Genome-scale analysis of topoisomerase activity (2018)

What you get

The scholarship covers:

• UK/EU fees which are paid internally by the School of Life Sciences
• Living costs of £14,777 per year

Type of award

Postgraduate Research (PhD)

PhD project

Background: Topoisomerases function as essential enzymes during DNA metabolism to facilitate DNA replication, transcription, chromosome segregation, and compartmentalisation of the nucleus. A unique feature of their catalytic cycle is the transient cleavage of DNA strands to create covalent protein-linked DNA intermediates. Should the enzyme malfunction during this critical step, persistent protein-linked DNA breaks can arise that are toxic to cell survival—a property which has been exploited to poison cancer cells with inhibitors such as etoposide and camptothecin. A problem of such strategies is the unavoidable increase in the potential for genomic mutations and gross chromosomal rearrangements that may arise both in the cancer cells and any somatic tissue. The indirect impact that topoisomerase inhibition has on transcription and replication via changes in DNA topology and the three-dimensional packaging of chromosomes—and how this may impact genome stability—is also poorly understood.

Project: We recently developed methods to study the genome-wide activity of Topoisomerases in cycling S. cerevisiae and human cells. We are also adept in the analysis of genome-wide chromosome conformation using Hi-C. The proposed PhD project will begin to link together these themes, allowing an exploration of our broad questions that concern the role that topoisomerases play throughout different cell cycle phases to modulate chromosome metabolism and promote genome stability.

Impact: By investigating questions in complementary systems (yeasts and human cells)—selected for their utility to answer particular questions—we expect to gain significant insight into previously unexplored areas of topoisomerase biology.

Eligibility

Candidate must fulfi the follwoing criteria:

•  have a strong background in Molecular Biology and Genetics with additional experience of Bioinformatics
•  recently received an MSc and/or a First or high 2:1 BSc in a relevant subject
• if English is not your first language we require an IELTS score of 6.5 overall, with not less than 6.0 in any section.

Deadline

How to apply

Please submit a formal application using our online application system.

The application must include:

• CV
• degree transcripts and certificates
• statement of interest (must clearly state the project title and name of the supervisor, Dr Matt Neale)
• names of two academic referees
• IELTS Certificate for non-UK candidates
• Scanned copy of Passport  

On the application system use Programme of Study – PhD in Genome Stabilty. The course start date is Feburary 2019. The proposed supervisor is Dr Matt Neale. In the funding section state that you are applying for funding.

Contact us

For enquiries about the application process contact Anna Izykowska (a.izykowska@sussex.ac.uk)

For enquiries about the project contact Matt Neale (m.neale@sussex.ac.uk)