PhD Studentship: Developmental consequences of heat stress during early mammalian embryogenesis

View All Vacancies
Science
Location:  UK Other
Closing Date:  Friday 10 May 2024
Reference:  SCI271

Supervisor: Kevin Sinclair

Secondary Supervisor: Ramiro Alberio, David Gardner

Subject Area: Environment and developmental biology

Epidemiological evidence in humans indicates that acute heat exposure around the time of mating results in pregnancy loss, with potential long-term consequences for offspring health and wellbeing; although these latter adverse effects are poorly understood. Similar effects of acute heat stress on embryo survival and development are seen in other species. Identifying underpinning mechanisms requires the use of appropriate animal models. Farm animal and human embryos share many aspects of early development including gene regulatory networks, developmental timing, and signalling requirements for cell-lineage establishment. Thus, in addition to being species of clinical importance in their own right, these animals represent excellent models for the study of human embryogenesis.
This PhD will test the hypothesis that an acute period of heat stress around the time of mating epigenetically alters embryo development in a manner that can compromise pregnancy establishment and the health and wellbeing of offspring derived from surviving embryos. This proposal will undertake detailed morphokinetic, histological, metabolic and molecular analyses of bovine and porcine embryos up to and including gastrulation. In so doing, it will complement in vivo assessments of porcine embryo development (extending to F2 embryos) and measurements of cardiometabolic health in offspring (F1), which will be undertaken in parallel by other members of the team.
Specifically, this PhD will address the following two objectives:
(1) Establish morphokinetic, metabolic and epigenetic effects of acute heat stress in cattle and pig pre-hatching (elongation) embryos.
(2) Establish consequences of such effects on cell fate in gastruloids formed from stem cells derived from control or heat-stressed pig blastocysts.
A range of temperatures (representing extremes of core-body temperature) will be assessed during in vitro embryo culture. State-of-the-art techniques include morphokinetic assessments undertaken using time-lapse microscopy complemented by immunohistological quantification of cell-lineage fate. Metabolic responses will be established by extra-cellular flux analyses of mitochondrial function.
The study will then characterize (lineage markers, karyotype) and sex stem-cell lines from Control and Hyperthermic treated embryos using established in-house protocols. Epigenetic status will be determined which will provide some insight into potential long-term developmental consequences of short-term heat stress during the study period. Finally, these lines will undergo induced gastruloid formation and molecular characterization for lineage mapping.

Award Start Date: 01/07/2024

Duration of Award: 36 months

This research studentship is only available to UK citizens and includes payment of tuition fees and a tax-free stipend based on BBSRC rates (currently £19,237 per year).

Minimum qualification BSc (Hons) in a biological or closely related discipline - 2:1 or above

How to Apply

Candidates are welcome to contact Prof. Kevin Sinclair [email protected] with any queries and for an informal discussion.
Applications, comprising a covering letter detailing why you want to study a PhD on this subject area together with a detailed CV (including the names and addresses of two referees), should be sent to [email protected]

Please title the email subject ‘Prof. Kevin Sinclair advertised Nottingham PhD studentship’

Closing Date: 10/05/2024