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 Dr Bulmer email@example.com
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
Applications from agencies will not be considered.
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 firstname.lastname@example.org to arrive no later than 5pm on December 14, 2017. Interviews of short-listed candidates are likely to be held January 2018. If you have any questions about this vacancy or the application process, please contact Amparo Saez (email@example.com)
Please quote reference PL13916 on your application and in any correspondence about this vacancy.
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