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iCASE projects (October 2018 entry)

Project 1


Fundamental properties and functional plasticity of a spinal dorsal horn circuit and its role in neuropathic pain

Warwick supervisor: Prof. David Spanswick (d dot c dot spanswick at warwick dot ac dot uk)

Industry partner: Neurosolutions Ltd

Industry supervisor: Dr Andrew Whyment

Chronic pain has been described as “like a silent epidemic”, affecting an overwhelming number of people. Current therapies are inadequate, in part reflecting our lack of understanding of the mechanisms underlying chronic pain. Here we will work in collaboration with NeuroSolutions Ltd to characterise a distinct group of nerve cells in the spinal cord: identify the mechanisms that regulate their electrical excitability, the chemical messengers they produce and their role in modulating pain, in particular neuropathic pain states. Through an understanding of the role of these nerves and the factors that regulate their function, we aim to design new, improved therapeutic approaches to treat neuropathic pain.

Project 2


New prognostic and diagnostic tools to assess and monitor traumatic brain injury

Warwick supervisor: Prof. Nicholas Dale (n dot e dot dale at warwick dot ac dot uk)

Industry partner: Sarissa Biomedical Ltd

Industry supervisors: Prof. Chris Imray (University Hospitals of Coventry and Warwickshire and Dr Everard Mascarenhas, Sarissa Biomedical Ltd)

Over 1.4 million patients attend hospital suffering from a traumatic brain injury (TBI) annually, and UHCW is one of the busiest trauma centres in the UK. Risk scores are often used as a way of predicting a patient’s chances of survival after injury. This is important information for clinicians, patients and family in the immediate setting. However, for patients who survive, there is a need for a score that predicts a patient’s recovery, and how much rehabilitation and support they might need after discharge. This project has been designed to look at novel specific measures of brain metabolism, damage and recovery to develop a new recovery prediction model following TBI. The collaboration between UHCW and Sarissa will provide a unique opportunity to validate and research the applicability of cutting-edge markers of brain injury, ultimately leading to information to improve patient care, and help clinicians care for patients with TBI.

Project 3


Mechanistic understanding to inhibitors of peptidoglycan glycosyltranferases

Warwick supervisor: Prof. David Roper (david dot roper at warwick dot ac dot uk

Industry partner: LifeArc

Industry supervisors: Dr Cathterine Kettleborough and Dr Andrew Merritt

The biosynthesis of the bacterial cell wall is a complex process, coordinated with cell division, which we are only just starting to understand at a molecular level. Since most of the key proteins are either membrane bound or membrane associated this has been a difficult area to access and study in the past. Recently there has been a renaissance in the techniques, tools and methods to study bacterial cell biology that provides for basis for both new biological understanding but also translational application. In this project, we will apply tools of drug discovery to one of the most fundamental aspects of cell wall biosynthesis: the polymerisation lipid II by glycosyltranferase enzymes. By applying a mixture of structural biological insight with enzyme mechanistic understanding and modern approaches to chemical design we hope to produce new chemical probes that will interrogate the biology of these crucial cell wall biosynthetic enzymes.

Project 4


Statistical design and analysis of clinical studies using personalised healthcare under biomarker uncertainty

Warwick supervisor: Dr Deepak Parashar (d dot parashar at warwick dot ac dot uk)

Industry partner: Roche Pharmaceuticals

Industry supervisor: Dr Chris Harbron

In collaboration with Roche, the PhD project will address an important issue on the role played by continuous biomarkers in the identification of patients most likely to benefit from a particular treatment within the setting of Personalised HealthCare. In order to identify cut-­offs that define the targeted subgroup of patients, novel statistical and machine learning methods will be used on large datasets from clinical trials. The research problem shall form a crucial part of the biomarker-­driven drug development programme from a pharmaceutical industry perspective. A unique opportunity is, therefore, available for embarking on a challenging biomedical statistics research area in a pan academic-industry environment via the MRC iCASE studentship as part of the Warwick DTP in Interdisciplinary Biomedical Research. This project will suit a student with a good undergraduate degree in statistics or a related discipline.