Longitudinal assessment of cognitive and behavioural phenotypes in knock-in mouse models of Huntington’s disease
PhD Research
Start Date: 1st October 2012
Funding:
The studentship is funded for 3 years by the Medical Research Council and includes payment of tuition fees and a tax free maintenance stipend for UK applicants. EU students are only eligible to have their tuition fees paid unless they have been resident in the UK for three years prior to the start date of the programme and then they are also entitled to receive the maintenance stipend. Unfortunately overseas applicants are not eligible to apply.
Primary Supervisor: Professor Stephen B. Dunnett
Secondary Supervisor: Dr Simon P. Brooks
Project details:
Huntington’s disease (HD) is a genetic neurodegenerative disorder caused by a mutation in the gene that encodes the protein huntingtin. Functionally, it is characterised by the progressive worsening of cognitive, psychiatric and motor symptoms. Death occurs around 15 years after clinical diagnosis, and there is no effective treatment or cure. A neuropathological feature of the disease is the presence of inclusion bodies, small insoluble fragments of the huntingtin protein that aggregate within neuronal nuclei and glia. This aggregation process is believed to destabilise cellular homeostasis and induce cell toxicity via apoptotic mechanisms. The neuropathology is selective to the GABAergic medium spiny neurons of the striatum which induces dysfunction through the loss of integrity of the cortico-striatal circuitry. The evaluation of cognitive and psychiatric dysfunction is particularly important in HD as these symptoms appear early in the disease development and offer the initial opportunity for therapeutic intervention.
Mouse models of HD are used as model systems to study the neuropathology and functional deficits associated with the disease. These models share some of early cognitive and behavioural “psychiatric” symptoms but have not been fully characterised. Consequently, it is essential to develop better tests to probe the nature and severity of these cognitive and behavioural symptoms, and to determine the stage of early disease at which they first appear. The longitudinal characterisation process allows us to understand disease progression, to determine the suitability of specific models for specific therapeutic approaches, and to identify “phenoconversion” time points that are important when considering the timing of therapeutic trials.
Aims of the project
- Longitudinally characterise the development and severity of cognitive and behavioural dysfunction in HD mouse lines with established tests.
- Develop and validate novel tests to probe cognitive and behavioural function in mice.
- Assess the neuropathology underlying functional deficits using histological techniques.
Eligibility criteria:
The applicant must be eligible for UK/EU fee status and should hold a First or Upper Second Class Honours BSc degree and/or a Masters degree, or equivalent degree. If English is not the applicant's native language an English Language qualification, such as IELTS is required. For IELTS an average score of 6.5 is required with a minimum score of 6 in each element.
How to apply:
To apply, complete the online application form at: http://www.cf.ac.uk/regis/general/applyonline/index.html