Supervisors

Lead Supervisor: Professor Benjamin Housden, University of Exeter, Department of Clinical and Biomedical Sciences

CO-Supervisors:

Professor James Hodge, University of Bristol, Department of Physiology, Pharmacology and Neuroscience

Professor Krasimira Tsaneva-Atanasova,  University of Exeter, Department of Mathematics

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: Neuroscience & Mental Health

Project Summary: The aim of this project is to understand the mechanisms that cause motor neuron disease (MND) so that new treatments can be developed. This is important because MND is a devastating disease that results in death only three years after diagnosis. There are no cures and our understanding of why people develop the disease is limited. This project will use cutting edge techniques to investigate the mechanisms underlying MND, leading to effective therapies in the future. 

Project Description: The aim of this project is to investigate the cellular mechanisms underlying motor neurone disease (MND) to facilitate the development of new therapies in the future. This is important because MND has a short life expectancy (3 years from diagnosis), the impact on quality of life is severe and there are currently no effective treatments. There is a clear need to gain a better understanding of the disease to inform the development of effective therapies.

Our approach to uncovering mechanisms of MND is to use genetic interaction analysis to gain insight into the genes and pathways that are involved in loss of viability in MND cells. We have developed Drosophila cell culture models expressing mutant version of human proteins known to be associated with MND (SOD1, FUS and TDP43) and have demonstrated that these models share characteristics with human models of the disease (e.g. alterations in cell viability and protein localisation). Using these new models, we have screened for genetic interactions between two mutant forms of TDP43 and approximately 350 kinases. This has resulted in the identification of several candidate genetic interactions that are now being validated. In addition, we have profiled transcriptional changes that occur when mutant forms of TDP43 are expressed. These datasets provide a powerful basis for mechanistic analysis.

A major problem in determining mechanisms of human disease is that knowledge and candidate therapies identified in cell culture systems are not always relevant in patients. We have developed methods to overcome this issue by cross comparing between cell models derived from distant genetic backgrounds. Specifically, by comparing Drosophila cells to human cells modelling the same disease, it is possible to distinguish mechanisms and drug targets that are relevant across diverse systems from those that are specific to one system. This results in mechanistic understanding and candidate drug targets with a high chance of relevance in the clinic. In this project, the student will compare results between Drosophila cells, Drosophila in vivo models and human iPSC models of MND to gain new knowledge of the underlying mechanisms that are likely to be relevant to patients.

Initially, the student will build on our previous work by extending the genetic interaction screens to cover 150 additional genes for which clinically approved chemical inhibitors already exist (Objective 1). By focusing on this gene set, identified genes and pathways have a high chance of rapid translation towards new therapies. Using these data combined with the previous screen results and the transcriptomic data, the student will then use computational approaches to map pathways associated with MND (Objective 2). Finally, the student will investigate the identified pathways using two diverse models of MND. The first is an in vivo Drosophila model and the second is an iPSC model. By investigating these new pathways in Drosophila cells, in vivo and using human cell models, we can apply a filter to remove MND-linked mechanisms that are specific to a single model system and focus on those pathways that are common between diverse genetic environments. This greatly increases the chances that our results will be relevant to human patients.

Objective 1: To map genetic interactions with 150 potential drug targets.

Objective 2: To map biological pathways involved in MND using computation methods

During this objective, the student will guide the data analysis approach and choosing the most appropriate method for the task. For example weighted gene co-expression network analysis (WCNA), similarity network fusion (SFN) and/or topological data analysis (TDA), with guidance from Professor Krasimira Tsaneva-Atanasova.

Objective 3: To validate novel MND pathways using human iPSC and Drosophila in vivo models

The student will decide which genes and pathways to pursue based on advice from the supervisors and their own literature-based analysis of the candidates. These decisions will be guided with input from Prof. James Hodge, who has extensive experience in characterisation of fly models of neurodegenerations.

Overall, we expect this project to address an important biological question, which will lead to significant impact on human health in the future. The project will also provide the student with a broad range of skills that will be invaluable in many different future careers.

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