EASTBIO: Cell type specific proteomics in longevity and ageing using Genetic Code Expansion technology

Aim 1, focuses on labelling proteomes in selected cell types using clickable non-canonical amino acids (ncAAs). We will generate transgenic C. elegans expressing genetic code expansion machinery components, namely an engineered pyrrolysyl-tRNA-synthetase/tRNA pair that recognises the clickable ncAA, enabling stochastic proteome-wide incorporation of the ncAAs.

Critically, only proteins from cells expressing the synthetase/tRNA pair are labelled. Temporal control is achieved by adding the ncAA at desired times. Labelled proteins will be extracted via biotin attachment through click reactions, followed by purification with streptavidin beads.

This method, unlike the existing alternative (BONCAT), avoids reliance on specialized bacterial diets to deliver the ncAA. Aim 1 will be carried out in collaboration with Dr. Greiss, who has optimized genetic code expansion for C. elegans (PMID:34350826,24727715).

Aim 2, will apply this technology to resolve tissue specific proteomes, including post-translational modifications, and newly synthesised proteins across early adulthood and ageing. Proteomes will be harvested under different conditions, such as long/short-lived mutants and pro-longevity interventions (e.g., B. subtilis diet, PMID:31940482). Proteome analysis will be carried out at the Centre for Hidden Cell Biology (UoE). Prioritised tissues will be nervous system, muscle and intestine, alongside global proteomics for comparison.

The expected outcomes of Aims 1and 2 include a) the development of an optimised spatio-temporal proteomics technology thus far not established in C. elegans b) the generation of spatio-temporally resolved proteomes of longevity, which will be made available as a scientific resource.

In Aim 3, we will perform comparative analysis of the generated proteomes to identify: a) Gene expression or post-translational modifications linked to lifespan extension.

b) Global and tissue-specific ageing signatures.

We will validate the most prominent hits via mutant analysis and tissue specific knockdown/overexpression analysis, using assays for lifespan and healthy ageing.

This project advances our understanding of ageing at organismal and tissue-specific levels while establishing versatile proteomic tools for broader research applications.

Central to the PhD project is training in Bioinformatics for proteomics data analysis, state-of-the-art molecular genetics, biochemistry and behavioural analysis methods. The project is cross-disciplinary developing state-of-the-art synthetic biology methods for the study of longevity and healthy ageing.

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP). Detailed guidance on the application process, and the EASTBIO Application and Reference Forms can be found at How to Apply | Biology.

Please send your completed EASTBIO Application Form along with a copy of your academic transcripts (as a pdf) to INCR.PostgraduateRecruitment@ed.ac.uk. You should also contact your referees and ask them to submit their references (on the EASTBIO reference form template) to INCR.PostgraduateRecruitment@ed.ac.uk by the application deadline of 16th November 2026.

Funding Notes

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees. The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees. There is a cap on the number of international students the DTP recruits. It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our University.

Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.