Understanding the Mechanism of Action of Novel K2P K+ Channel Inhibitors - Potential Therapeutics for the Treatment of Neurodegenerative Disorders

This DPhil (PhD) studentship presents an excellent opportunity for world-class graduate training in the area of ion channel structural biology, biophysics, biochemistry, and drug discovery. Overall, membrane protein structure, biophysics and function form a major strategic research theme at the University of Oxford, and so provides an exciting and stimulating environment for research students in these areas.

The student will be involved in an exciting multidisciplinary project aiming to determine the basic structural and molecular mechanisms of a range of novel inhibitors of the THIK1 K+ channel. These have been developed by our industrial partner, Cerevance, a private drug discovery and development company based in Cambridge, UK. They are focused on developing novel therapeutics for central nervous system (CNS) diseases, especially Alzheimer's Disease and other neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS).

The project will provide an opportunity to learn from a range of experimental techniques (membrane protein expression and purification, nanobody production, and structural biology techniques including x-ray crystallography and cryo electron microscopy), as well as methods involved in the functional analysis of channel regulation by small molecules (ion channel electrophysiology, membrane biophysics, and pharmacology), and/or computational and molecular simulation approaches to the study of channel function. It will also allow the successful candidate to gain direct experience of working with a major pharmaceutical company.

The student will be based in the new Kavli Institute for Nanoscience Discovery in Oxford, but will also interact closely with the industrial supervisor at Cerevance who can provide access to a variety of novel tools, expertise and resources not normally available in a standard academic environment. It is also expected that the student will spend periods on secondment with Cerevance during the course of this project.

Importantly, the student will also have the opportunity to benefit from the training and networking opportunities available as part of the Interdisciplinary Bioscience DTP.