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

PGR-P-1923

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Non-funded
Additional supervisors
Dr Christian Bassi
Schools
School of Molecular and Cellular Biology
<h2 class="heading hide-accessible">Summary</h2>

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.<br /> <br /> 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.

<h2 class="heading hide-accessible">Full description</h2>

<p>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&#39;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&mdash;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.</p> <p>The project&#39;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.</p> <p>The project&#39;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&#39;s role in DNA damage response and lays the foundation for innovative therapeutic strategies. The project&#39;s outcomes have the potential to unveil novel targets for cancer treatment, leveraging the vulnerabilities of cancer cells with compromised DNA damage response pathways.&nbsp;</p> <p>For an overview of the faculty visit: <a href="https://biologicalsciences.leeds.ac.uk/" rel="noopener noreferrer" target="_blank">https://biologicalsciences.leeds.ac.uk/</a></p> <p>For the School of Molecular and Cellular Biology: <a href="https://biologicalsciences.leeds.ac.uk/homepage/84/school-of-molecular-and-cellular-biology" rel="noopener noreferrer" target="_blank">https://biologicalsciences.leeds.ac.uk/homepage/84/school-of-molecular-and-cellular-biology</a></p> <p>Dr. Christian Bassi profile page: <a href="https://biologicalsciences.leeds.ac.uk/biological-sciences/staff/2974/dr-christian-bassi" rel="noopener noreferrer" target="_blank">https://biologicalsciences.leeds.ac.uk/biological-sciences/staff/2974/dr-christian-bassi</a></p>

<h2 class="heading">How to apply</h2>

<p>To apply for this project opportunity applicants should complete an <a href="https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply">online application form</a> and attach the following documentation to support their application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University&#39;s minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Biological Sciences as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>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. Across all Faculties 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.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

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.

<h2 class="heading heading--sm">English language requirements</h2>

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.

<h2 class="heading">Funding on offer</h2>

<p>This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.&nbsp;</p> <p>&nbsp;</p>

<h2 class="heading">Contact details</h2>

<p>For information about the application process please contact the Faculty Admissions Team:</p> <p>e: <a href="mailto:fbsgrad@leeds.ac.uk">fbsgrad@leeds.ac.uk</a></p>