PhD Studentship : Using Single Cell Approaches to Unravel the Mechanistic Basis of Long Term Epigenetic Memory (CASE), BBSRC SWBio DTP PhD Studentship 2025 Entry

About:

The BBSRC-funded SWBio DTP involves a partnership of world-renown universities, research institutes and industry, based mainly across the South West and Wales.

This partnership has established international, national and regional scientific networks, and widely recognised research excellence and facilities.

We aim to provide you with outstanding interdisciplinary bioscience research training, underpinned by transformative technologies.

Project Description

In recent years evidence from multiple disciplines and model organisms has revealed that exposures to stress during early life can lead to altered health and susceptibility to stressors later in life. While many of the best known examples report on maladaptive changes, in many cases, including in experiments from our own laboratory, exposure of fish to stressors during the epigenetic reprogramming period resulted in increased tolerance upon re-exposure to the same stressor. While it is generally accepted that these effects are mediated, at least in part, by long lasting changes in the epigenome, the precise mechanisms by which they occur are unknown. Uncovering the mechanisms accounting for increased tolerance to stress is of critical importance and applicable to a range of fields within the biosciences, from prevention and management of disease in humans, to increased welfare and productivity in farmed animals and to better understanding and management of the threats affecting biodiversity.

This project will test the following hypothesis:

1 - During the period of epigenetic reprogramming the epigenome is more susceptible to stressor-driven alterations which will persist over the life time of individuals

2 – When changes in the environment act at the cellular level via activation of transcription factors, changes in the epigenome occur in the genomic regions of transcription factor binding sites and lead to greater responsiveness to the same stimuli later in life

The project will utilise a fish model with well characterised developmental reprogramming that follows a similar pattern to humans and other vertebrates (the medaka), making the data generated applicable across vertebrate species. A combination of phenotypic analysis, single cell transcriptomics and epigenomics, Chip-Seq and advanced bioinformatics will be employed to document the precise molecular events underpinning reprogramming across all individual cell types, how exposure to stressors linked with transcription factor activity (i.e, metals, oestrogens and temperature) modulate the epigenome and whether these changes are long lasting and condition the response of individuals to those stressors later in life.

The student will receive extensive training in state-of-the-art techniques including, in vivo experimental techniques, transcriptome and epigenome sequencing at the single cell resolution and advanced bioinformatics analysis.

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