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Transcription-replication crosstalk


Project Description

A PhD project is available within the Midlands Integrative Training Partnership (MIBTP) in the laboratory of Dr Marco Saponaro, to investigate in details the crosstalk between RNA Pol II transcription and DNA replication.

RNA Pol II transcription and DNA replication are the two essential processes that use as a substrate the DNA in our cells. This allows cells to express the content of their genetic information, and to propagate these instructions on to daughter cells. However, DNA can be engaged only by one of these processes at any given time. Therefore, transcription can impair DNA replication inducing DNA damage and genome instability. In contexts of defective transcription this instability is furthermore greatly increased. Importantly, transcription-induced genome instability has also a direct impact on human health, as associated with cancer development and neurological disorders. We have now uncovered the first details of how exactly transcription and replication affect each other, and want to expand our understanding characterising further the crosstalk between these two processes.

Aims of the project and methods:

For all these reasons, we are interested in investigating further the relationship between RNA Pol II transcription and DNA replication using a systemic approach
i) Genome-wide next generation sequencing analyses of both transcription and DNA replication;
ii) Cell biology studies to characterise the impact of the interference between transcription and replication on genome stability (immune-fluorescence staining of DNA damage sites, activation of the DNA damage response by immunoblotting);
iii) Functional studies to characterise the roles of factors involved in coordinating, and resolving conflicting situations, between these two processes (impact of the RNAi of specific factors on genome-wide coordination between transcription and replication and on the DNA damage levels).
As this is a problem at the basis of cell biology, understanding the fine details this crosstalk has broad ranging relevance for cell biology as well as human health.



Applicants should have a strong background in molecular and cellular biology, with an interest in genome stability maintenance and interested in learning novel genomic approaches. For more details about the project and the research going on in the supervisor lab, please contact me directly at .

If you are interested in a PhD project at the University of Birmingham, please apply to the relevant department / school depending on your project selection.

Please also notify MIBTP of your application by completing the online application notification form.https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/submission/

Funding Notes

For the full details about length and characteristics of the MIBTP programme please visit this website
View Website

References

Saponaro et al., RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. Cell 2014; doi: 10.1016/j.cell.2014.03.048
Williamson et al., UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene. Cell 2017; doi:10.1016/j.cell.2017.01.019

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