Medicine

*BBSRC EASTBIO Programme* The Role and Utility of Exosomes as a Biomarker of N-Methyl-D-Aspartate Receptor Encephalitis

Introduction

IgG autoantibodies to N-methyl-D-aspartate (NMDA) receptor GluN1/2 subunits stimulate an autoimmune neuroinflammatory state in NMDA receptor encephalitis (NMDARe)1. Patients present insidiously, with changes in behaviour, but subsequently develop psychotic features and movement disorders. Hypoventilation and coma can necessitate critical care support. The first case diagnosed at Ninewells Hospital was in 2011, in a patient with ovarian teratoma (teratomas are present in around 60% of cases).

*BBSRC EASTBIO Programme* Is there a role for GABA-A receptor alpha-5 subunits in cognitive deficits caused by consumption of a high fat diet?

Project Synopsis: This project will use dietary manipulations in mice and look at behavioural effects on memory alongside electrophysiological changes in synaptic plasticity and changes in receptor expression in the brain. It will investigate the question of whether GABA-A receptor alpha-5 subunits, a target for cognitive enhancing drugs, are upregulated by a high fat diet and whether this is linked to inflammatory cytokine activation. It aims to define a mechanistic link between fat consumption and memory loss.

*BBSRC EASTBIO Programme* Development of biomechanically musculoskeletal models and its application in understanding of ageing process for health

The ageing process in health is one of main research topics currently and in the near future. The key icon for ageing in health is daily movements, e.g. walking. Sometime, people are unable to walk as normal because of various reasons, e.g. for the ageing in the elderly. As gait change indicates the ageing process, and thus it is important to look into how walking changes. So far, the updated motion capture system is capable of investigating gait in detail, e.g.

*BBSRC EASTBIO Programme* Development of a microscopy-based method for monitoring domain flexibility of macromolecular complexes in living cells

The biological activities of macromolecular complexes involve dynamic movements of their domains or subunits, but the kinetics of such motions in the cellular environment are mostly unknown due the lack of suitable approaches. This project aims to develop a microscopy-based method that monitors changes in domain flexibility in real time in live cells.

*BBSRC EASTBIO Programme* Age-dependent regulation of hippocampal synaptic function by the estrogen-sensitive receptor, GPER1

In Western societies, life expectancy is steadily increasing and currently around 20% of the UK’s population is over 65. Consequently, more people are suffering from age-related disorders, such as cognitive decline and neurodegeneration. It is known that the hippocampus plays a key role in learning and memory, and hippocampal damage results in cognitive deficits similar to those experienced with aging. The hippocampus is also one of the first areas of the brain to degenerate in age-related brain disorders such as Alzheimer’s disease.

Palmitoylation and the regulation of the “funny” current HCN4 channel

Applications are invited for a PhD studentship in the laboratories of Dr Will Fuller (Division of Molecular & Clinical Medicine, University of Dundee) and Professor Jules Hancox (School of Physiology and Pharmacology and Neuroscience, University of Bristol). The project will characterise a novel regulatory mechanism of the ion channel ‘HCN4’, which controls the rate of the heart’s intrinsic pacemaker. The project will therefore provide new insights into a hitherto overlooked mechanism by which cardiac pacemaker activity could be modulated.

Personalised medicine for blood pressure and diabetes control and prevention of kidney disease.

The main reason for kidneys to fail is due to diabetes and prolonged exposure to high blood pressure.  These two factors account for nearly three quarters of all kidney disease.   The effectiveness of drugs in the management of blood pressure and diabetes is highly variable in different individuals and it would be desirable to be able to use simple tests to predict which drugs will work in particular patients.   The current project aims to define predictive markers to allow for the more effective prevention of kidney disease in patients with high blood pressure and diabetes.  The student wi

Personalised Medicine in Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now regarded as the most common liver condition in the developed world, affecting up 30% of the general population. It is closely linked with the metabolic syndrome and its component parts including obesity, type 2 diabetes mellitus (T2DM) and dyslipidaemia, with insulin resistance and excess oxidative stress being the common uniting pathological mechanisms.

The use of a novel in vitro microfluidic model to understand how neurons in a network work together to respond to a local injury.

Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients.

The use of a novel in vitro microfluidic model to understand how neurons in a network work together to respond to a local injury.

Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients.

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