

This studentship is offered as part of the BBSRC DTP Programme (http://bbsrcdtp.lifesci.cam.ac.uk/). The student will complete tailored training courses, a PhD and have the opportunity to spend time with the industrial Partner, AstraZeneca. The Programme organises a number of events, training courses and workshops to foster cohort development, skills enhancement and networking opportunities.

5) Studying the function of BCL11A interaction with the SWI/SNF complex in TNBC (3 years)


The Khaled lab recently reported the finding of one such gene, called BCL11A (Khaled W.T. et al Nat Comm 2015). The Khaled lab analysed both METABRIC and TCGA cancer genomics datasets and found that the transcription factor BCL11A was overexpressed in the majority of TNBC/BLBC’s and that its genomic locus was amplified in up to 38% of these tumours. Moreover, analysis of the TCGA data revealed that the BCL11A locus was hypo-methylated almost exclusively in BLBC tumours but not other subtypes. The Khaled lab also showed that exogenous BCL11A overexpression promoted tumour formation, whereas its knockdown in TNBC cell lines suppressed their tumorigenic potential in xenograft models. We showed that in a mouse DMBA-induced tumour model, Bcl11a deletion substantially decreased tumour formation, even in p53-null cells and inactivation of Bcl11a in established tumours caused their regression. This suggests that developing anti-BCL11A drugs could be used for TNBC-targeted therapy, however, its essential roles in immune cells might disadvantage direct inhibition approach. Therefore, it is important to understand how BCL11A protein-protein interactions are different in the cancer cells vs. normal cells. This project will focus on the study of the SWI/SNF chromatin-remodelling complex and it’s interaction with BCL11A in TNBC. The project will utilise a combination of biochemical, proteomic and genomic analyses. Any prior experience in these areas will be beneficial.

Please send the following to ()
Your CV (max two A4 pages), with full contact details of 2 academic referees.
A covering letter (max two A4 pages) highlighting (a) your research interests and relevant experience and (b) what you hope to achieve from the programme. You should also state in order of preference which two projects you would like to be considered for.
Informal inquires about individual projects should be directed to the supervisors listed above.


Applications need to be submitted by 5pm (GMT) on 14th Dec 2017. Applications will be assessed as and when they are submitted. Interviews will take place between 15th and 31st, January 2018.

Please quote reference PL13822 on your application and in any correspondence about these positions.

 

BBSRC iCASE Award PhD Studentship with Cairn Research (fixed term)

Analyses of calcium signalling pathways using advanced optical imaging and genetically encoded sensors


Applications are invited for a PhD studentship in the laboratory of Prof Colin W Taylor in the Department of Pharmacology, University of Cambridge to explore mechanisms of calcium signalling using advanced optical imaging methods. The project will be in association with Cairn Research Ltd (www.cairn-research.co.uk), which will provide first-hand experience of design and development of fluorescence microscopes. The specific project and placements with Cairn will be tailored to the interests of the successful candidate and can thereby accommodate students with backgrounds in the physical or life sciences. Further information is available from recent publications (Thillaiappan et al, Nat Comm. In press; Cell Reports 18, 711-; Nature 483, 108-) and our web site: https://www.phar.cam.ac.uk/research/taylor

Many stimuli control cellular activity by regulating the opening of Ca2+ channels. The lab is interested in IP3 receptors, which are intracellular Ca2+ channels that control Ca2+ release from the ER and, through store-operated Ca2+ entry, influx of Ca2+ across the plasma membrane. Regulated opening of these Ca2+ channels causes an increase in cytosolic Ca2+ concentration that controls many cellular activities, but Ca2+ passing through open IP3 receptors can also be directed to other intracellular organelles, notably mitochondria and lysosomes. This allows these organelles to accumulate Ca2+, which can then regulate their activities. Hence, IP3 receptors are the conduits through which Ca2+ within the ER can be redistributed to the cytosol or to other intracellular organelles. Many of these interactions occur at membrane contact sites, where two organelles are held together by tethering proteins forming junctions that facilitate communication between them. This project, in collaboration with Dr Steve Tovey at Cairn Research, will use genetically encoded Ca2+ sensors and additional tools to explore, using high-resolution optical microscopy, IP3 receptor regulation and interactions between the ER and other intracellular membranes.

Applicants must have or expect to obtain at least an upper 2nd class honours science degree (or equivalent). The appointee will be motivated, capable of developing his or her own ideas, and keen to interact effectively with other lab members. The studentship is for up to 4 years and will provide a stipend at the standard Research Council rate, college and university fees, and a travel allowance. Funding is available only for UK or EAA students who meet the UK residency requirements. The start date is October 1, 2018. Informal enquiries to .

Applications must include a CV (including past exam results), the names and contact details of 2 academic referees, and short statement (no more than 350 words) describing your interest in the project. Applications must be sent to pharsect@hermes.cam.ac.uk to arrive no later than 5pm on December 7, 2017.  Interviews of short-listed candidates are likely to be held between December 18 and 20.

Please quote reference PL13852 on your application and in any correspondence about this vacancy.

