The methylation of proteins is a key post-translational modification used for fine-tuning vital cellular processes. In recent years, it has become apparent that proper regulation of protein methylation is vital for the correct formation of sub-cellular structures, including nuclear Cajal bodies and gems. In turn these structures, which are proposed to be formed by the process of liquid-liquid phase separation, are vital for the regulation of gene expression and messenger RNA processing. A number of RNA binding proteins, including SMN, FUS and TDP-43, found in phase-separated structures are vital for the functioning of motor neurones, as demonstrated by their involvement in the motor neurone diseases Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis.
Using motor neurones differentiated from human induced pluripotent stem cells, we have recently discovered that inhibition of protein methylation can lead to defects in motor neurons, which mimic some those seen in motor neurone diseases, including alteration to sub-cellular phase-separated structures and functional defects measured using single cell electrophysiology. Following on from these recent findings, this interdisciplinary project will combine fundamental cell biology (Sleeman group) with applied neuroscience (Miles group) to investigate the roles of protein methylation in the healthy differentiation and function of motor neurons. Techniques used will include cell culture, enhanced resolution fixed and live cell microscopy, whole-cell patch-clamp electrophysiology and quantitative (SWATH and SILAC) proteomics.
HOW TO APPLY
Application instructions can be found on the EASTBIO website- http://www.eastscotbiodtp.ac.uk/how-apply-0
1) Download and complete the Equality, Diversity and Inclusion survey.
2) Download and complete the EASTBIO Application Form.
3) Submit an application to St Andrews University through the Online Application Portal
Your online application must include the following documents:
- Completed EASTBIO application form
- 2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)
- Academic Qualifications
- English Language Qualification (if applicable)
Unfortunately due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by Monday 5th December 2022.
Queries on the project can be directed to the project supervisor.
Queries on the application process can be directed to Jess Fitzgerald at [Email Address Removed]
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