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Effective models for function-structure relationship in complex biological media


Project Description

A complex multiscale relationship between the structure and function is common in many human organs (such as the lung, liver and placenta), and many diseases are associated with an imbalance in the relationship. This PhD project aims to develop new tools to characterise effectively transport in complex biological media, using the human placenta as a motivation and primary application.

The human placenta is a critical life-support system for the developing fetus. The supply of oxygen and nutrients has to be well orchestrated within a complex fetal vascular network packed in irregular trees and surrounded by maternal blood flow, thus forming a disordered porous medium. Placental insufficiency could result in stillbirth or premature delivery, as well as in a higher risk of cardiovascular, metabolic and neurological disorders later in adult life with significant costs to society and healthcare. At the same time, the human placental arrangement is unique, having no close analogues in other species, so theoretical modelling is of particular value. However, the complexity of placenta prevents direct analysis and simulation at the organ level, and there is a lack of established modelling tools to manage the complexity.

This project will use a combination of analytical, statistical and computational approaches to establish how the placental transport of solutes and metabolites interacts with its structure. The models will be informed by unique three-dimensional X-ray tomography datasets acquired in Manchester, which span the spatial scales of 10 microns to 10 mm and reveal structural differences in normal and abnormal placentas. The clinical expertise in ultrasonic Doppler and magnetic resonance imaging will be utilised to validate the developed modelling tools.

The project will suit a student taking a Masters-level degree in applied mathematics, physics, bioengineering or a related area who has enthusiasm to apply their skills to a challenging biomedical application. Candidates are expected to hold (or be about to obtain) a minimum upper second class degree (or equivalent) in a related subject.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

Informal enquiries may be made directly to the primary supervisor.

References

Jensen OE & Chernyavsky IL (2019) Blood flow and transport in the human placenta. Ann. Rev. Fluid Mech. 51:25-47 (doi.org/10.1146/annurev-fluid-010518-040219).

Nye GA, Ingram E, Johnstone ED, Jensen OE, Schneider H, Lewis RM, Chernyavsky IL & Brownbill P (2018) Human placental oxygenation in late gestation: experimental and theoretical approaches. J. Physiol. (in press, doi.org/10.1113/JP275633).

Ingram E, Morris D, Naish J, Myers J & Johnstone E (2017) MR Imaging Measurements of Altered Placental Oxygenation in Pregnancies Complicated by Fetal Growth Restriction. Radiology 285:953-960 (doi.org/10.1148/radiol.2017162385).

Junaid TO, Bradley RS, Lewis RM, Aplin JD & Johnstone ED (2017) Whole organ vascular casting and microCT examination of the human placental vascular tree reveals novel alterations associated with pregnancy disease. Sci. Rep. 7:4144 (doi.org/10.1038/s41598-017-04379-0).

Pearce P, Brownbill P, Janáček J, Jirkovská M, Kubínová L, Chernyavsky IL & Jensen OE (2016) Image-based modeling of blood flow and oxygen transfer in feto-placental capillaries. PLoS ONE 11:e0165369 (doi.org/10.1371/journal.pone.0165369).

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