MRC/Wellcome Human Developmental Biology Resource: a unique resource for studies of human embryo and fetal development

Lead Research Organisation: University College London
Department Name: Institute of Child Health

Abstract

Birth defects affect around 3% of pregnancies and, while pregnancy termination can be an option, very few childhood diseases of this type can be cured. The lives of children with birth defects are often dominated by the need for repeated operations, making heavy demands on families and the health service.

A priority for current research is to develop new treatments to correct birth defects. These might involve, for example, the identification of essential nutrients like folic acid, which is a current treatment for spina bifida.

Alternatively, stem cell transplants hold great promise for future treatments of many diseases. Birth defects arise when an essential gene fails to function normally during the construction of the body and organs of the embryo and fetus. This can be because of an inherited defect in the gene, or because of the presence of a drug or other damaging factor during pregnancy. An essential first step for research, therefore, is to determine precisely how genes function in the normal embryo, thereby providing information to guide the development of treatments for disease.

Studies in animals are valuable sources of information, but ultimately every gene should be studied directly in human embryos and fetuses before clinical treatments can be developed. The Human Developmental Biology Resource (HDBR) is the only service in the UK that enables studies of genes and their function directly in early human embryos and fetuses.

Staff of the HDBR have obtained ethics committee approval to collect embryos and fetuses from terminations of pregnancy, with the written consent of the mother. Samples are prepared for sophisticated gene studies, with some material being sent out to other laboratories with a registered project. To date, more than 1,320 samples have been collected by the HDBR and many hundreds have been provided to scientists. Moreover, 69 scientific papers have been published, describing new discoveries resulting from use of material in the HDBR. Advances in our understanding of cleft palate, dyslexia, and eye, kidney and liver defects have already resulted from these studies.

In this application, we are seeking five years funding to continue to develop the HDBR service. This will enable continuing studies of genes for human birth defects, as well as developing improved web-based methods for interacting with scientists to enhance the usefulness of the service, while keeping the public informed of the latest advances in this field.

Technical Summary

The MRC-Wellcome Human Developmental Biology Resource (HDBR; www.hdbr.org) collects, processes and provides human embryonic and early fetal material to the international research community, primarily for studies of human developmental gene expression. Sections on slides for in situ hybridisation (ISH) or immunohistochemistry (IHC), and fresh material for RNA or cell line generation, are provided free of charge. A customised in-house gene expression service, involving ISH and/or IHC on a partial cost-recovery basis, is offered to labs that lack gene expression expertise.

Over 1,320 embryo/early fetal samples have been collected, from 26 to 84 days post-conception. Organs up to 19 weeks gestation are available via the MRC Fetal Tissue Bank, now operated by the HDBR. Karyotype analysis is routine and, while most samples are normal chromosomally, the HDBR has collected examples of several aneuploidies (e.g. XO, trisomies) and structural abnormalities (e.g. neural tube and limb defects) that can be provided for research.

To date, 149 projects have been registered with the HDBR, of which 94 are in progress, mostly UK-based but with an increasing proportion from EU and USA. The current average is 3 genes studied per project. A total of 69 publications have incorporated data from HDBR projects, including papers in Nature Genet., Am. J. Hum. Genet., Hum. Mol. Genet., Brain and other high-ranking journals. A survey of users revealed a 90% level of satisfaction with the HDBR service. The service was considered unique and enabling of human developmental research that could not otherwise be undertaken.

High resolution gene expression data are stored in a publicly accessible database that currently contains data from 42 genes, with a further 30 genes in progress. The database allows gene searching, visualization of human expression patterns, and comparison to mouse, with extension to other species in future. Links to databases holding microarray or physiological data are under development.

The present application seeks a further five years MRC/Wellcome Trust funding to continue to develop the HDBR service. We will: (i) continue to provide high quality human embryonic/fetal material; (ii) extend cost-recovery for the in-house gene expression service to enhance value-for-money; (iii) investigate the future use of high throughput technologies for gene expression procedures, image analysis and data handling; (iv) exploit the sub-bank of abnormal embryos/fetuses for studies of pathogenesis; (v) extend web-based platforms for operating the HDBR and for interacting with users/the public; (vi) enhance awareness of the HDBR, to ensure maximal uptake of the service.

