MRC Wellcome Trust Human Developmental Biology Resource (HDBR)
Lead Research Organisation:
Wellcome Trust
Department Name: UNLISTED
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.
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.
-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.
People |
ORCID iD |
Publications
Spiers H
(2017)
5-hydroxymethylcytosine is highly dynamic across human fetal brain development.
in BMC genomics
New S
(2015)
A matter of identity - Phenotype and differentiation potential of human somatic stem cells
in Stem Cell Research
Thomas MG
(2014)
Abnormal retinal development associated with FRMD7 mutations.
in Human molecular genetics
Halim D
(2016)
ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.
in Human molecular genetics
Clowry GJ
(2015)
An enhanced role and expanded developmental origins for gamma-aminobutyric acidergic interneurons in the human cerebral cortex.
in Journal of anatomy
Webb EA
(2013)
ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies.
in Brain : a journal of neurology
Mould AW
(2015)
Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation.
in PLoS genetics
Alves DB
(2017)
BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.
in Brazilian oral research
Mason JO
(2016)
Building brains in a dish: Prospects for growing cerebral organoids from stem cells.
in Neuroscience
| 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 |
| 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 |
| 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 | Barts Health NHS Trust partnership |
| Organisation | Barts Health NHS Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Academic collaboration with Barts NHS. |
| Collaborator Contribution | Collection of fetal tissues from Barts NHS for storage and distribution for research by the HDBR biobank. |
| Impact | Many embryonic and fetal HDBR samples have originated through this collaboration. |
| Start Year | 2011 |
| 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 | 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 |
| Description | HDBR website, ongoing |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | HDBR's website which provides information on the fetal biobank, its purpose and its operation, including details of research outputs. |
| Year(s) Of Engagement Activity | 2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019,2020,2021,2022,2023 |
| URL | http://www.hdbr.org |
| 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 |