Exploring Synthetic Lethality Interactions through Targeting the SUMO Pathway for Therapeutic Insights

Summary

The School of Molecular and Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.

We especially welcome applications that connect to the School's core research areas, which aim to discover the mechanistic basis of biological functions in health and disease in particular cancer, viral and bacterial infections, protein aggregation disorders and vascular disease.

The project seeks to elucidate intricate cellular processes by systematically targeting genes within the SUMO pathway. The process of SUMOylation, vital for post-translational protein modification, is closely linked to the DNA damage response, offering potential avenues for therapeutic intervention. The project's core involves the creation of a tailored CRISPR library containing single-guide RNAs (sgRNAs) with the precision to disable SUMO pathway components, encompassing SUMO E3 ligases and de-SUMOylating enzymes, within a pertinent cell system. Harnessing this CRISPR library, the project aims to uncover synthetic lethality interactions—instances where the combined loss of SUMO pathway genes and specific DNA damage response genes leads to cellular demise. Methodologically, the project employs molecular biology techniques like synthetic biology cloning for library construction, mammalian cell cultivation, CRISPR library transfection, quantitative real-time polymerase chain reaction (qRT-PCR) to assess gene expression changes, and western blot analysis to gauge protein levels.

The project's goals encompass the development of the CRISPR library, establishment of a relevant cell line, high-throughput screening, and data analysis. These interactions will be evaluated through various methodologies, including qRT-PCR, western blot analysis, and high-throughput immunofluorescence, with a focus on crucial factors in DNA repair, cell cycle regulation, and apoptosis.

The project's significance lies in its potential to bridge fundamental biological insights with practical therapeutic applications. The exploration of synthetic lethality interactions advances understanding of SUMOylation's role in DNA damage response and lays the foundation for innovative therapeutic strategies. The project's outcomes have the potential to unveil novel targets for cancer treatment, leveraging the vulnerabilities of cancer cells with compromised DNA damage response pathways.

For an overview of the faculty visit: https://biologicalsciences.leeds.ac.uk/

For the School of Molecular and Cellular Biology: https://biologicalsciences.leeds.ac.uk/homepage/84/school-of-molecular-and-cellular-biology

Dr. Christian Bassi profile page: https://biologicalsciences.leeds.ac.uk/biological-sciences/staff/2974/dr-christian-bassi

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

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.