Translational Human Models for Brain PBPK Modelling and CNS Drug Development

Details

Central nervous system (CNS) drug exposure is difficult to predict because the blood brain barrier (BBB) tightly regulates drug entry via passive permeability and active transporter‑mediated efflux and uptake. Direct measurement of human brain drug concentrations is rarely possible, so there is a need for translational BBB models that generate parameters suitable for physiologically based pharmacokinetic (PBPK) prediction of CNS exposure (1,2).

This project will develop a mechanistic, proteomics‑informed in vitro in vivo extrapolation (IVIVE) framework for the human BBB. The student will work with advanced human-relevant BBB models (including human induced pluripotent stem cells (hiPSC)-derived “BBB‑on‑chip” systems) to generate permeability and transporter data for CNS drugs and then use these data to parameterize and refine a PBPK-brain model to predict drug distribution between plasma and key brain compartments (2,3).

The project is placed within the Centre for Applied Pharmacokinetic Research (CAPKR), an academically led consortium at the University of Manchester that collaborates closely with industry and regulators. The successful candidate will receive training in BBB in vitro systems, quantitative proteomics and PBPK modelling, providing an excellent platform for a career in model-informed CNS drug development.

Entry Requirements:

Applicants are expected to hold (or about to obtain) a minimum upper second class undergraduate honours degree (or equivalent) in pharmacy, pharmacology, biomedical sciences, physiology, biomedical engineering or a related discipline. Experience in cell culture, proteomics/transcriptomics and quantitative pharmacokinetics is highly desirable, and prior exposure to blood brain barrier models, transporter biology, or PBPK modelling would be an advantage.

For application details, visit the Doctoral Academy website: https://www.bmh.manchester.ac.uk/study/research/apply/.

Candidates must contact the Primary Supervisor before applying to discuss their interest and suitability for the project. Select PhD Pharmacy and Pharmaceutical Sciences on the application form.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the following link: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/

Funding Notes

The student will join the Centre for Applied Pharmacokinetic Research (CAPKR) at the University of Manchester, which is an academically led consortium with nine pharmaceutical companies. Being part of CAPKR will provide the student with an exceptional opportunity to interact with a multi-disciplinary research team. The group is an internationally recognised centre of excellence in academic research and training in the areas of quantitative proteomics/transcriptomics, in vitro in vivo extrapolation, PBPK and PK/PD modelling, with strong ongoing interactions with pharmaceutical companies and regulatory agencies (US FDA). The student will have access to the University’s Biological Mass Spectrometry (BioMS) Facility, which will provide expertise and instrumentation for in vitro quantitative proteomics.

Studentship funding is for four years starting January 2027, covering UK tuition fees and an annual stipend at the UKRI rate.