Uncovering the dynamics of SUMOylation in DNA replication

Applications are invited for a 3.5-year postgraduate studentship in the newly established SUMO biology lab in the School of Molecular and Cellular Biology, University of Leeds.

DNA replication needs to be tightly regulated to maintain genomic stability. Defective DNA replication is a pervasive feature of many human diseases including cancer. Post translational modifications (PTMs) of proteins involved in DNA replication are essential for their correct function. This project will focus on the role of SUMO1-3 (small ubiquitin-like modifiers 1-3) which are conjugated to multiple proteins involved in DNA replication. While many SUMOylated DNA replication factors have been catalogued, we no little of how the SUMOylation of these factors is regulated. SUMOylation is a highly dynamic process, at least in part due to a small family of SUMO proteases (SENPs) which rapidly and specifically remove SUMO from substrates. This project will use human and mouse cells that are deficient in SENPs as a model of disrupted SUMO dependent DNA replication biology. SENP deficient cells show hallmarks of defective DNA replication which results in increased genomic instability. How individual SENPs modulate DNA replication is yet to be established. 

The project aims are:

·   Characterise the DNA replication defects in human and mouse cells deficient in SENP protease activity.

·   Identify the cellular and genomic consequences of defective deSUMOylation.

·   Use novel proteomic approaches to identify SENP interactors and substrates relevant to DNA replication signalling.

The student will gain expertise in various cellular and biochemical assays (SUMOylation assays, FACS, Immunofluorescence, generation of stable cell lines, CRISPR-Cas9 gene editing and karyotyping). The student will also gain experience in assays of DNA replication fork dynamics such as the DNA fibre assay, and proteomic identification of SUMOylated substrates and SENP interactors.

Eligibility

Applicants should have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. A Masters degree is desirable but not essential.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

How to apply

To apply for this scholarship opportunity applicants should complete an online application form and attach the following documentation to support their application

• a cover letter 
• a full academic CV
• degree certificate and transcripts of marks
• Evidence that you meet the University's minimum English language requirements (if applicable)

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

• Select PhD in Biological Sciences as your programme of study
• Give the full project title and name the supervisors listed in this advert
• For source of funding please state you are applying for an advertised Faculty Scholarship

As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Within the Faculty of Biological Sciences we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+; and people with disabilities. Applicants will always be selected based on merit and ability. 

For further information about this scholarship please contact the Faculty Admissions Team

e: [Email Address Removed]

For more specific project queries please contact Dr Garvin and Dr Zeqiraj directly;

e: [Email Address Removed]

e: [Email Address Removed]