Supervisors: Dr Shipra Bhatia; Prof F Mueller
Application deadline: 16 November 2026
Funding: Funded PhD Project (Students Worldwide)
About the Project
The vertebrate body contains hundreds of specialised cell types, produced by tightly controlled activation of genes in specific places and times during development. This control depends on enhancers—noncoding DNA elements that recruit transcription factors to switch genes on in the right cellular contexts. Scattered across long stretches of the “dark genome,” to form large regulatory landscapes, their conserved arrangement in position, order and orientation across vertebrate evolution suggests underlying organisational principles that remain largely unknown. Until these rules are defined, we cannot fully explain how gene expression variation drives evolutionary change or predict how disease associated mutations disrupt regulatory architecture.
A key step toward this understanding is mapping the precise cell‑ and tissue‑specific activities of enhancers in vivo. Dr. Shipra Bhatia’s research at the Institute of Genetics and Cancer addresses this challenge by developing zebrafish models that enable real‑time visualisation and functional testing of enhancer activity. Using the PAX6 locus—an exemplar of enhancer‑mediated regulation and a master controller of eye development (Bhatia et al., 2021; Uttley et al., 2023)—the team has established methods to synthesise large genomic regions de novo, deliver them into zebrafish, and assay synthetic regulatory landscapes during embryogenesis. Combining single‑cell omics with high‑resolution live imaging, they have uncovered previously unrecognised layers of regulatory logic within the PAX6 domain.
Project Aim
Functional delineation of cell type specific enhancer activities within the PAX6 regulatory domain
Phase 1: Hypothesis Development (Months 0–6)
Single cell datasets (RNA seq and ATAC seq) generated by the host laboratory across multiple stages of zebrafish development, will be analysed to identify enhancers or enhancer clusters active in PAX6 expressing eye and brain cell types. This analysis will lead to developing a hypothesis describing spatial and temporal enhancer dynamics at both synthetic and endogenous PAX6 loci.
Phase 2: Resource Generation (Months 3–18)
CRISPR–Cas9 engineering will be used to modify synthetic regulatory landscapes in existing transgenic zebrafish lines, generating targeted deletions of individual enhancers or enhancer groups.
Phase 3: Data Generation and Analysis (Months 18–36)
Embryos carrying engineered deletions will be analysed using confocal and lattice light sheet microscopy, alongside single cell technologies (CAGE and ATAC seq), to determine how perturbations alter enhancer activity and gene expression outputs.
Training environment
This PhD project will provide interdisciplinary training in synthetic biology, single cell omics, advanced imaging, and computational analysis. It aligns closely with ongoing work in the host laboratory on BBSRC funded consortium Decoding the Genome’s Hidden Grammar, ensuring extensive mentoring, training, and networking opportunities.
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 [contact details available in the full listing]. You should also contact your referees and ask them to submit their references (on the EASTBIO reference form template) to [contact details available in the full listing] 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.
