Diabetic neuropathy is a common secondary complication of diabetes mellitus which affects around 50% of all patients with diabetes - impacting on health, wellbeing and quality of life. Symptoms of diabetic neuropathy arise in a typical ‘glove and stocking’ distribution, with the longest axons of the body showing distal die-back of terminals from the skin of the feet and hands. Innervation of the skin is through both autonomic and sensory fibres. Sensory afferents in the skin are activated by physical touch, temperature and/or chemical stimuli and autonomic efferents regulate glandular activity and vasoregulation. Patients with diabetic neuropathy typically develop symptoms such as pain, tingling, burning or aching sensations or numbness. Loss of sensation can lead to tissue damage and an increased risk of limb amputation
The underlying origin of the disease is complex and poorly understood. Our current work uses untargeted proteomic and metabolomic analysis of various regions of the nervous system, including sciatic nerve, trigeminal and dorsal root ganglia, to identify proteins and metabolites whose levels alter in diabetes. This approach has allowed us to generate new hypotheses regarding the mechanisms underlying diabetes-associated neuropathy. This PhD project will both extend these studies into different regions of the nervous system and examine the impact of modulating key target proteins/pathways on nerve function using in vivo and in vitro models of sensory nerve regeneration. Gaining further understanding of the pathogenic changes that occur in disease and how these impact on nerve phenotype will play a major role in providing new targets for treatment of diabetic neuropathy.
This multidisciplinary project aims to improve our understanding of the contribution of lipids on distal axon degeneration of sensory neurons in diabetic neuropathy. We have established experimental models of diabetic neuropathy. The student will learn a variety of important experimental skills from working with rodents, tissue dissection and immmunohistochemisty, and in vivo behavioural assessment of sensory nerve function (thermal and mechanical sensitivity threshold, nerve conduction velocity measurement), and ‘omics analysis of tissue. These studies will be combined with in vitro experiments to investigate the axon outgrowth dynamics of sensory neurons prepared from adult rat dorsal root ganglia.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject.
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Neuroscience
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk