Identifying therapies to enhance muscle stem cell function in ageing using advanced imaging and AI models

Project details

First supervisor: Dr Robert Knight

Second supervisor: Dr Mads Bergholt

Funding available: Self-funded PhD students only. We welcome applicants who are interested in applying for personal funding to work on the project.

Tuition fees: to be paid by student.

Bench fees £5,000 per year: to be paid by student.

Mode of study: Full-time

Eligibility: Home/EU/Overseas

Start date: Until a suitable candidate is found

Application deadline: Until a suitable candidate is found

Reference number: 2024/10/RK/DOCS

Project description

Muscle function is essential for healthy ageing, yet we know deficits in muscle stem cell (muSC) function occur when we get older, resulting in weakness and frailty. Increasingly, ageing research is looking to find novel and effective interventions to enhance muSC function in vivo and so promote a better regenerative response to injury and impaired muscle function. The challenge is how to identify such factors in the complex environment of the muscle, in which many cell types are important for controlling muSC function. By understanding how different cells communicate in regenerating muscle and how these affect the ability of the muSC to migrate to damaged muscle and effectively replace damaged myofibres forms the basis for this project.

We have investigated how muSCs are regulated by in vivo imaging in zebrafish and mouse to show they respond to mechanical force and can adapt their behaviour to respond to injury. We have profiled muscle from a zebrafish genetic model of accelerated ageing caused by loss of telomerase function and shown this recapitulates many of the key features seen in human ageing. The project therefore aims to test the function and importance of a set of molecules we have identified that we predict may be important for controlling muSC behaviour by CRISPR/Cas9 knockout and gene over-expression. To understand how muSC function corresponds to the molecular composition of the tissue the student will perform molecular profiling using Raman imaging and DESI mass spectrometry. Outcomes will reveal molecules controlling muSC function in ageing and how muSC behaviour is affected by the molecular profile of the tissue.

Person specification

• Master's or equivalent research experience in biology including background in molecular genetics (essential)
• Experience of performing advanced imaging (desirable)
• Experience of working with zebrafish (desirable)  

Research training

Students will learn about ageing biology, particularly of muscle, and therapeutic interventions proposed to improve health in ageing. They will learn the following specific techniques:

• Molecular biology
• Gene manipulation and transgenesis in zebrafish
• Advanced imaging methods (spinning disc confocal, Raman imaging, DESI-MS)
• Use of AI models to interpret imaging data (time-lapse and complex spectral data)

Additionally they will gain skills in presenting to their peers, learn how to form complex hypotheses and plan and deliver experiments in a supportive and collegial atmosphere.

Next steps

Applicants are strongly encouraged to discuss the project with the first supervisor prior to submitting an application. 

Please apply online at apply.kcl.ac.uk following these steps:

1. Register a new account/login
2. Once logged in, select Create a new application
3. Enter ‘Dental and Health Sciences Research MPhil/PhD (Full-time)' under Choose a programme. Please ensure you select the correct mode of study
4. Select start date
5. Please note: Applicants must include the project reference number (2024/10/RK/DOCS) in the 'Research proposal' and 'Funding (point 5)' sections of the application.

Contact for further information

Dr Robert Knight

robert.knight@kcl.ac.uk

Related Centre: Centre for Craniofacial & Regenerative Biology

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