Aneuploidy and large-scale chromosomal duplications are common characteristics of many cell lines, including those derived from cancers. Despite these large-scale genome changes, these cell lines remain viable. Cellular processes that buffer against the effects of gene duplication and deletion are therefore key to cell viability. MicroRNAs are short RNA molecules that modulate gene function through translational repression, and are frequently characterised as buffers for gene dosage. This project will use a combination of computational and genetic approaches to study the roles of microRNAs as buffers of gene and chromosome duplications. We will analyse available genomes of cell lines for common losses and duplications of protein-coding genes and microRNAs, and available transcriptomic data as a source of gene and microRNA expression data. We will ask the following questions:
1. Are common sets of protein-coding and microRNA genes duplicated or lost in diverse cell lines?
2. Are genes that are duplicated or lost in cell lines more or less likely to be targeted by microRNAs?
3. What is the effect of duplication of microRNA and/or target gene on their expression levels?
We will manipulate the expression of both microRNAs and their target genes, simulating the effects of gene duplication, in cell lines derived from animal model systems. A variety of assays will be used to assess the contribution of both microRNA and target genes to buffering gene duplication and aneuploidy. Understanding how microRNAs buffer the consequences of aneuploidy will provide key insights into cell viability, including in diseases such as cancer, and the consequences of gene duplication.
https://www.sgjlab.org/
https://www.research.manchester.ac.uk/portal/matthew.ronshaugen.html
Entry Requirements
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.
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
How To Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
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/
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