Institute researchers are part of a world-first research project that will unravel how human embryos develop in the first weeks and months after fertilisation, improving our understanding of fertility, birth defects and regenerative medicine.
The £10 million Wellcome-funded Human Developmental Biology Initiative (HDBI) will build a ‘family tree’ of how cells divide and specialise following fertilisation, to understand how tissues and organs develop and reveal new insights into how this process can go wrong. Professor Wolf Reik, Dr Gavin Kelsey and Dr Peter Rugg-Gunn, all group leaders in the Institute’s Epigenetics research programme, will contribute their expertise in studying early development utilising single-cell analysis and stem cells.
Around 3% of babies are born with developmental defects – problems that often start very early in pregnancy such as heart defects, spina bifida and cleft palate. But we know very little about why and how they happen.
The Initiative will create ‘family histories’ of cells from four particular time-points in development or organ systems – the early human embryo, the brain and spinal cord, the blood and immune system, and the heart and lungs.
For many years, developmental studies have relied on cellular and animal models. While this has provided important information, it’s also become clear that our understanding of early human development remains extremely limited.
To address this, the HDBI will tackle some of the biggest challenges that are holding the field back. Very few labs have access to human embryo tissue samples meaning that key pieces of research that will underpin the field have yet to be carried out. And when available, this tissue is incredibly diverse, reflecting the genetic and environmental origins, making insights hard to define.
By bringing the research community together, along with recent advances in embryo and organoid models, more sophisticated imaging techniques and genome editing mean that researchers can now gain unprecedented insights into human development. Analysis of cell-fate specification in the early embryo will use a parallel nucleosome, methylation and transcriptome sequencing method (scNMT-seq) pioneered in the Reik and Kelsey labs.
Professor Wolf Reik, Head of the Institute’s Epigenetics programme, commented: “The HDBI will support research into the earliest stages of human development by developing key experimental and computational methods. From a biological perspective, we are excited to understand early cell fate decisions at the epigenome level and to explore events which may prepare the embryo for gastrulation.
“From the technology perspective we are keen to apply our advanced single cell multi-omics sequencing methods to human embryos at different stages, thus contributing to this community-driven effort to understand human development better.”
Dr Peter Rugg-Gunn, group leader of a team studying human stem cells and the establishment of cell identity, added: “Our research over the last few years has uncovered new ways in which gene activity is controlled as human stem cells specialise towards particular tissues. The HDBI provides a tremendous opportunity for us to discover how these control mechanisms work directly in human embryos so that we can learn how these tissues are formed during development and why this process sometimes goes wrong.
“In turn, this information will help us to improve our stem cell models so that we can produce more accurate cell types for applications in regenerative biology.”
The project will involve donated human embryos and human foetal tissue. The UK has a strong regulatory and legal framework and the HDBI will work within and respect these regulations. The Initiative will actively work to consider the ethical issues raised by this growing area of research and includes a specific ethics programme and public engagement programme.
Andrew Chisholm, head of cellular and developmental science at Wellcome, said: “This new initiative brings together a diverse group of biologists from across the country to share their expertise and work together to build a ‘family tree’ of how different cells and tissues come together to form organs. This will create a treasure trove of data and technologies that will be made available to the community.
“Thanks to new techniques and technologies to study human development the HDBI will provide insights that could help our understanding of developmental disorders.”
The Human Development Biology Initiative is a five-year programme which involves researchers from UCL, the Francis Crick Institute, the Babraham Institute, University of Oxford, the University of Cambridge, the University of Dundee and the University of Newcastle. In addition, it will partner closely with the MRC-Wellcome Human Developmental Biology Resource.
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Institute news: New technique offers insights into early life 22 February 2018
About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.
About the MRC-Wellcome Human Developmental Biology Resource
The HDBR is a resource that allows researchers access to human embryonic and foetal material ranging from four to 22 weeks of development. It is organised from two sites: the Institute of Genetic Medicine, Newcastle, and the Institute of Child Health, London.
Wellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a politically and financially independent foundation.
25 July 2019