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.
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.
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.
