Mechanisms of alternative splicing in neurodegeneration and ageing

After decades of research, we still have limited mechanistic understanding of the two most studied anti-ageing therapies, reduced mTor signalling (e.g. rapamycin) and dietary restriction (DR). Both these mechanisms are thought to operate by integrating environmental information to then exert pro-longevity physiology. In the fly (Drosophila melanogaster), both DR and reduced mTor signalling (Simons lab) instantly rejuvenate (within days).

Recently Simons (main supervisor) has discovered both these effects are associated with alternative RNA splicing. These findings fit with the increasing appreciation of alternative splicing in disease and ageing, providing a targetable gateway to instigate a rejuvenated physiological state. One of the most debilitating age-related diseases is neurodegenerative disease in which differences in splicing are also strongly implicated.

The aim of this PhD project is to use the data already available in the hosting lab on splicing during ageing, DR and mTOR suppression, to now modulate these mechanisms and measure effects on lifespan and on neuronal functioning. You will test these mechanisms using the latest techniques in fruit fly functional genetics measuring both lifespan and learning and memory. You will both manipulate the spliceosome components, the protein complex that regulates splicing as well as individual genes and isoforms. Furthermore, you will aim to extend these results to neurodegeneration using a well-established genetic model.

You will be integrated in two vibrant research groups in the School of Biosiences at Sheffield hosting leading biologists. We look for a student that is passionate about science, has a quantitative mindset and enjoys experimental biology.

For informal enquiries about the project, please contact Dr Mirre Simons [email protected].

About YBDTP:

YBDTP brings together world-class bioscience research and innovation, as well as excellence in doctoral supervision, across the region. YBDTP will fund postgraduate researchers at the Universities of Leeds, Sheffield, York, Bradford, Hull, Leeds Beckett, Sheffield Hallam and Teesside forming a strong regional training partnership. In YBDTP you’ll benefit from a regional doctoral training programme that has interdisciplinary collaboration at its core. The aim is to enable you to develop a range of research skills in biological, biotechnology and biochemical areas as well as equip you with core data analysis and professional skills that are necessary for bioscience research and related non-academic careers.

https://www.whiterose-mechanisticbiology-dtp.ac.uk/yorkshire-bioscience-dtp/

Funding Notes:

Funding: A tax-free annual stipend at the standard UKRI rate (£19,237 for 2024/25 entry), research costs and tuition fees at UK rate

Academic year: 2025/26

Open to: International (including EU) and UK (home) students

Eligibility:

Open to International (including EU) and UK (home) students.

You can apply if you have, or are expecting to gain, at least an upper second-class honours degree or equivalent. Due to the interdisciplinary nature of this programme, we welcome applications if your background is in any biological, chemical or physical science or mathematics and are interested in using your skills in addressing biological questions. International students should check if they meet the entry requirements for their country.

We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international (EU and non-EU) applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. 

The Yorkshire Bioscience DTP is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Not all projects will be funded; a limited number of candidates will be appointed via a competitive process.

English language:

If English isn’t your first language, you may need to provide evidence of your English language ability.

How to apply:

Application deadline: 5pm, Friday 14^th March 2025

To submit your application, click on the link to the Expression of Interest form in the Funding Notes section of any of your chosen projects. You can apply for up to 3 YBDTP projects (which can be at different universities).

We would advise you to read the questions in the form before submitting your application. Inside the form there is a link to a document for you to see the questions in advance.

If you have any questions about the application process, please email [email protected].

If you have any questions about the project you are interested in, please email the project supervisor (details inside the project description).

How we allocate:

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. If you’re shortlisted, you’ll be invited for an interview on a date to be confirmed in February 2025. You’ll be notified as soon as possible after the interview dates whether your application has been successful, placed on a reserve list or unsuccessful. If you are successful, you’ll be required to confirm your intention to accept the studentship within 10 days.

Terms and conditions:

The studentships are fully funded for four years, and you must complete your PhD in four years.

You’ll receive the UKRI minimum doctoral stipend per year for your living costs, which is paid to you in regular instalments. The UK Research and Innovation (UKRI) stipend is tax free and does not need to be paid back.

International students will need to have sufficient funds to cover the costs of their student visa, NHS health surcharge, travel insurance and travel to the UK as these are excluded from UKRI funding.