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Precision Medicine DTP – Blood flow and solute transport in human placental microvasculature: an in silico approach to stratifying pregnancy pathologies


   School of Engineering

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  Dr T Krueger, Dr M Bernabeu  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Background

The human placenta performs diverse functions later taken on by several different organs. In particular, it mediates the exchange of vital solutes, including respiratory gases and nutrients, between the mother and the developing fetus. The complex heterogeneous structure of the placenta is adapted to perform these various functions. However, despite its availability for ex vivo perfusion experiments just after birth and the importance of placental dysfunction in conditions such as fetal growth restriction, the link between placental structure and function in health and disease remains poorly understood [1, 2].

Recent advances in three-dimensional (3D) imaging have revealed aspects of placental structure in intricate detail [3]. Fetal blood flows from the umbilical cord through a complex network of vessels that are confined within multiple villous trees; the trees sit in chambers that are perfused with maternal blood. Much of the solute exchange between maternal and fetal blood takes place across the thin-walled peripheral branches of the trees (terminal villi) which contain the smallest feto-placental capillaries. Quantitative measurements have demonstrated structural differences between healthy and pathological placentas [1]. However, studies of micro-haemodynamical mechanisms that underpin the pregnancy diseases, such as pre-eclampsia and fetal growth restriction, have so far been confined mainly to studies on two-dimensional histological data [2]. Little is known about how the elaborate and irregular 3D organisation of capillaries within terminal villi, the primary functional exchange units of the feto-placental circulation, contributes to solute exchange in health and disease.

The research will employ a state-of-the-art 3D imaging catalogue of placental microstructure to derive theoretical models of solute transport. The output of 3D confocal microscopy and synchrotron X-ray micro- computed tomography covers unprecedented range of spatial scales, from 1 μm to 1 cm [3], which will aid in the design of computational models. The structural datasets will be complemented by the linked anonymised clinical characteristics from Tommy’s UK National Reproductive Health Biobank (St Mary’s Hospital, Manchester, https://www.tommys.org/research/research-centres/tommys-national-reproductive- health-biobank).

Aims

In this study, we will combine image analysis and computer simulations of blood flow as a suspension of deformable blood cells [4] to examine the dependence of solute transport on the geometrical arrangement of capillaries within terminal villi of the placenta. The properties of these functional exchange units will be quantified and encapsulated in a general theory of placental transport that links complex 3D structure of placental microvascular networks to their solute exchange capacity. Particular emphasis will be placed in understanding how these mechanisms are compromised in pathological placentas taking advantage of recorded clinical endpoints. Future studies will investigate how this theory can complement current imaging modalities used for the risk-assessment and diagnosis of pregnancy complications in vivo.

Training outcomes

The student will receive state-of-the-art training in the core disciplines of image analysis, computational modelling, and physiology while gaining expert knowledge in the context of placental research. This highly interdisciplinary approach is well aligned with the “T-shaped researcher” training requirements identified as key in the DTP in Precision Medicine. The student will develop the essential soft and domain-specific skills necessary to design and implement novel quantitative and computational methods that could solve challenging problems across the entire spectrum of cardiovascular medicine both in academic and industrial settings.

Q&A Session

If you have any questions regarding this project, you are invited to attend a Q&A  session hosted by the Supervisor(s) on 6th December at 1pm (GMT) via Microsoft Teams. Click here to join the meeting.

About the Programme

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.

Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the following link: 

https://www.ed.ac.uk/usher/precision-medicine/app-process-eligibility-criteria  

For more information about Precision Medicine visit:

http://www.ed.ac.uk/usher/precision-medicine


Funding Notes

Start: September 2023

Qualifications criteria: Applicants applying for an MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualification, in an appropriate science/technology area. The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £17,668 (UKRI rate 2022/23).

Full eligibility details are available: http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

Enquiries regarding programme: [Email Address Removed]

References

[1] Jensen OE & Chernyavsky IL (2019) Blood flow and transport in the human placenta. Ann Rev Fluid Mech 51:25.
[2] Zhou Q, et al. (2022) Micro-haemodynamics at the maternal-fetal interface: Experimental, theoretical and clinical perspectives. Curr Opin Biomed Eng 22:100387.
[3] Tun WM, et al. (2021) A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta. J R Soc Interface 18:20210140.
[4] Zhou Q, et al. (2022) Red blood cell dynamics in extravascular biological tissues modelled as canonical disordered porous media. Interface Focus (in press) preprint: https://www.biorxiv.org/content/10.1101/2022.06.18.496666v1

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