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Using markers of gene evolutionary age to identify function within gene regulatory networks related to embryo implantation


   Faculty of Biology, Medicine and Health

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  Dr A Stevens, Dr Peter Ruane, Prof M Westwood  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Healthy ageing starts from conception. Environmental influences during early development affect the risk of developing chronic diseases in later life and impact a healthy ageing trajectory. This project will determine how recent evolutionary history has impacted human embryo implantation. The identification of the elements of the implantation process most influenced by recent human specific evolutionary pressure will generate insight into the critical periods during early development where an early embryo is vulnerable to environmental impact. The data generated in this project will support the aim of understanding the mechanistic basis of lifespan and healthy ageing using human systems, with the long-term objective of promoting health in later life, by identifying 'critical periods' during the lifespan which may be particularly susceptible to biological influences/exposures. 

Successful implantation relies upon synchrony between a competent blastocyst and receptive endometrium. Molecular networks mediating these events at implantation are not well understood in humans. However, tracing back the evolutionary origin of modifications that occurred in these networks and pinpointing human-specific changes could provide further insight. 

We have recent data to suggesting that the interactome of the endometrial surface is enriched for evolutionarily older genes but that the embryonic compartment (epiblast) is enriched for genes related to more recent human evolution. Subpopulations of the trophectoderm, the layer surrounding the epiblast, demonstrated a strong relationship with human specific evolutionary markers. Little is known about the function of these trophectoderm subpopulations. 

Specifically, we will:

1. Generate single cell RNAseq data using endometrial organoid models of implantation to characterise the implantation interactome and define the existence of associated cell subpopulations.

2. Perform a multi-level integrated ‘omic analysis of embryo implantation combining transcriptomic with proteomic data and epigenomic data.

3. Use our integrated model of multi-omic interactions occurring during implantation as a basis to assess the impact of recent human evolution.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject.  Candidates with experience in computational biology or with an interest in evolutionary mechanisms are encouraged to apply.  

How to Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD title.

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 www.internationalphd.manchester.ac.uk

Equality, Diversity & Inclusion

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/


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee.
Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

References

Systems based analysis of human embryos and gene networks involved in cell lineage allocation
Smith, H. L., Stevens, A., Minogue, B., Sneddon, S., Shaw, L., Wood, L., Adeniyi, T., Xiao, H., Lio, P., Kimber, S. J. & Brison, D. R., 2019, BMC Genomics. 20, 1, 171.
Identification of the functional pathways altered by placental cell exposure to high glucose: lessons from the transcript and metabolite interactome
Hulme, C., Stevens, F., Dunn, W., Heazell, A., Hollywood, K., Begley, P., Westwood, M. & Myers, J., 27 Mar 2018, Scientific Reports. 8(1):5270.
PT Ruane, C Buck, PA Babbington, W Aboussahoud, SC Berneau, M Westwood, SJ Kimber, JD Aplin, D R Brison. The effects of hyaluronate-containing medium on human embryo attachment to endometrial epithelial cells in vitro. Human Reproduction Open (202019) ; 2020(2): hoz033In Press
PT Ruane, R Koeck, SC Berneau, SJ Kimber, M Westwood, DR Brison, JD Aplin. Osmotic stress induces JNK-dependent embryo invasion in a model of implantation. Reproduction (2018) 156: 421-418.
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