Novel mass spectrometry tools for higher-order structure of siRNA and sgRNA

A highly competitive EPSRC Industrial Doctoral Landscape Award in partnership with AstraZeneca, offering the award of fees, together with a tax-free maintenance grant (£20,780 in Session 2025/26 for full-time study, pro-rata for part-time study).  An additional Top-Up of £4,000 per year for 4 years and further training and support will also be provided.<br /> <br /> This opportunity is open to UK and International applicants. All candidates will be placed into the EPSRC Industrial Doctoral Landscape Award Competition and selection is based on academic merit.

<p><strong>The Project</strong></p> <p>Oligonucleotides are an important class of biomolecules but until recently somewhat neglected in structural biology research. Well-known functions range from storage of inherited information to gene regulation; but short DNA and RNA sequences can also provide interaction motifs for proteins and antibody-like high-affinity binding (aptamers). There is now a surge of interest in oligonucleotides in pharma and vaccine research, and an urgent need to have better methods to characterize their 3D structures and how they fold. Currently our insights and tools are limited: many of the interesting sequences are either too small or too flexible for structural biology methods such cryo-electron microscopy. In this EPSRC CASE project with Prof. Frank Sobott (Faculty of Biological Sciences) at the University of Leeds and AstraZeneca (Macclesfield, UK), you will develop and apply new methods based on structural mass spectrometry (MS) to characterize structure and function of oligonucleotide formats of pharmaceutical interest. </p> <p><br /> Structural MS has become a breakthrough technology for biomolecular characte¬ri¬zation over the last two decades. It can link information on small changes in the sequence with 3D structure (folding) and interactions and deliver exceptional insights e.g. into intrinsic disorder and lipid interactions. While not actually providing high-resolution images, structural MS approaches such as native MS, ion mobility, chemical crosslinking, covalent labelling, and hydrogen-deuterium exchange can nevertheless characterize dynamic and hetero¬geneous distributions of conformational states and interaction stoichiometries, and capture complex conformational behaviour. These methods are often used together with computational modelling and, increasingly, machine learning, which you can also explore in this project. While some work has already been done with native MS and ion mobility (which determines molecular size and shape) to study structure and interactions of aptamers, G-quadruplexes and DNA nanostructures, but there is much left to understand and explore. Interested? You could be that explorer!<br />  </p> <p><strong>Why study your PhD at Leeds? </strong></p> <p>Study in an active research environment: Studying your PhD with us means you’ll be working in a professional research environment, using UK-leading facilities to bring your project to life – alongside active researchers who are at the forefront of their area. </p> <p>A strong network of support : The Leeds Doctoral College connects our community of researchers and can offer you the guidance, services and opportunities you’ll need to get the most out of your PhD. </p> <p>Close industry links: Our partnerships and links to companies and academic institutions give you the opportunity to network at industry talks, seminars and conferences, building connections that'll benefit your next steps after you complete your PhD. </p> <p>Professional skills development: We think of the whole picture at Leeds. That’s why we offer a range of workshops and courses that'll enhance your skillset further and transfer into your professional career. </p> <p>Personal and wellbeing services: Mental health and wellbeing support are integral to who we are at Leeds. You’ll have access to the full range of services we offer to ensure you’re feeling your best – and reaching your potential in your studies. </p> <p>Join our global community: We welcome students, researchers, academics, partners and alumni from more than 140 countries, all over the world. This means, as a university, we’re bringing together different cultures and perspectives which helps strengthen our research – and societal impact. </p>

<p>Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the research information section that the research degree you wish to be considered for is <strong>Novel mass spectrometry tools for higher-order structure of siRNA and sgRNA</strong> as well as<strong> Professor Frank Sobott </strong>as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University'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>

Applicants to this studentship in the Faculty of Biological Sciences 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.

<p>For further information please contact the Graduate School Office<br /> e: fbsgrad@leeds.ac.uk</p>