Keywords: Biologics; Drug Delivery; Chemical Biology; Bioanalysis
We are seeking a PhD student to develop next-generation antibody conjugates for cell specific targeting. Ideal applicants will have experience in cell biology/biochemistry and/or analytical chemistry. This PhD project will be based at the University of Strathclyde and is funded by GSK, providing the opportunity for you to spend some time at the GSK site in Stevenage and gain industrial experience.
The predominant application of antibody-drug-conjugates to-date has been in the oncology domain, with >100 candidates under development by the pharmaceutical industry. The success of this approach has been due to the differential expression patterns of cell surface receptors, in healthy and diseased tissue, enabling the targeted delivery of small molecule cytotoxic payload. Once internalized by cells (typically via endocytotic pathways), cargo is then released by metabolic degradation of the conjugate to release the cytotoxic payload. Whilst this success as a chemotherapeutic platform has been demonstrated, there is a growing need for the cell selective delivery of non-cytotoxic payloads for indications beyond oncology. Pertinent disease indications such as metastatic breast cancer, glioblastoma and inflammatory conditions (e.g., rheumatoid arthritis) , which are typically associated with poor patient prognosis.
However, expanding the application of ADCs or antibody themselves to engage with intracellular targets is contingent on endosomal escape. We propose to explore the fundamental basis of cellular uptake, distribution and toxicity of antibody conjugates. The goals of this studentship are to, (i) define the molecular determinants of endosomal escape for an antibody conjugate, and (ii) use this information to deliver non-cytotoxic molecular payloads intracellular into target cell types. This project will be a collaboration between the Rattray and Burley groups, and will involve the development of a modular approach to explore how cell penetrating peptides and endosomal escape modulators influence cell uptake, release and distribution within a range of cell types.
This project is ideally suited to highly-motivated and talented students with a keen interest in working at the interface of drug delivery and analytical disciplines. This prestigious project is a collaboration between the Rattray and Perrie laboratories situated within the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), which is also host to the Engineering and Physical Sciences Research Council Multiscale Metrology Suite for Next Generation Health Nanotechnologies.
Training Environnment
The successful candidate will receive training on a wide range of highly desirable technical skills in biopharmaceutical design ranging from bioconjugation and linker chemistry, antibody and peptide chemistry, in the Burley research team. The student will also receive training in bioanalytical skills for the in vitro analysis (high-resolution analysis of oligomer and fragment content and cellular uptake) of antibody-drug conjugate evaluation in the Rattray research team.
This is a collaborative University of Strathclyde and GlaxosmithKline (GSK) studentship. The successful candidate will spend at least three months working alongside the antibody-drug conjugate team at the GSK Stevenage site.
The successful candidate will also benefit from a Postgraduate Certificate in Academic Practice from the University of Strathclyde. The student will benefit from working and interacting with the staff and students in two highly-vibrant and multidisciplinary teams within the Strathclyde Institute of Pharmacy and Biomedical Sciences and Pure and Applied Chemistry interdisciplinary environments.
How To Apply
The applicant should be motivated new research questions as part of a wider multidisciplinary team working at the interface between chemistry, analytical and biomedical sciences.
Applicants are encouraged to send a covering letter explaining their motivation to study for this project, including their suitability for this PhD project, a full Curriculum Vitae and the names (including contact details) of at least two academic or industry-based references by the advertised deadline.
Interviews are expected to take place approximately 3-5 weeks after the closing date for applications. The interview will be held at the University of Strathclyde, or via teleconference if an in-person interview is not practical.
The studentship will commence on October 2nd 2023.
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