Mark Cragg

This PhD project at the University of Southampton focuses on the development of next-generation nucleic acid drugs (NAD) with enhanced delivery and efficacy. Supervised by Dr Afaf El-Sagheer and Prof. Mark Cragg, the research aims to chemically modify NADs to improve their targeted delivery, activity, and safety, addressing key challenges in the field such as efficient cellular uptake and toxicity. Nucleic acid drugs are unique in their ability to target mRNA, offering therapeutic options for diseases that are not accessible by conventional small molecule drugs or antibodies. Despite their promise, challenges remain in delivering these drugs efficiently to cells and tissues, and recent clinical trials have highlighted the importance of balancing efficacy with safety. This project seeks to tackle these issues by synthesizing novel chemical modifications to enhance delivery, particularly to heart and brain tissues, and by evaluating the biophysical and biological properties of the modified oligonucleotides. As a PhD student, you will join a dynamic research group within the School of Chemistry, benefiting from outstanding facilities and a vibrant academic environment. The project is highly interdisciplinary, sitting at the interface of chemistry and biology, and includes opportunities for collaboration with industry and academic labs in Southampton and Oxford. You will receive comprehensive training in solid phase oligonucleotide synthesis, biophysical and biochemical assays (including UV, fluorescence, cell biology, and machine learning), and structural techniques such as X-ray crystallography. Industrial training and visits to collaborator labs are also part of the programme. Applicants should hold a UK 2:1 honours degree or its international equivalent, with essential skills in experimental synthetic organic chemistry. Additional knowledge in oligonucleotide synthesis, biophysical/biochemical assays, and structural techniques is advantageous but not required. The University offers a range of funding opportunities for both UK and international students, including Horizon Europe fee waivers, Presidential Bursaries, and competition-based studentships that typically cover tuition fees and provide a stipend for living costs. The School of Chemistry & Chemical Engineering is committed to equality, diversity, and inclusivity, and welcomes applicants from all backgrounds. Applications are considered on a rolling basis, so early submission is encouraged. For more information and to apply, visit the project page or contact the Faculty of Engineering and Physical Sciences at [email protected] or the project leader at [email protected].