Pyruvate dehydrogenase E2 complex

This project is now closed

The Mechanism of Mitochondrial DNA Replication

Project supervisor: Ian Holt (Virology)

We have recently identified a unique mechanism of replication that occurs in mitochondria. It entails the incorporation of processed transcripts on the lagging strand, as the leading strand of DNA is synthesized. The reason for this exotic behaviour is not known, although it may serve to prevent collisions between transcription and replication complexes, which can cause genomic instability.

The aim of the project is to identify factors involved in the incorporation of RNA into replicating molecules. In addition to the mechanistic insight gained, the new knowledge will be used to design means of interfering in the process of RNA incorporation, in order to clarify its importance for productive and faithful mitochondrial DNA replication. The student will begin by silencing genes implicated in mitochondrial RNA metabolism, in particular RNA helicases and proteins with the ability bind to both RNA and DNA. The effect of RNA interference on mtDNA replication will be determined using standard techniques of the host laboratory, and this will form the platform for more detailed studies of the most promising candidates. These will include, 1) introducing wild-type and mutant versions of the proteins into isolated mitochondria to determine directly their impact on mtDNA replication. 2) tagging the genes in human cells. 3) analysing knockout mice.

Further information about this project is available from Dr Holt

The post is a MRC studentship funded for four years from October 2013, and the stipend is £20,000 per annum including London allowance. Eligibility criteria apply

To apply please download and complete the application form from the downloads section on the right-hand side. This position will remain open until a suitable applicant is appointed. Please apply early to avoid disappointment. Due to the high volume of applications we receive we are unable to provide feedback. If you do not hear from us within three weeks of application you have not been successful on this occasion.

Completed application forms should be returned to student@nimr.mrc.ac.uk

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