Understanding the contribution of SHANK3 LLPS in autism and cancer

About the Project

In this exciting research project, you will investigate SHANK3, a key protein that facilitates communication and adaptation in brain cells. SHANK3 acts as a molecular 'organiser', bringing together receptors, signalling molecules and the cell's internal skeleton to promote healthy brain development and learning. If SHANK3 does not function properly, the consequences can be severe. Genetic changes in SHANK3 are one of the most common single-gene causes of autism spectrum disorder (ASD). Emerging research also suggests that this same protein may influence pathways related to cancer, including K-Ras and Wnt signalling. This project will explore how these seemingly different diseases may share common molecular mechanisms.

The student will:

• Gain hands-on experience with cutting-edge tools such as cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) to visualise proteins in great detail.
• Discover how SHANK3 organises receptors and shapes the cell’s internal framework (the actin cytoskeleton), thereby influencing learning, memory and cell growth in our neuronal models.
• Investigate disease-causing mutations. Explore how genetic mutations alter protein structure, disrupt cellular organisation and contribute to neurodevelopmental disorders and cancer.
• Work with human stem cell-derived neurons. Assess how structural changes translate into functional consequences in human neuronal models.

This interdisciplinary project sits at the intersection of neuroscience, structural biology, cell biology and cancer research. The successful applicant will benefit from a structured teaching environment at the Manchester Cell Matrix Centre, in collaboration with the University of Liverpool, where we have our own in-house cryo-electron microscope, NMR spectrometer, and stem cell facilities. Enquiries are welcome.

Eligibility

Candidates are expected to hold a minimum upper second class honours degree (or equivalent) in a related area / subject

Before you Apply

Applicants mustmake direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Cell Matrix Research Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester)

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website View Website