Physiology and mathematical modelling of pharmacodynamics in the human placenta

About the Project

Medicines regulators are calling for new alternative methods to replace animal testing of in the safety evaluation of pharmaceuticals prescribed to women of childbearing age. The ex vivo dual perfusion model of the human placenta provides an ethical potential to study drug uptake and transfer from the maternal to the fetal circulation. This model requires further developmental steps to bring the technology to acceptable through-put speed for toxicology testing, without compromising on the quality control of test data. It also provides useful tools in the development of mathematical models to understand the efficacy and mechanisms of uptake processes of traditional compounds and biopharmaceuticals.

This self-funded PhD opportunity will investigate the complexities of hydrostatic pressure differences and transplacental barrier “leaks” of fetal perfusate using the ex vivo dual perfusion model of the human placenta. The effects of these “leaks” will be mathematically modelled for the counter-current maternal-side to fetal-side transfer of inert compounds and medications across the barrier. It requires a candidate with a deep interest in biological mechanisms and placental anatomy and a preparedness to learn physiological techniques of the human placenta alongside analytical and computional model development. On call work will be required to follow with experimentation on freshly delivered placentas from maternal disease.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in a related area/subject. Candidates with experience in physics or mathematics, or with an interest in pharmacology and mathematical modelling are encouraged to apply.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Developmental Biology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

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 website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester)

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website View Website

References

• Schneider H, Brownbill P, Albrecht C (2021) Ex vivo dual perfusion of an isolated cotyledon 1 of human placenta: history and future challenges. Placenta 107: 8–12.
• Schneider H, Albrecht C, Ahmed MS, Broekhuizen M, Aengenheister L, Buerki-Thurnherr T, Danser AHJ, Gil S, Hansson SRi, Greupink R, Lewis RM, Markert UR, Mathiesen L, Powles-Glover N, Wadsack C, Brownbill P (2022) Ex vivo dual perfusion of an isolated human placenta cotyledon: towards protocol standardization and improved inter-centre comparability. Placenta 126:83-89
• Brownbill P, Sebire N, McGillick E, Ellery S, Murthi, P (2018) Ex Vivo Dual Perfusion of the Human Placenta: Disease Simulation, Therapeutic Pharmacokinetics and Analysis of Off-Target Effects. In: Methods in Molecular Biology – Preeclampsia Eds: Vaillancourt, C. & Murthi, P. (eds.). 1 ed. Switzerland: Springer/Humana Press, Vol. 1710, p. 173-189 16 p. 14. (Methods in Molecular Biology)