Identifying circulating cell-free DNA epigenetic biomarkers for neurodegenerative disorders. PhD in Medical Studies (GW4 Biomed MRC DTP) Ref: 3643
About the award
Dr Emma Dempster, College of Medicine and Health, University of Exeter
There is currently no disease-modifying treatment for Alzheimer’s disease(AD), and current medications simply treat the symptoms of the disease. As AD can only be definitively diagnosed by autopsy, and neuropathology begins many years before clinical symptoms become manifest, there is considerable need for both diagnostic and prognostic biomarkers that can be used to distinguish AD cases early and predict the rate of cognitive decline and progression of pathology. Neuronal cell loss is a prominent pathological feature of AD and plays a key role in cognitive decline and begins early in AD pathogenesis. There is therefore huge potential in developing methods to detect signs of neuronal death early in the disease process to maximise any potential therapeutic intervention. Circulating cell-free DNA (cfDNA) consists of small double-stranded fragments of DNA that are found circulating in blood plasma or serum, and arises primarily from cell apoptosis.
There is considerable interest in using cfDNA as a non-invasive method (a ‘liquid biopsy’) for diagnosis and monitoring of disease. Epigenetic modifications are preserved in cfDNA and recent studies have shown that it is possible to exploit cell-type-specific patterns of epigenetic modification to identify the cellular origin of cfDNA present in the circulating blood plasma, including those of neuronal origin. To elucidate the specific epigenetic signature of distinct neural cell populations and to better understand the molecular aetiology of AD brain our group is currently profiling DNA methylation on purified populations of neuronal and non-neuronal nuclei isolated from post mortem brain tissue. This wealth of neural–cell type specific epigenetic data has enabled us to identify distinct neuronal epigenetic signatures that can be used to detect neural cfDNA fractions. This PhD project will use these neural cell-specific DNA modification signatures to develop assays that robustly detect and quantify cell-free neuronal DNA in circulating plasma. The student will then apply it to an extensive collection of clinical plasma samples collected from individuals with AD and mild cognitive impairment (MCI), comparing these to healthy controls. The approach can then be extended to other types of dementia, and tested in longitudinally-sampled cohorts to examine its utility as a diagnostic and prognostic biomarker. Specific aims are: 1) Design a panel of digital droplet PCR assays which can be used to accurately quantify levels of neuronal DNA in cfDNA samples. 2) Obtain plasma samples from individuals attending Dr Coulthard’s AD clinic in Bristol, quantify neuron-derived cfDNA in each sample and relate these values to clinical phenotype, established CSF biomarkers and outcome measures. 4) Profile cfDNA from a large well-phenotyped longitudinal AD collection of plasma samples obtained from the PROTECT study. 5) Determine the utility of this biomarker in individuals with MCI and other dementias to assess specificity.
This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£15,009 for 2019/20, updated each year) for 3.5 years.
For further information relating to the funding please see the main MRC GW4 BioMed website
This project is in competition with a number of other projects across the partnership; up to 18 studentships in total will be available.
Eligibility and Residency Requirements
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.
An EU student who has not been resident in the UK for at least 3 years prior to the start of the studentship is generally eligible for a fees-only award from the Research Council: to be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU; in the same way as UK students must be ordinarily resident in the UK.
For our regular recruiting round, the Doctoral Training Partnership has additional funding from the partner universities to support a limited number of EU students who do not meet the UK residency requirements, so long as they meet the criteria for a fees-only award: these studentship will therefore be fully funded (fees and stipend).
For full details on eligibility, please refer to the MRC GW4 BioMed website
Students with 'International' status are unfortunately not eligible to apply.
If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.
Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).
For further information regarding data protection for the Application Process and if you become a student on one of the Programmes please click here
For an overview of the MRC GW4 BioMed progamme, please see the website www.gw4biomed.ac.uk
In addition to those with traditional biomedical or psychology backgrounds, the DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences, and can fund additional training, including Masters to assist discipline conversion. Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.
If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.5 in any section) by the start of the programme.
How to apply
Applications Open on 29 September and close at 17:00 on Monday 25 November 2019
You will need to complete an application to the GW4 BioMed MRC DTP for an 'offer of funding'
Applying for an 'offer of funding'
Please complete the application form at https://www.gw4biomed.ac.uk/doctoral-students/ by 5pm Monday 25 November 2019.
The Research Theme Panels will complete the shortlisting and will aim to inform applicants by Thursday, 19 December 2019. If you are shortlisted you will need to:
- contact the lead supervisor of you chosen project in which you are interested, to arrange an informal interview (which can be in person, by telephone or by Skype) between 3 and 15 January 2020. Please note that interview expenses will not be available for candidates to attend these meetings.
- attend a formal interview, with a panel of four academics which will take place in Cardiff on 21 and 22 January 2020.
For further details of the application process please see the following web page www.gw4biomed.ac.uk/doctoral-students/
You do NOT need to apply to the University of Exeter at this stage - only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Exeter.
|Application deadline:||25th November 2019|
|Value:||Stipend matching UK Research Council National Minimum (£15,009 p.a. for 2019/20, updated each year) plus UK/EU tuition fees|
|Duration of award:||per year|
|Contact: PGR Recruitmentemail@example.com|