Integrative analysis of whole genomes and transcriptomes from multiple cell types in rare disease patients. MRC GW4 BioMed DTP PhD studentship 2025/26 Entry, Department of Clinical and Biomedical Sciences Ref: 5238

Supervisors

Lead Supervisor: Dr Mattia Frontini, Univeristy of Exeter

Co-Supervisor: Dr Sarah Westbury, University of Bristol

The GW4 BioMed2 MRC DTP is offering up to 21 funded studentships across a range of biomedical disciplines, with a start date of October 2025.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 58 students over 3 cohorts in its second phase.

The 120 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair

• Neuroscience and Mental Health

• Population Health Sciences

 

Applications open on 10th September 2024 and close at 5.00pm on 4th November 2024.

Studentships will be 4 years full time.  Part time study is also available.

Project Information

Research Theme: Population Health Sciences

Summary: Comprehensive genetic analysis using whole genome sequencing (WGS) still fails to identify the genetic cause of diseases in about 50% of patients with rare diseases. To increase this yield, the NIHR BioResource for Rare Disorders launched the RNA phenotyping initiative, which combines RNA-sequencing and proteomic data with WGS for 1000 patients with rare diseases. This PhD project will develop new approaches to integrate these data to identify new causes of diseas

Project Description: The use of Whole-Genome Sequencing has dramatically increased the diagnostic yield and shortened the time to diagnosis for individuals affected by rare diseases. However, WGS still fails to identify the underlying genetic cause in about 50% of patients.
This is due to several factors, mainly:
(i) lack of statistical power due to small sets of cases with different genetic aetiology,
(ii) difficulty in predicting the consequences of a number of causal genetic variants, and lastly,
(iii) challenges with identifying structural variants using current WGS techniques.

To increase the percentage of individuals receiving a diagnosis the NIHR National BioResource for Rare Diseases launched the RNA phenotyping initiative. Here, WGS is supplemented with RNA-sequencing from four highly purified blood cell types and proteomic data from the same cells and plasma.
This unique dataset provides an exciting opportunity to complement genome analysis with functional measurements of gene expression at the messenger RNA and protein level. Understanding how gene expression varies with genotype and disease status will allow the identification of novel genetic aetiologies for rare disorders. It will enhance our understanding of human biology, improve the diagnostic yield of clinical genetic analyses, improve prognostication, and inform the development of treatments.
The candidate will join a group with an extensive track record of studying blood disorders and they will be part of a multi-disciplinary collaborative research environment that includes clinicians, biologists, statisticians and bioinformaticians. The aim of the project is to develop approaches for integrating and exploiting the novel collected data and apply these to discover new causes of disease in a unique cohort of one thousand rare disease patients, boosting the diagnostic power of genetic testing and broadening access to precision medicine.
The candidate will take ownership of identifying relevant computational methods, applying them and subsequently developing new methodology where necessary, to integrate genotype and gene expression data. To focus the studentship, the candidate will work with data from a selected group of patients enrolled with bleeding secondary to a platelet function disorder and unresolved genetic cause. In addition to the initial sequencing and proteomic data, the student will have access to laboratory data generated using recall by genotype studies. Employing this, they will lead the analyses and with the direction of the supervisory team, will coordinate the assembly of evidence to support the publication of their findings in peer-reviewed journals.
Focusing on blood disorders in general, and platelet function disorders in particular, will enable to student to make the most from the specialist knowledge of the project supervisors in this area. However, the methodologies developed will be relevant to a broad range of disease areas. Furthermore, many genes implicated in platelet function are also implicated in the development and function of other cell types, such as neurons, immune cells hepatocytes and melanocytes. Depending on the student’s interests and the loci investigated, it will be possible to investigate broader non haematological phenotypes within the study cohort

Funding

This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£19,237 p.a. for 2024/25, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

Eligibility

Residency:

The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.  All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria:

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences.  Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:

If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. Please refer to the details in the following web page for further information https://www.exeter.ac.uk/study/englishlanguagerequirements/

Data Protection

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”).

Further Information

For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk

Entry requirements

Academic Requirements

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English Language Requirements

If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. Please refer to the relevant university website for further information.  This will be at least 6.5 in IELTS or an acceptable equivalent.  Please refer to the English Language requirements web page for further information.

How to apply

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk.  You may apply for up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’.  If successful, you will also need to make an application for an 'offer to study' to your chosen institution.

Please complete the online application form linked from our website by 5.00pm on Monday, 4th November 2024.  If you are shortlisted for interview, you will be notified from Friday, 20th December 2024.  Interviews will be held virtually on 23rd and 24th January 2025.

Further Information

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on our website.

Summary