AstraZeneca/Pharmacology 4 year PhD studentship 2019, University of Cambridge, UK

AstraZeneca/Pharmacology 4 year PhD studentship applications now open : Neuronal signalling of nutrients from mouse and human intestine

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 (Neuroscience and Physiology). 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 2019.

Project available

Neuronal signalling of nutrients from mouse and human intestine

Supervisors: Dr. David Bulmer (Pharmacology)

Project description The stimulation of vagal afferent fibres by gut hormones released from enteroendocrine cells in response to nutrients, is an important mechanism in the control of food intake and gut function. Therapeutically, the activation of this pathway by delivery of nutrients into the distil intestine is key to the improvement in body weight seen following bariatric surgery in obese patients, and so replicating these events in the form of a pill is of great clinical interest. We believe that the manipulation of receptors and ion channels co-expressed by vagal afferents sensitive to gut hormones is one way of achieving this goal. To study this further, we have recently established an ex-vivo tissue preparation of the terminal ileum and ascending colon (the two major sites of nutrient signalling implicated in the success of bariatric surgery) demonstrating robust afferent responses to prototypic appetite regulating hormones (e.g. CCK and PYY), markers of vagal afferent subpopulations (e.g. neurotensin), and nutrients such as peptones. We believe this ex-vivo model offers a unique opportunity to study enhanced neuronal signalling in response to nutrient ingestion in the gut and can be readily translated by studies using isolated human tissue. The aim of this studentship will therefore be to develop this model by a) characterising the expression of receptors and channels expressed on different vagal afferent fibre populations innervating the terminal ileum and proximal colon, b) investigating the functional consequence of manipulating different receptors and channels on vagal afferent signalling in response to nutrients, and c) extending these observation into ex-vivo preparations of human gut.

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