MRC Wellcome Trust Human Developmental Biology Resource (HDBR)

Lead Research Organisation: The Wellcome Trust Ltd

Abstract

Birth defects occur in 3% of pregnancies and include conditions like spina bifida, heart defects and facial clefts, all of which pose serious medical problems for the child and family. While pregnancy termination can be an option, the ultimate goal is to learn how birth defects develop in the embryo, so that preventive measures can be offered. These might involve vital nutrients like folic acid, or stem cell transplants which hold great promise for future disease treatment.
The Human Developmental Biology Resource (HDBR) provides a unique range of services to collect/distribute human fetal material for genetic research. Most birth defects arise when an essential gene(s) fails to function in the early embryo, owing to an inherited defect or a damaging environmental factor in pregnancy. Using HDBR material, scientists are learning how critical genes contribute to human development and how mutations (mistakes) in these genes may lead to birth defects.Here, we seek funding to further develop the HDBR services; including an improved and expanded range of material offered for research, links with new national initiatives focusing on the genetic basis of human disease, and a priority of keeping the public informed of the latest advances in this field.

Technical Summary

The Human Developmental Biology Resource (HDBR; www.hdbr.org) is unique, being the only tissue-bank that provides the international scientific community with access to:
-High-quality materials from human embryonic and early fetal stages, including tissues for cell culture, RNAs from sub-organ specific regions and slides for spatial gene expression studies;
-An in-house gene expression service (IHGES) that undertakes studies for registered researchers;
-A unique web-based database for dissemination of human gene expression data spatially mapped to 3D models.
To develop HDBR activities, and extend them to meet new challenges and opportunities, our key objectives are:
-increase sample collection with a focus on intact specimens;
-expand the range of IHGES studies, to include studies of noncoding RNAs and alternative spliced products, and to develop techniques to maximize expression information obtained from rare human tissues;
-expand the range of materials provided, e.g. RNA, DNA and protein, from specific tissues to support sequencing, transcriptomics and proteomics projects;
-interact strategically with large-scale initiatives focusing on human development and disease.
By also improving our engagement with current and potential users, we will adapt the HDBR to meet the needs of functional gene characterisation, for the new genetics technologies.

Publications

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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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Bamforth SD (2013) Clarification of the identity of the mammalian fifth pharyngeal arch artery. in Clinical anatomy (New York, N.Y.)

 
Description Partnership Scheme
Amount £4,104,857 (GBP)
Funding ID MR/R006237/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2023
 
Title Human Developmental Studies Network (HuDSeN) atlas and human gene expression spatial database 
Description HuDSeN GXD is HDBR's spatial database, where gene expression data are mapped onto a series of 3-dimensional (3D) representative models. The database structure was cloned from EMAGE (http://www.emouseatlas.org/emage/home.php), modified for human, with continued support from the Edinburgh Mouse Atlas Project team at the MRC Human Genetics Unit. Synergies result from the direct search and comparison links between EMAGE and HuDSeN GXD. Since 2013 an additional 62 genes and nearly 300 entries have been added to the HuDSeN GXD. The HuDSeN atlas pages have expanded considerably since 2013 and now consist of 4 sections: 1) Carnegie stages: includes 3D models of embryos from CS12 to CS23 with annotated histology sections, defined anatomy domains and highlighted full sets of gene expression data; 2) Abnormal embryos: includes example movies of 3D models of embryos with sex chromosome aneuploidy and details of other 3D models available; 3) Fetal stages: has MRI models of the fetal brain at 10 and 13 PCW; 4) Organ systems: includes movies and sections defining pancreas, blood vessels, lower urogenital tract, neural tube domains and spinal ganglia at selected stages. 
Type Of Material Database/Collection of data 
Year Produced 2008 
Provided To Others? Yes  
Impact Gene expression data have been used in publications other than by the original contributing group. Overall these data contribute to the understanding of human embryonic and fetal development which is critical to investigating mechanisms of congenital and other human diseases with a developmental origin. A recent pilot study used two of the 3D models as templates for 3D printouts of the developing neural tube, as teaching aids in courses at Newcastle University and the University of Edinburgh. 
URL http://www.hudsen.org
 
Description Human Developmental Biology Resource (HDBR) 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution HDBR is a joint resource developed and run at two sites: Institute of Genetic Medicine, Newcastle University and Institute of Child Health, UCL. The partnership is with Prof Andrew Copp, Dr Dianne Gerrelli and the HDBR London staff at Institute of Child Health, UCL. HDBR Newcastle (Prof Susan Lindsay, Dr Steven Lisgo and HDBR Newcastle staff), together with HDBR London, collect human embryonic and fetal tissues and provide these to national and international researchers who have registered a project with HDBR. We also generate a range of materials (e.g. RNA, cDNA, DNA, protein, cells) from the tissues at researchers' request. At both sites gene expression experiments are carried out on behalf of registered researchers who request our in-house gene expression service (IHGES). In addition HDBR Newcastle established and maintains the HuDSeN atlas and human gene expression spatial database (HuDSeN GXD). All expression data from IHGES projects and from many in situ hybridisation and immunohistochemistry experiments carried out by registered researchers are made public in the HuDSeN GXD, the vast majority mapped to the appropriate 3D model which enables multiple genes to be compared in the same "embryonic space" and aids understanding of the anatomical location of the expression patterns.
Collaborator Contribution As stated in section above our partners in HDBR London, together with HDBR Newcastle, collect human embryonic and fetal tissues and provide these to national and international researchers who have registered a project with HDBR. We also generate a range of materials (eg RNA, cDNA, DNA, protein, cells) from the tissues at researchers' request. At both sites gene expression experiments are carried out on behalf of registered researchers who request our in-house gene expression service.
Impact Publications and entries to HuDSeN GXD
 
Description Genetics Matters day 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact The day consisted of presentations from researchers and also from patient or their family members. There were also hands-on activity tables. There was both an HDBR presentation and also three group members ran one of the activity tables. There was very positive feedback from the people attending and they requested that it be run again in 2016.
Year(s) Of Engagement Activity 2015
 
Description Genetics matters day 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This event followed on from the very successful Genetics Matters day held last year. This time there was increased participation from the members of the public following more varied advertising of the event. More time was given for hands-on activities, there were presentations by patients or their family members but there were fewer presentations by researchers. Again there was an HDBR presentation and group members led a hands-on activity table.
Year(s) Of Engagement Activity 2016
 
Description Meet the scientist event at the Body Worlds Exhibition, International Centre for Life 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact There were three parts to the activity- DVD showing stages of human embryonic development, microscope and slides with stained sections and computer-based 3D model with painted anatomical domains. The activity was situated near the "prenatal development" section of the Bodyworlds exhibition and provoked much discussion with the many children and adults who stopped to look and ask questions.

As activity took place in a science museum and was aimed at the general public, it is difficult to directly attribute impacts.
Year(s) Of Engagement Activity 2014
 
Description contribution to A-level student open day at Institute of Genetic Medicine, Newcastle University 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Group members prepared a hands-om session using a microscope and sets of slides. In the session they asked students to identify human from mouse sections and to explain why they thought these differences were important. Session led to many questions from students who were interested and involved in the activity.

Increased requests for work experience in my lab and request to contribute to a similar open day next year.
Year(s) Of Engagement Activity 2014