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PROJECT TITLE

Characterisation and downstream signaling of trophoblast extracellular vesicles.

SUPERVISORS

Dr Manu Vatish

Professor Christopher Redman

Dr Wei Zhang


DESCRIPTION OF PROJECT

This outline describes the direction of our trophoblast extracellular vesicle group.

The human placenta constitutively releases small vesicles (larger microvesicles and smaller exosomes) from the syncytiotrophoblast layer of the placenta into the maternal circulation. This is reported to occur from early pregnancy all the way through to delivery. We have recently completed a detailed mass spectrometric and next generation sequencing analysis of trophoblast extracellular vesicles isolated by ex-vivo human placental perfusion. This large dataset has been bioinformatically analysed and a number of key proteins and short RNA/mRNAs have been identified. We now wish to understand what these key proteins and RNAs do. The project will be to characterise these moieties in functional assays using cell lines and animal models. The molecular identities are currently being intellectually protected and preliminary evidence suggests that a number of these molecules are disease related and metabolically active. The potential to generate diagnostically or therapeutically important data is high. For this reason we have had funding from a number of industrial partners.


TRAINING OPPORTUNITIES

We are a multi-disciplinary, dynamic group based at the Nuffield Department of Women's & Reproductive Health, with strong links to other centres locally (e.g. Oxford Vesicle Group, Weatherall Institute for Molecular Medicine, Target Discovery Institute, Welcome Trust Centre for Human Genetics and the Big Data Institute). Students will be strongly encouraged to publish their work, present at international conferences, attend biweekly group meetings, journal clubs, as well as departmental seminars and training courses. Above projects will be utilizing a broad spectrum of molecular biology methods including placental perfusion, flow cytometry and nanoparticle tracking analysis. Additionally primary cell cultures, high-throughput sequencing (targeted, exome, whole genome, single cell transcriptomics) and Western blotting as well as immunoprecipitation.