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HNRNPD: a master regulator of microRNAs in response to ischemic stress?

University of Exeter - Exeter Medical School

Qualification Type: PhD
Location: Exeter
Funding for: UK Students, EU Students
Funding amount: BBSRC SWBio DTP funded CASE studentship available for September 2022 entry. The studentship will provide funding of fees and a stipend which is currently £15,609 per annum for 2022-23, on a full time basis
Hours: Full Time
Placed On: 22nd October 2021
Closes: 6th December 2021
Reference: 4271

The human body consists of many different types of cells. It has long been recognised that cell type is flexible, and that cells may change into different types of cells in response to several factors, one of which is exposure to stresses such as high glucose or oxygen starvation. 

Cell identity changes in response to cell stress underpins a lot of common chronic diseases such as cancer, diabetes and kidney disease. The factors that lead a cell to become (or remain) a particular cell type are still being unravelled, but we know that both genes that code for proteins, and those that represent the ‘dark matter’ of the genome are involved. It is now becoming evident that these ‘dark matter’ genes, which produce products known as non-coding RNAs may be particularly important in determination of cell identity, since this class of genes is very responsive to the environment in which a cell finds itself. 

In past work, we have discovered a gene (named HNRNPD) that controls many non-coding genes, but especially one class of non-coding genes called microRNAs, which has a pivotal role in cell identity decisions. In this project we plan to identify and characterise miRNAs that are regulated by HNRNPD but also involved in cell identity decisions, and demonstrate that by altering their levels we can protect cells from changing identity in response to oxygen starvation. These could be targeted in the future to protect kidney cells from oxygen starvation during major surgery, multiple organ failure or sepsis, which is sometimes called blood poisoning. 

We will first uncover which of the >2000 miRNAs known to exist is responsive to temporary oxygen starvation in rat kidneys from which data are already available. Secondly, we will use human kidney cells where we have removed HNRNPD to identify which miRNAs are regulated by HNRNPD. From these data, we will then identify miRNAs that are both regulated by HNRNPD, and by temporary oxygen starvation. We will then use a statistical process to identify which of the resulting miRNAs are likely to be the most important, and then turn them on or off as necessary in human kidney cells in culture to investigate the effects of this on cell identity. 

This work may identify some miRNAs that could be used in the future to protect kidney cells from changing identity following major surgery or other causes of interrupted oxygen supply to the body’s tissues. 

Eligibility 

To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria. 

A fully-funded four year SWBio DTP studentship will cover 

  • a stipend* at the standard Research Council UK rate; currently £15,609 per annum for 2022-23
    •    research and training costs 
    •    tuition fees (at the standard Research Councils UK rate) 
    •    additional funds to support fieldwork, conferences and a 3-month internship 

Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship.  Any further queries in relation to residency must be directed to the institution. 

* An enhanced stipend is available for students with a recognised veterinary degree qualification (£24,090 per annum for 2022-2023). There may also be enhanced stipends associated with projects that have a CASE partner (highlighted as *CASE in the project lists). 

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