Postgraduate research opportunities

Novel Drug Development Technologies for CNS Penetration and Inhaled Delivery

This project will explore the area of protein degradation through the application of proteolysis targeting chimeras (PROTACs) for central nervous system (CNS) and lung targeted therapies. Structural and physicochemical properties of potential PROTAC molecules will be assessed through synthesis and computational design.

Number of places

1

Funding

Home fee, Equipment costs, Travel costs, Stipend

Opens

29 March 2021

Duration

This 4 year studentship is available starting October 2021.

Eligibility

Applicants will have, or expect to obtain, a strong MChem (or equivalent) degree as a requirement of the funding.  Additionally, the position is well suited to students with significant experience in Synthetic Organic Chemistry and Medicinal Chemistry principles, preferably gained through industrial experience.  Applicants should also have a strong interest in working at the interfaces of chemistry, biology and DMPK, as relevant to drug discovery.

Project Details

The degradation of proteins that cause disease has emerged as a key area of scientific interest for drug discovery and is fast becoming established as a promising complementary strategy to traditional small molecule approaches to target inhibition.  PROTACs are the most advanced class of targeted protein degraders, utilising the function of enzymes called E3 ubiquitin ligases (E3 ligases), which catalyse the tagging of proteins for removal from the body.  PROTACs are bifunctional molecules (connected via a linker) in which one end binds to a protein of interest (POI) and the other binds to an E3 ligase, bringing them into close proximity.  This, in turn, catalyses a process that results in natural degradation of the protein.

Whilst PROTAC technology has reached the clinic for the treatment of cancer, currently, there is very limited literature that exists for targeted delivery to the CNS or lung via inhalation.  The aim of this PhD project will be to explore the structural and physicochemical properties of potential PROTAC molecules through synthesis and computational design, with a key focus on permeability for CNS penetration, and solubility and crystallinity for inhaled delivery.  Biological, physicochemical, in vitro ADME and solid state profiling will drive iterative design-make-test cycles with the aim of delivering tool molecules against targets of interest.

In bringing together Academic and Industry supervision, complementary expertise in organic synthesis, medicinal chemistry, and computational chemistry will provide the PhD student with elevated levels of training in the areas of preparative chemistry, medicinal chemistry design, and data analyses.  Overall, this research has the potential to significantly impact the applicability of PROTACs across a wider variety of diseases, delivering increased opportunity to improve patients’ lives.    

Funding Details

This studentship is fully funded by Medical Research Scotland and is fully collaborative with Charles River Research Discovery Services, Saffron Waldon, Essex, UK.  It is expected that the location of the studentship research will be split approximately 50:50 between the Company and the University laboratories.

Supervisor

Professor William J. Kerr

Dr David M. Lindsay

Dr William Esmeiu (Company Supervisor)

Contact us

For enquiries, please contact Dr Laura C. Paterson: laura.c.paterson@strath.ac.uk

How to apply

Please submit your application by e-mail to Dr Laura C. Paterson (laura.c.paterson@strath.ac.uk), which should include:

  • a cover letter, detailing your experience and motivation for PhD studies
  • a CV with two referees’ details included
  • Full transcripts from your undergraduate degree and any previous postgraduate studies
  • Other pertinent information (e.g., publications, awards, and other distinctions)