Development of Next-Generation Antibiotics



The introduction of antibiotics was a turning point in the history of medicine and has saved countless lives. Unfortunately, the use of these wonder drugs is accompanied by the emergence of antibiotic resistant pathogenic bacteria, which are difficult to eradicate.

A BBSRC Doctoral Training Programme-funded PhD position is now available up to 4 years in the Department of Pharmacology, University of Cambridge, in the research group led by Dr Hendrik van Veen. This project will focus on the ATP-binding cassette exporter MsbA, the activity of which is essential for outer membrane biogenesis and viability of many Gram-negative pathogenic bacteria including Escherichia coli, Salmonella spp., Pseudomonas aeruginosa, Vibrio cholerae, Klebsiella pneumoniae, Yersinia pestis and Acinetobacter baumannii. To develop next-generation antibiotics, we aim to disrupt growth of these bacteria by generating novel selective inhibitors of MsbA.

Applicants should be highly motivated, enthusiastic individuals, capable of thinking and working independently, and should have outstanding presentation and writing skills. Furthermore, applicants should have or shortly expect to obtain a minimum of a UK II.i Honours Degree (or EU equivalent) in Pharmacology, Biochemistry, Chemistry or a related subject. Experience in biochemical and functional analyses of proteins and/or chemical synthesis would be very useful. Competition is intense and successful applicants are likely to demonstrate high academic achievements. The start date is October 1, 2018.

Applicants should have or shortly expect to obtain a minimum of a UK II.i Honours Degree (or EU equivalent) in Pharmacology, Biochemistry, Chemistry or a related subject. Competition is intense and successful applicants are likely to demonstrate high academic achievements.

Candidates should submit a C.V., a brief supporting statement (two sides maximum), a list of publications, including the names and addresses of two referees, to pharsect@hermes.cam.ac.uk to arrive no later than 5pm on December 15, 2017.

Further information can be found on our website at: http://www.phar.cam.ac.uk/research/vanveen

Please quote reference PL13917 on your application and in any correspondence about this vacancy.

BBSRC-funded iCASE studentship with LifeArc (4 years)

How do matrix metalloproteinases stimulate neurones?



Applications are invited for a PhD studentship in the laboratory of Dr David Bulmer in the Department of Pharmacology, University of Cambridge to explore the role of matrix metalloproteinases in neuroimmune signalling.

This project is a CASE award with LifeArc, the new name for MRC Technology, a medical research charity with a 25 year legacy of helping scientists and organisations turn their research into treatments and diagnostics for patients. LifeArc is pioneering new ways to turn great science into greater patient impact. So far, LifeArc's work has helped to develop four drugs (Keytruda®, Actemra®, Tysabri® and Entyvio®) and a test for antimicrobial resistance.

Matrix metalloproteinases (MMPs) are a family of serine proteases implicated in tissue remodeling, fibrosis and inflammation. We have recently identified a novel role for MMP-12 as a putative mediator of abdominal pain. As part of these studies we showed that direct application of MMP-12 stimulated sensory nerves innervating mouse, and human gut, highlighting a hitherto unrecognised role for MMP-12 as an effector of neuroimmune interactions.
Following on from these observations, the goal of this studentship will be to investigate the stimulatory effect of MMPs on sensory neurons. To do this, we will begin by examining which of the many MMPs stimulate sensory neurons innervating the gastrointestinal tract. In addition, as the gut is innervated by different populations of sensory nerves that sub-serve distinct physiological functions based on anatomical and molecular (receptor and channel expression) specialisations. A secondary goal of these studies will therefore be to determine which sensory nerve subtype is stimulated by a specific MMP, paying particular attention to sensory nerves implicated in the perception of noxious or painful stimuli (nociceptors). Finally, we will also investigate the specific mechanism by which MMPs stimulate sensory nerves, before looking to translate our findings in mouse tissue to human by recording activity from sensory nerves innervating the human gut.

Applicants must have or expect to obtain at least an upper 2nd class honours science degree (or equivalent). The appointee will be motivated, capable of developing his or her own ideas, and keen to interact effectively with other lab members.
The studentship is for up to 4 years and will provide a stipend at the standard Research Council rate, college and university fees, and a travel allowance. Funding is available only for UK or EAA students who meet the UK residency requirements. The start date is October 1, 2018. Informal enquiries to

Applications must include a CV (including past exam results), the names and contact details of 2 academic referees, and short statement (no more than 350 words) describing your interest in the project. Applications must be sent to pharsect@hermes.cam.ac.uk to arrive no later than 5pm on December 14, 2017.  Interviews of short-listed candidates are likely to be held January 2018.

BBSRC DTP Programme
The studentship is part of the BBSRC DTP Programme (http://bbsrcdtp.lifesci.cam.ac.uk/).  The student will complete tailored training courses, a PhD and have the opportunity to spend time with the industrial Partner, LifeArc. The Programme organises a number of events, training courses and workshops to foster cohort development, skills enhancement and networking opportunities

Please quote reference PL13916 on your application and in any correspondence about this vacancy.

The University of Cambridge is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

 

Dr David James scholarships

davidjamesBWDuring his life, Dr David 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 Parkinson's.