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2020 NIHR ACF PES Warwick Platform Science and Bioinformatics

 

Contents

2020 NIHR Academic Clinical Fellowship in Priority Research Themes

HEE Local Office: West Midlands
Medical School: University of Warwick
Research Theme: Platform Science and Bioinformatics
Specialty Options: Obstetrics and Gynaecology

Plain English Summary

Aims and background of the research

Second trimester pregnancy loss means loss of a baby between 12 and 24 weeks gestation. These losses occur in about 2% or pregnancies resulting in significant distress to the couples badly wanting a healthy baby. Whilst fetal anomalies are sometimes detected at post-mortem in the majority of cases the cause for the loss in unknown despite post-mortem examination and an investigative screen in the mother.

A potential cause of second trimester pregnancy loss is placental failure. The placenta consists of a contribution from both the mother and the fetus. A theory has been proposed by some senior experts in the field that premature cellular aging (senescence) of the mother’s side of the placenta (decidua) cause some of these pregnancy losses.

The decidua is a complex tissue with multiple cell populations. The decidua originates from from the lining of the womb (endometrium) and starts developing in the second half of the menstrual cycle. Just over half way through a menstrual cycle endometrial cells change into specialised decidual cells and a proportion undergo senescence. It is possible that too many senescence cells renders the decidua unable to support adequate fetal growth.

Design and methods used

The ACF would work in an existing successful team by collecting, processing and analysing samples from women with second trimester loss in the same way that other samples are currently being analysed.
• Patients will be recruited from an established preterm prevention clinic run by Prof Quenby.
• Samples will be stored in the Tommy’s Reproductive Health Biobank (MRC funded).
• High throughput single-cell RNA-seq (scRNA-seq) will be used. This decomposes a complex tissue into thousands of individual cells, identifies transcriptionally distinct cell types and states, and determines the pattern of gene activity/inactivity that characterises each cell population. (Prof Brosens group)
• Single cell sequencing with Drop-seq, which combines droplet microfluidics with massively parallel RNA-sequencing of individual cells. (Prof Brosens group)
• Computational analysis of the data, including method development, is overseen by Professor Ott.

Patient and public involvement

We have links with patient led charities such as the Lily Mae foundation and the ACF would be encourage to seek advice from them.

Dissemination

The ACF would be encouraged to present the data at relevant medical conferences. Write high impact publications and use data for fellowship applications.