The deadline for applications is 5pm on Friday 23rd November 2018.
2nd supervisor, Dr Emily Henderson (Bath), 3rd supervisor Prof Jack Mellor (Bristol)
Parkinson’s disease is a neurodegenerative condition that affects many parts of the brain leading to cognitive and motor deficits. This project aims to investigate the interaction between cognitive and motor functions and the brain circuits that mediate them to provide novel targets for therapeutic symptomatic intervention.
Cognitive and other non-motor deficits in Parkinson’s have significant, negative impacts on quality of life in excess of the classically described motor phenotype. It is becoming increasingly clear that cognitive deficits interact with motor dysfunction to e.g. precipitate falls. In a recent phase II clinical trial by one of the supervisory team (Henderson) it was shown that administration of a cognitive enhancing acetylcholine esterase inhibitor (AChEI) reduced falls in patients with PD by 40%. Since these falls are often caused by distraction when attention is divided, enhancing the cognitive and attentional capacity may improve motor control. However, we know very little about the mechanisms that mediate this interaction between cognitive and motor functions.
PD is a neurodegenerative disease characterised by specific degeneration of dopaminergic and cholinergic neurons associated with aggregation of protein plaques. The motor symptoms associated with PD may to be partially ameliorated by dopamine replacement strategies but the cognitive symptoms have no treatment other than AChEIs. This suggests that the motor symptoms of PD are caused by hypodopaminergic function whereas the cognitive symptoms are caused by hypocholinergic function. However, there is likely a complex interaction between the two systems and understanding these mechanisms will be crucial to develop new strategies to treat the cognitive symptoms of neurodegeneration in PD.
This project will investigate the underlying mechanisms using animal models of dopaminergic and cholinergic hypofunction coupled with novel clinically informed behavioural tests that combine cognitive and motor components. These tasks have been developed in a collaboration between the Robinson and Henderson groups to measure footslips and falls in response to presentation of distractors as a model of falls in humans. Dopaminergic and cholinergic hypofunction will be induced chronically or acutely using genetic approaches to manipulate dopaminergic and cholinergic neurons. These opto- and chemo-genetic techniques have been developed and validated in the Mellor group. The ultimate goal will be to develop novel pharmacological approaches to enhance function and to test the effects in a neurodegenerative model.
The student will be trained in animal behavioural paradigms and genetic manipulation of neuronal subtypes and related molecular techniques. The student will also benefit from working at the interface between clinical and basic research in a project based on a back-translational approach. In addition, through longstanding collaborations with computational neuroscientists Conor Houghton, Cian O’Donnell and Krasimira Tsaneva-Atanasova in Bristol and Exeter the project can also be extended to use computational models to predict the likely interactions between cognitive and motor systems.
Please complete an application to the GW4 BioMed MRC DTP for an ‘offer of funding’ DO NOT APPLY to the University of Bristol, only do this if you're successful in being awarded funding from GW.4’. Please see: View Website
Funding is for 3.5 years; to be eligible for a full award (fees and stipend) from a Research Council, a UK or EU student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship. Further details on eligibility: View Website
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