PhD Studentship – Role of the ribotoxic stress response in determining cell fate in human skin exposed to UV-light

Job title:

PhD Studentship – Role of the ribotoxic stress response in determining cell fate in human skin exposed to UV-light

Company

University of Cambridge

Job description

Applications are invited for a 3.5 year PhD studentship based within the MRC Toxicology Unit, University of Cambridge. The student will be working on a collaborative project jointly supervised by Anne E. Willis (MRC Toxicology Unit and Paul O’Mahoney (NIHR Health Protection Research Unit).Human skin provides a barrier against the external environment and is therefore exposed to a variety of environmental insults. When skin is exposed to ultraviolet (UV) radiation from sunlight, both acute and long-term local responses are stimulated including, inflammation, epidermal hyperplasia, carcinogenesis and keratinocyte cell death. Many of the harmful effects of UV-light on skin have been attributed to DNA damage and the activation of DNA damage signalling pathways. More recently, however, it has become clear that UV-induced RNA damage also plays a major role in the acute response of skin to UV radiation [1,2]. UV-induced lesions within RNA cause stalling of translating ribosomes, which leads to activation of the ribotoxic stress response (RSR) [2, 3]. To date, the RSR has been implicated in acute cell cycle arrest, the inflammatory response, epidermal thickening and keratinocyte cell death [1-3]. However, a more complete understanding of RSR’s role in the response of skin to UV, and the mechanisms through which this is achieved, remain to be determined.There is evidence that many proteins involved in post-transcriptional control of gene expression are phosphorylated in cells exposed to UV-light in an RSR-dependent manner, suggesting that the UV RSR targets post-transcriptional gene expression. Thus, the goals of this project are to determine how post-transcriptional gene expression is influenced by the RSR when skin is exposed to UV-light and what effect these mechanisms have on the fate of skin cells. Cell-wide proteomic techniques will be used to highlight novel post-transcriptional targets of the RSR. The influence of these target proteins on post-transcriptional control will be investigated using RNA sequencing technologies. Finally, the biological impact of these targets will be explored in human primary keratinocytes and human ex-vivo skin cell models.The overall aim of this project is to provide new insights into the molecular mechanisms and functional consequences of the response of skin to UV-light to help develop an informed approach to UV radiation risk management and health protection.Applicants should have or shortly expect to obtain a first or good upper second-class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject such as Biomedical Science. Strong analytical skills, in addition to creativity, curiosity, enthusiasm, and the ability to work in a team are essential.Full funding is provided by the NIHR Health Protection Research Unit in Radiation Threats and Hazards and the MRC Toxicology Unit. This includes Maintenance and the University Composition Fee (Home Fee rate only) with effect from 1 October 2025.This studentship is open to UK citizens or overseas students who meet the UK residency requirements (home fees) or who are able to augment the funds to cover the extra costs associated with international student fees. Full details of the University’s entrance requirements are specified here: .All formal applications will need to be made through the University Application Portal:If you have any queries regarding the application process, please contactFurther information can be found on our website:The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Expected salary

Location

Cambridge

Job date

Wed, 19 Feb 2025 23:10:42 GMT

To help us track our recruitment effort, please indicate in your email/cover letter where (globalvacancies.org) you saw this job posting.