Intracellular protein delivery is key to probing important cellular processes and developing advanced biotherapeutics. However, protein trafficking into the cell, and more specifically to the cytosol remains a significant challenge. Recently, cyclic oligochalcogenides, through interaction with exofacial thiols, have been found to enhance cellular association, facilitate internalisation via an endocytosis-independent mechanism, and release cargo preferentially in the cytosol. Despite being an advanced modality of synthetic protein-transporters, the nature of their interactions on protein cargo and impact on intracellular delivery remains unclear. Elucidating how synthetic protein-transporter binding interactions influence cellular uptake can provide new insights to further enhance intracellular protein delivery.
The proposed PhD project will focus on establishing structure-cellular uptake relationships of synthetic protein transporters for optimised intracellular delivery. The scientific approach of this project is based on biomimicry, where a library of synthetic protein transporters using cyclic oligochalcogenides will be synthesised with heterogeneous surface properties. Correlation between structural effects of synthetic protein transporters and cellular internalisation will lead to a predictive understanding of how to design synthetic protein constructs for efficient and targeted intracellular delivery. This project is particularly well suited for candidates with an interest in protein modification and chemical biology to advance biological research and drug development.
Applicants should have a 1st or 2.1 honours degree (or equivalent) in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, Engineering, or a closely related discipline. Students who have a 2.2 honours degree and a Master’s degree may also be considered, but the School reserves the right to shortlist for interview only those applicants who have demonstrated high academic attainment to date.
Postgraduate Research applicants must have applied to Queen’s, via the Direct Applications Portal.
Training will be provided in a range of techniques including chemical synthesis and characterisation, bioconjugation, protein structural and functional characterisation techniques and cellular imaging. The student will also develop generic research skills in scientific writing, literature reviewing, time management and delivery of presentations, nationally and internationally.
The PhD student will be encouraged to engage in a variety of impact activities, disseminate the research project findings through publications, public talks, and participate in QUB showcase events.