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Click here to search FindAPhD.com for PhD studentship opportunities(BBSRC DTP) Delineating the gene expression timeline of a mitochondrial stress response regulating ageing
About the Project
The genome is the blueprint of any living systems. However, it is the regulation of gene expression that enables life. For transcription to take place, the molecular machinery involved must access genomic DNA. In eukaryotes, every 150 base pairs of DNA is wrapped around an octamer of core histones forming the nucleosome, the fundamental unit of chromatin. These core histones are heavily modified and it is thought that the modifications form a code that regulates access to DNA. Methylation of histone 3 lysine 4 (H3K4) is an important component of this code and is strongly associated with accessible and transcribed DNA. However, once a transcript is produced, it needs to be translated to produce a protein. It is known that regulating translation is crucial for many stress responses. On one hand, a translational block is required to conserve energy and reduce protein aggregation but, on the other hand, specific translation is enabled to produce protective proteins such as chaperones and proteases. Thus, specific stress-induced transcripts are differentially regulated compared to normally produced mRNAs. This project will focus on a well-characterised mitochondrial stress response that has so far been characterised as essentially transcriptional. Indeed, we have shown that H3K4 methylation is required to activate this response. However, the timeline of the molecular events underpinning the response remains unknown. Based on our new data, we hypothesise that the early events of the mitochondrial stress response are likely to affect translation. We propose a model whereby there is an initial alteration in translational programming followed by changes in the transcriptional programme and that both are required to elicit full activation of the mitochondrial stress response. To test this model, the project will aim to identify key factors involved and experimentally delineate the temporal sequence of molecular events that lead to activation of the mitochondrial stress response. The activation of this stress response promotes longevity in the nematode C. elegans and protects against pathogen attacks, highlighting its importance.
Eligibility
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How To Apply
To be considered for this project you MUST submit a formal online application form - full details on eligibility how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/bbsrc-dtp/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
Funding Notes
References
in ageing’, Nature Review Molecular Cell Biology, 19, 109-120(2018).
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