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EASTBIO The fight for space: how do transcription and DNA replication co-exist

   School of Biological Sciences

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  Dr S Buonomo, Prof Meriem El Karoui  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Two processes essential to life, DNA replication and transcription, share the same substrate, the chromatin. However, the encounter of the advancing replication fork with the transcription machinery stalls the progression of DNA replication. Head-to-head collisions may result in the formation of DNA-RNA triple helices, R-loops, DNA damage and genomic instability. An increase in transcription-replication collision is causative of several human diseases, from cancer to neuropathies. To minimise these collision, prokaryotes and lower eukaryotes favour the co-orientation of gene transcription with replication. However, in the larger genomes of multicellular organisms this strategy can only account for a minor part of the solution. Preliminary evidence from the Buonomo lab suggests that a very efficient strategy to allow transcription and DNA replication to share the same substrate is to ensure that they do not find themselves in the same place at the same time. The aim of this project is to investigate the role of the DNA replication-timing program in guiding a new molecular mechanism to regulate genome stability. The Buonomo lab has discovered the only known genome-wide regulator of the DNA replication timing program, that ensures that every genomic segment is replicated at the right time and in the right place in the nucleus. We will use mouse embryonic stem cells as a model system and employ state of the art technologies, both at the population level (nascent RNA seq, high-resolution repli-seq, nanopore sequencing) and at the single cell level (high resolution microscopy and three-dimensional fluorescent in situ hybridisation). This project represents an unique opportunity to develop data analysis skills both in genomics and image analysis, under the expert guide of Prof. El Karoui, in combination with acquiring a expertise in a wide range of both advanced cellular and molecular biology in the Buonomo lab.

The School of Biological Sciences is committed to Equality & Diversity:

The “Institution Website” button will take you to our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate (£17,668 annually in 2022) and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants, however any Visa or Health Insurance costs are not covered. UKRI eligibility guidance: Terms and Conditions: International/EU:

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