PhD Studentship: Intestinal Enzymes at the Interface of Nutrient and Xenobiotic Metabolism (RUBY_U18FMH)

University of East Anglia - Norwich Medical School

Start Date: October or July 2018

Supervisor: Dr Max Ruby

Project description: A PhD opportunity is available in the vibrant and multi-disciplinary Dept of Nutrition & Preventive Medicine at Norwich Medical School. Excess weight dramatically increases a person’s risk of developing numerous ailments, including cardiovascular disease and Type 2 Diabetes Mellitus (T2DM). Gastric bypass surgery is currently among the most effective treatment options for T2DM, but its high cost may limit its widespread use. Many of the metabolic benefits occur prior to significant weight loss highlighting the therapeutic potential of altering intestinal physiology (1).

Intestinal metabolism and inflammation have emerged as early-drivers of the metabolic syndrome. Impaired duodenal nutrient signalling in obesity promotes aberrant glucose production and T2DM (2). This project will use a translational approach to uncover molecular regulators of intestinal metabolism in obesity and T2DM. We recently identified the intestinal carboxylesterase, carboxylesterase 2 (CES2), as a triglyceride lipase with powerful glucoregulatory and anti-inflammatory effects (3). CES2 is a member of the serine hydrolase superfamily. Several serine hydrolases have already been successfully targeted in the treatment of T2DM and murine models demonstrate that intestinal serine hydrolases, including CES2, are altered in obesity (4,5). Notably, CES2 and other serine hydrolases both break down and are inhibited by xenobiotics, including commonly consumed medicines and environmental chemicals.

We will determine the role of intestinal CES2 and other serine hydrolases in the development of metabolic disease.  This work will be carried out in patient material and sophisticated in vitro models of intestinal function. Analyses will include metabolic flux, standard molecular biology techniques, and chemical biology approaches. Particular emphasis will be based on potential disturbances of intestinal metabolism by xenobiotics modifying serine hydrolase activity. This PhD project will benefit from interaction with the extensive research facilities and expertise at Norwich Research Park. Informal enquiries are welcomed to Dr. Max Ruby (M.Ruby@uea.ac.uk).  

Person specification: Acceptable first degree: Biological Sciences, Chemistry, Medicine, Toxicology, Pharmacology, Physiology. The standard minimum entry requirement is 2:1

Funding notes: This PhD studentship is funded by the Faculty of Medicine and Health Sciences. Funding comprises Home/EU fees, an annual stipend (currently £14,553) and £1000 per annum to support research training.  Overseas applicants may apply but are required to fund the difference between home/EU and overseas tuition fees (in 2017/18 the difference is £13,805 for Norwich Medical School but fees are subject to an annual increase).

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Type / Role:

PhD

Location(s):

South East England