About the Project
This interdisciplinary PhD program addresses a pressing challenge via the development, evaluation and standardisation of a human “placenta on a chip” HPTS, advanced towards a regulated level for use by the pharmaceutical industry to acquire reliable transfer data of test compounds from the maternal to the fetal circulatory systems. The project will appeal to a bioengineering student interested in developing a synthetic human placental barrier and modelling  the transmembrane transfer of compounds in an academic and industrial environment. Human primary stem cell trophoblasts , forming a true syncytiotrophoblast barrier  will be co-cultured with human placental endothelial cells to form a differentiated and polarised placental barrier between opposing maternal and fetal circulatory-phase compartments. Barrier compound clearance studies will be compared to ex vivo data from the human placental dual perfusion model; in vivo animal data; and to known human fetal:maternal plasma ratios for drugs already prescribed in pregnancy. The physical properties of the barrier, including length of diffusional pathway, porosity and fetal-side (acceptor-side) flow will be mathematically modelled for transfer efficacy and tested in the developed barrier system.
The candidate will be expected to work flexibly at all locations to develop skills within the Maternal & Fetal Health Research Centre at St Mary’s Hospital (supervised by Drs Paul Brownbill and Peter Ruane) and the Department of Mathematics (supervised by Dr Igor Chernyavsky) at the University of Manchester; and the Clinical Pharmacology and Safety Sciences Team at AstraZeneca, Cambridge (supervised by Drs Nicola Powles-Glover and Rhiannon David).
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/) .
If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.
Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships
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 https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
1. P. Brownbill, I.L. Chernyavsky, B. Bottalico, G. Desoye, S. Hansson, G. Kenna, L.E. Knudsen, U.R. Markert, N. Powles-Glover, H. Schneider, L. Leach, An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy, Reprod Toxicol 64 (2016) 191-202.
2. O.E. Jensen, I.L. Chernyavsky, Blood flow and transport in the human placenta. Annu Rev Fluid Mech 51 (2019) 25-47. doi:10.1146/annurev-fluid-010518-040219.
3. M. Rothbauer, N. Patel, H. Gondola, M. Siwetz, B. Huppertz, P. Ertl, A comparative study of five physiological key parameters between four different human trophoblast-derived cell lines. Sci Rep 7(1) (2017) 5892. 4.
4. Okae H, Toh H, Sato T, et al. Derivation of Human Trophoblast Stem Cells. Cell Stem Cell. 22(1) (2018) 50‐63.e6. doi:10.1016/j.stem.2017.11.004
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