A 3Rs approach to investigate the feto-maternal interface: visualisation of pathogen and antibody in a 3D in vitro human placental model

Description

Immunisation during pregnancy is now recognised as an efficient approach to protect the fetus and/or the infant from life-threatening infection. However, the mechanisms underlying the transmission of pathogens and the transfer of passive immunity from the mother to the fetus remain obscure. The structure that lies at the interface between mother and fetal environment is the placenta, an intricate organ made up of cellular and vascular networks that serve the functions of kidney, lung, gut and liver altogether in order to promote fetal growth and viability. Owing to the ethical issues associated with the study of human pregnancy, a variety of in vivoex vivo and in vitro models have been developed. However, while the in vivo animal models fail to match the structural and/or functional properties of the human placenta, ex vivo human models are impractical, difficult to set up, of limited capability, and in vitro models lack physiological relevance by virtue of their monolayer and/or static set-up. To address these caveats, this project aims to develop a novel and easy-to-set-up in vitro platform that will help reduce and/or replace the use of both murine and non-murine models. Our model will be validated through the analyses of placenta-blood barrier functions and cross-placental transport of pathogens and antibodies using a 3D microfluidic bioengineered platform i.e., the Organoplate® (Mimetas).

Training and techniques: 

3D organoid and tissue culture, confocal and 2-photon microscopy, microbiological and immunological techniques, primary cell cultures, Miles and Misra method, viral propagation and plaque assay, high-throughput immunoassays, gene expression analysis, flow cytometry.

Pastoral support and learning environment

The PhD student will be jointly supervised by Dr Marie Yang, Dr David Turner and Prof Aras Kadioglu, all based at the University of Liverpool. Dr Marie Yang is Research Fellow at the Centre for Global Vaccine Research, Dr David Turner is a David Sainsbury Research Fellow and a Tenure Track Fellow, and Prof Aras Kadioglu is Chair in Bacterial Pathogenesis and Immunity. All 3 supervisors provide complementary expertise and a track record in immunology, imaging and in vitro organoid models.

The PhD student will be encouraged to develop networking skills, build critical thinking into discussions and develop independent ideas and research topics. All 3 supervisors will work together to provide mentoring and career guidance, either directly or via the University of Liverpool PGR Student Career and Mentoring Schemes. The student will also be introduced to professional networks, collaborators, and presented with career opportunities, grants/fellowships/awards. Bi-monthly laboratory group meetings or journal club will be held. Our research group offers a stimulating environment with a mixture of PhD students, postdoctoral scientists and clinical fellows.

The University of Liverpool has a continued commitment to the 3Rs agenda and engages with 3Rs activity on both a local and national level. The UoL 3Rs symposium is offered on an annual basis, and is supported by NC3Rs. The student will be expected to attend these events, as well as showcase our 3Rs activities at other local, national and international meetings.

Please send any enquiries to Dr Marie Yang at 

To apply please send a CV, cover letter and 2 references to .

Availability

Open to EU/UK applicants

Funding information

Funded studentship

This PhD studentship is fully funded by the UK National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Tuition fees and stipend will be covered, in line with the UKRI guidelines (View Website). Access to additional funding will also be available to cover the cost of other related training and development opportunities e.g., conference attendance, overseas research visits, placements with non-academic partners.

Supervisors

References

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Beccari L, Moris N, Girgin M, Turner DA, et al. Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids. Nature. 2018 Oct;562(7726):272-276. doi: 10.1038/s41586-018-0578-0.
Chaguza C, Yang M, et al. Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism. Commun Biol. 2020 Oct 8;3(1):559. doi: 10.1038/s42003-020-01290-9.
Jacques LC, Panagiotou S, et al. Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin. Nat Commun. 2020 Apr 20;11(1):1892. doi: 10.1038/s41467-020-15751-6.
Turco MY, Gardner L, et al. Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature. 2018 Dec;564(7735):263-267. doi: 10.1038/s41586-018-0753-3.