Tommy's Reproductive Health Biobank

The Tommy's charity exists to save babies' lives, funding research into the causes and prevention of pregnancy complications that lead to miscarriage, stillbirth and premature birth. Tommy's also provide pregnancy health information for parents-to-be.
Tommy's fund research in four centres of excellence:
The Tommy's National Centre for Miscarriage Research (Warwick, Imperial, Birmingham)
The Tommy's Maternal and Fetal Research Centre in St Thomas's London
The Tommy's Maternal and Fetal Research Centre in Edinburgh
The Tommy's Maternal and Fetal Research Centre in Manchester

Research is aimed at understanding reproductive pathology so that baby's lives can be saved. Each day in the UK, 2,127 babies are born, 10 babies are stillborn, 648 babies are miscarried and 152 babies are born preterm. Often clinicians are not able to give couples causes for their pregnancy losses, so Tommy's exist to find causes and prevent these deaths. However, there is a limit to what Tommy's charitable fund raising can achieve, and by the terms of Tommy's mission, they prioritise funding for research that has the potential to deliver new diagnostics and treatments, not funding for the development of research infrastructure.

The goal of the proposed Tommy's Reproductive Health Biobank is to augment and enhance six existing biobanks at four Tommy's funded centres, to provide added value for research. The biobank will be unique in combining expertise from these centres, four of the largest reproductive health research groups in the UK, into a single functional unit of international significance. The samples comprise of tissues obtained before pregnancy, at the time of miscarriage or during complex pregnancies, as well as in normal pregnancy. Clinical data will be linked to the samples using advanced soft-ware technology. Tommy's Net is a software package and a server recently developed using funding provided by the Tommy's charity. Tommy's Net contains information on couples with recurrent miscarriage that consent. It is also able to link this information to other test results, samples and pregnancy outcome details held on other NHS databases. The MRC biobank funding will allow data on other pregnancy complications to be stored in the same way in the same system. As part of Tommy's Biobank, we will build on the Tommy's Net system to provide a registry of databases for historic collections, and a combined database using an agreed dataset for each sample collected in the future. This linked biobank will allow samples from each site to be characterised and tracked, and make them more accessible to the wider research community.

The Tommy's Reproductive Health Biobank aims to facilitate researchers in reproductive health to move the field from one of excellent science and excellent pragmatic trials to a precision medicine focused field, where women at high risk of complications can be given appropriate care and new effective interventions can be developed. Tommy's four centres of excellence include research teams from Edinburgh, Manchester, King College London, Imperial, Birmingham and Warwick who all have the ability to obtain detailed mechanistic information from tissue samples using techniques including sequencing of DNA, RNA in whole tissues, RNA sequencing in single cells, DNA methylation gene reads, and proteomics. Clinical phenotyping in-terms of past history and importantly future pregnancy, neonatal and infant outcomes is needed to facilitate translation of this scientific excellence to patient benefit.

Across the four Tommy's centres, a wide-ranging variety of samples are/will be collected including pre-conceptual endometrium, sperm, serum, plasma, serial samples in high and low risk pregnancy of plasma, serum, vaginal, dental microbiome, then at delivery adipose tissue, myometrium, placenta, membranes, cord blood, and after delivery neonatal brain. Currently these tissues are stored in six separate biobanks, all striving to achieve the same ideal situation. By combing these six into one virtual entity, it will allow us to ensure 1) quality and consistency of sampling and outcome ascertainment through unified SOPs for sample collection, 2) processing and tracking, 3) working with software engineers to link relevant clinical data and the development of a searchable database. The resulting biobank will have details of large numbers of women with diverse pregnancy problems, with high quality data collection and outcome follow up. This will ensure that samples are of maximum benefit to Tommy's researchers, as well as for others in the field and the wider research community.

This project focuses on building a National Biobank for Reproductive Health. The outcome will be a collection of tissues linked to other NHS databases containing pregnancy outcomes, subsequent pregnancy outcomes, neonatal and infant outcomes. This research topic is a key area relevant to MRC Strategic Aim 1: Theme Life course perspective. By delivering the project objectives, we will therefore make a significant contribution to MRC's strategic plan.

Wider Research Communities:
As well as benefitting researchers working in the Tommy's funded centres, the work will also have potential to impact in other research communities, specifically those interested in reproductive health and the developmental origins of adult disease. The samples linked to clinical meta-data will open new avenues of research for these groups.

General Public:
The work being done in this project is of direct interest to non-scientists, the project relates to overarching questions. These questions include "Why did my baby die?" "Why did I miscarry?" "Will this happen again?" The importance to the public is shown in the National Tommy's centre for miscarriage research that now enables 24,000 women per year to access treatment and support and participate in Tommy's research studies. Tommy's #misCOURAGE campaign continues to grow and resonate with women, attracting a UK and global audience. To date the campaign has reached over 16 million women on Facebook, with 7 million of them watching the campaign film; 7,000 taking part in a miscarriage survey and over 1,000 women bravely sharing their personal #misCOURAGE story.

Industry:
The planned project outcomes will make a significant contribution to our enhanced understanding of pregnancy complications. Since this topic is an important commercial biomedical research area, with considerable interest in new tests and therapies for the prediction, stratification and prevention of pregnancy complications. This biobank will be of direct interest to industries in this sector. More specifically, the project will provide one of the leading tissue banks in reproductive health worldwide and one of the objectives of this bid is to make these tissues and the associated metadata available to industry.

Medical Practitioners and Patients:
Although delivering the project aims is not expected to have an immediate impact on clinical practice, short term, it will facilitate the current Tommy's reproductive health research programme. Looking longer term (5-10 year horizon) the resource will facilitate a new personalized medicine revolution in the speciality. through the ability to aid the understanding of the mechanisms of pregnancy complications, the ascertainment of new biomarkers, and the development of new predictive tests Training and Skills:
The project will provide tissues for a large number (>100) of scientists, doctors, engineers, midwives, medical students, nurses to obtain research degrees (masters, MD, PhD) and develop their post-doctoral careers across all the Tommy's Centres and beyond. Thus this project will provide excellent training opportunities and will therefore positively impact the UK skills base. These skills will provide a positive impact first to the individuals in their future career and second to their future employers in either the industrial or academic sectors.

Tommy's Charity:
The establishment of the proposed Tommy's Biobank will be fundamental in adding value to the existing resources provided by Tommy's to their Centres of Excellence, and thus help to achieve their overall objective to help save babies lives.