Supervisors

Lead Supervisor:

Professor Albert Basson, University of Exeter, Department of Clinical and Biomedical Sciences

Co-Supervisor:

Professor Anthony Isles, University of Cardiff, Department of Psychological Medicine and Clinical Neurosciences

Dr Clemence Bernard, University of Exeter, Department of Clinical and Biomedical Sciences

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

Summary:

The Kdm5b gene is linked to a number of neurodevelopmental disorders, including ADHD, autism, bipolar disorder and intellectual disability. Using a unique mouse model, we recently identified a neurobiological mechanism that underlies socio-communicative deficits in this model and showed that targeting this mechanism can restore normal function. The aim of this project is to use cutting-edge approaches to identify the brain regions and cell types that control these behaviours, study the brain circuits affected by Kdm5b deficiency and understand how treatments can restore normal function. This research will have important implications for understanding socio-communicative deficits in neurodevelopmental disorders.

Main Description:

Background Mutations in genes encoding chromatin modifying and interacting proteins are frequent causes of neurodevelopmental disorders. Using a mouse model, we have been studying one of these, Kdm5b, which encodes a protein that regulates gene expression by modifying the structure of chromatin in the cell nucleus. Loss of function variants in this gene are associated with intellectual disability and autism spectrum disorders. Kdm5b-deficient pups exhibited striking socio-communicative deficits.

By studying changes in gene expression, we have identified abnormal expression of a gene encoding an important neurotransmitter receptor in the developing brain and found that treatment of mice with a pharmacological compound that target this receptor can rescue the vocalisation deficits.

These findings create an exciting opportunity to identify the brain regions, brain circuits and molecular mechanisms that control socio-communicative behaviours that are often abnormal in neurodevelopmental disorders.

Research question

We now need to find answers for a number of fundamental questions:

1) What brain regions and cell types control vocalisations in young mice and how does Kdm5b deficiency affect the activity of these cells and brain areas during behaviour?

2) How does treatment with pharmacological compounds restore normal brain function and behaviour?

3) How do these abnormal brain functions impact other behaviours during early postnatal development?

Specific objectives are:

1. To identify the key brain regions activated during vocalisation behaviours and affected by Kdm5b deficiency,

2. To use state-of-the-art single cell sequencing, immunostaining and conditional gene deletion approaches to identify the cell types affected by Kdm5b deficiency,

3. To use a combination of imaging, molecular and electrophysiological assays to determine how treatments that can restore normal behaviour work 

4. To develop and use new approaches to assess if Kdm5b deficiency affect other relevant behaviours during early postnatal stages.

During year 1 and 2, the student will use reporters of neuronal activation to identify the brain regions and cell types activated during vocalising behaviours, identify those that are affected by Kdm5b activity and rescued by pharmacological treatment.

During year 2 and 3, the student will use electrophysiological approaches to further characterise and identify abnormal brain circuits in Kdm5b mutants.

During year 3, the student will work closely with the Isles laboratory and experts in the GW4 BioMed2 partner organisation the Mary Lyon Centre as part of the MRC National Mouse Genetics Network to determine how altered brain activity impact behavioural development. The student will gain expertise in a range of cutting-edge in vivo and data science skills, including the first stages of translational research with pre-clinical models and a proficiency in data handling that are highly desirable and transferable to many careers.

The student will take ownership of experimental design from the start (see below). Once the core objectives outlined above have been met, the student will have the opportunity to shape the remaining time of their PhD by pursuing areas of research that suit their interests. For instance, they may perform neurophysiology, behavioural studies, or cutting-edge chromatin and next generation sequencing experiments.

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