Publications

10 25 50

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Al-Jaberi N (2015) The early fetal development of human neocortical GABAergic interneurons. in Cerebral cortex (New York, N.Y. : 1991)

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Alfakir M (2012) The temporal and spatial expression patterns of ABCG2 in the developing human heart. in International journal of cardiology

 
Description Human Developmental Biology Resource (HDBR): an embryonic and fetal tissue bank for functional genetics and cell-based research
Amount £4,117,367 (GBP)
Funding ID MR/R006237/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2018 
End 01/2023
 
Description Human Developmental Biology Resource (HDBR): an embryonic and fetal tissue bank for functional genetics and cell-based research
Amount £4,117,367 (GBP)
Funding ID MR/R006237/1 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2018 
End 01/2023
 
Description Human Developmental Biology Resource: support for Human Cell Atlas
Amount £686,407 (GBP)
Funding ID MR/S036334/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 12/2020
 
Description Partnership Grant
Amount £4,117,367 (GBP)
Funding ID MR/R006237/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2018 
End 01/2023
 
Description Partnership Scheme
Amount £4,104,857 (GBP)
Funding ID MR/R006237/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2018 
End 01/2023
 
Description UK Human Developmental Biology Initiative
Amount £6,148,973 (GBP)
Funding ID 215116/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2019 
End 09/2024
 
Description WT/MRC Biomedical Resource HDBR Grant (2013-18)
Amount £1,437,162 (GBP)
Funding ID 099175 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2013 
End 02/2018
 
Description standard research call
Amount £1,526,179 (GBP)
Funding ID 082557/B/07/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2008 
End 02/2013
 
Description standard research call
Amount £1,353,481 (GBP)
Funding ID G0700089 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2008 
End 02/2013
 
Title HDBR human fetal tissue bank 
Description The Human Developmental Biology Resource (HDBR) is an MRC/Wellcome Trust funded human fetal tissue bank established to provide material to any project that is studying human embryonic and fetal gene expression in relation to congenital disease. In addition, gene expression studies are undertaken in-house by staff of the HDBR on behalf of workers who supply gene probes or antibodies. The HDBR provides expert advice on interpretation of gene expression patterns in relation to embryonic and fetal anatomy. 
Type Of Material Improvements to research infrastructure 
Year Produced 2008 
Provided To Others? Yes  
Impact Continuing increase in the number of gene discovery papers in which there are now human embryonic and fetal gene expression data, to establish the timing and tissue localisation of gene expression. Improved understanding of human fetal development as relevant to congenital disease 
URL http://www.hdbr.org
 
Title Human Developmental Biology Resource (HDBR) 
Description The HDBR is a fetal tissue bank that collects, stores and supplies human embryonic and fetal material for research. 
Type Of Material Biological samples 
Year Produced 2018 
Provided To Others? Yes  
Impact Research in human developmental biology has been enhanced by access to material from the HDBR. 
URL http://www.hdbr.org
 
Title HDBR sample and project database 
Description Database that contains all information about collected human fetal samples, their processing and usage, and details of registered HDBR projects that receive human fetal material for research. 
Type Of Material Database/Collection of data 
Year Produced 2012 
Provided To Others? No  
Impact Streamlining the HDBR operation on behalf of its users. Making the HDBR compliant with the requirements of the Human Tissue Authority. 
URL http://database.hdbr.org/Login.aspx?ReturnUrl=%2f
 
Description British Pregnancy Advisory Service (BPAS) 
Organisation British Pregnancy Advisory Service (BPAS)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Research projects that have benefited BPAS in its overall mission.
Collaborator Contribution Provision of fetal material for HDBR projects.
Impact Ongoing working relationship.
 
Description Collaboration with HDBR user groups, e.g. as below (but many other partners as well) 
Organisation Oxford University Hospitals NHS Foundation Trust
Department Clinical Genetics
Country United Kingdom 
Sector Hospitals 
PI Contribution The purpose of the HDBR is to provide human fetal material to a wide range of research laboratories in the UK and beyond, in order to enable studies of gene expression and related research in humans. To this end, a great many collaborations were established, with each laboratory being a registered user of the HDBR. Full details of these registered users were provided to the MRC as part of the successful application for follow-on funding in 2007 (G0700089), and are available upon request.
Collaborator Contribution The collaborating HDBR user groups brought research questions (usually newly identified human disease genes) for which human developmental gene expression data were obtained by HDBR staff.
Impact All publications in section 2 are the result of the collaborations with HDBR user groups.
 
Description HDBR newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Twice-yearly newsletter via email to all past and present registered users of the HDBR, to inform them of current activities and to encourage new project registrations.
Year(s) Of Engagement Activity 2016,2017,2018
 
Description HDBR web site 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Health professionals
Results and Impact Web site that gives details of the service provided by the HDBR and examples of outputs from previous projects

Increased demand for registration of projects with HDBR
Year(s) Of Engagement Activity 2008,2009,2010,2011,2012,2013,2014