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An in-vivo but non-animal test system for cell recruitment and cell integration into the heart


Project Description

Applications are invited for a fully-funded three year PhD to commence in October 2020.

The PhD will be based in the Faculty of Science and Health, and will be supervised by Dr Susanne Dietrich, Dr Anthony Lewis and Dr Aikaterini Lalatsa who will combine their expertise in heart development, heart beat control and cell-supporting biomaterials.

The work on this project involves:
● Making novel discoveries underpinning therapy development by unravelling
- how cells are recruited and integrated into a beating heart,
- how cells are instructed to follow a pre-existing heart beat;
● Testing novel biomaterials – can biomaterials support cell delivery to the heart ?
● Learning / applying a wide range of laboratory techniques including cell and embryo culture, techniques to monitor gene/ protein expression profiles, various microscopical techniques and biomaterials preparation
Project description (max 300 words)

Cardiovascular disease is the most prevalent cause of death, because it frequently leads to a fatal stroke or heart attack. In a heart attack, blood and oxygen supply to the beating heart cells becomes obstructed, and as a consequence, heart muscle cells perish. Current efforts aim to develop therapeutic cells that can replace the lost cells and restore heart function. This however has not been achieved because exogenously generated cells fail to integrate into the framework of the existing heart and to beat in tune, causing potentially fatal arrhythmias (1).

In the embryo, a cell population exists that is recruited and integrated into the primitive, already beating heart (2). How the integration of these so-called secondary heart field cells is facilitated is not known. This project will use the chicken embryo in the egg as an in-vivo but non-animal test system for cell recruitment and cell integration into the heart. The project will first investigate, how cell recruitment and integration works. Thereafter, the project will establish whether tissue-culture-grown, potential therapeutic human cells can integrate into the primitive heart in the same fashion as the normal embryonic cells.

To monitor cell recruitment, fluorescently labelled cells will be transplanted into the secondary heart field of early stage chicken embryos; cell contribution to the heart and cell beating will be assessed by fluorescence videomicroscopy. To monitor cell integration, changes in marker gene expression, cell shapes and cell-to-cell contacts will be recorded, using in situ hybridisation and immunohistochemistry, alongside quantitative methods such as qPCR. A particular focus will be on the expression of ion channels that control beating. To develop a platform for the evaluation of human cells, biomaterials will be tested for their ability to present the cells to the existing heart for recruitment (3).


General admissions criteria
You’ll need an upper second class honours degree from an internationally recognised university or a Master’s degree in an appropriate subject. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

Specific candidate requirements
Experience in cell/ developmental biology is desirable.

How to Apply
We’d encourage you to contact Dr S. Dietrich () to discuss your interest before you apply, quoting the project code.

When you are ready to apply, you can use our online application form. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our ‘How to Apply’ page offers further guidance on the PhD application process.

If you want to be considered for this funded PhD opportunity you must quote project code PHBM4711020 when applying.

Funding Notes

The bursary is available to UK and EU students only and covers tuition fees and an annual maintenance grant of £15,009 (UKRI 2019/20 rate) for three years. Bursary recipients will also receive up to £1,500 per year for research project costs, as well as office space and computing facilities.

References

(1) Scuderi, G.J. and J. Butcher, Naturally Engineered Maturation of Cardiomyocytes. Front Cell Dev Biol, 2017. 5: p. 50
(2) Wittig, J.G. and A. Munsterberg, The Early Stages of Heart Development: Insights from Chicken Embryos. J Cardiovasc Dev Dis, 2016. 3(2).
(3) Moshayedi, P., et al., Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials, 2016. 105: p. 145-155.

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