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WR DTP project: Prevention of DNA replication and transcription machinery conflict: how do helicases help?


Department of Biology

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Dr M Hawkins , Prof D Barilla No more applications being accepted Competition Funded PhD Project (Students Worldwide)
York United Kingdom Biochemistry Biophysics Genetics Microbiology Molecular Biology

About the Project

DNA replication is a crucial process for life. Genomes need to be duplicated in order for cells to divide and organisms to grow. Though the replication process is vital it does not always proceed smoothly. A common problem is that DNA replication forks can be blocked when they collide with obstacles such as proteins bound to DNA. Blockage of essential DNA replication forks can lead to genome instability and cell death. Despite this being a problem shared by all life, we do not understand exactly how multiple rescue pathways contribute to uninterrupted DNA replication.

In bacteria DNA replication occurs at the same time as transcription of genes. Therefore the most common obstacles for bacterial replication forks are transcribing RNA polymerases. If the molecular machines responsible for reading and copying DNA collide with each other it can disrupt both processes.

This project aims to determine the molecular mechanisms that reduce and resolve conflict between the essential biological processes of DNA replication and transcription. We will use Escherichia coli as a model organism and focus on helicases that promote the replication of transcribed DNA. Bacterial replication forks can be reconstituted in a tube and the student will use this to biochemically investigate replication blocks and their consequences. This project will also involve the characterisation of protein-protein and protein-DNA interactions through training in cutting edge techniques. Combining biochemical, biophysical and genetic approaches will ensure a successful project that will address fundamental questions about DNA replication.

The White Rose DTP in Mechanistic Biology is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Funding Notes

This project is part of the BBSRC WR DTP in Mechanistic Biology. Appointed candidates will be fully-funded for 4 years. The funding includes:
Tax-free annual UKRI stipend (£15,285 for 2020/21)
UK tuition fees (£4,473 for 2021/22)
Research support and training charges (RSTC)
We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

ENTRY REQUIREMENTS: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. If English is not your first language, you will need to meet the minimum entry requirements for your country. Please check our website: https://www.york.ac.uk/study/postgraduate-research/apply/international/english/

START DATE: 1st October 2021
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