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.  

Experts at Newcastle University have a leading role in the project, including studying the family tree of blood and immune cells to establish their origin, and to apply genome editing to examine the biological processes during early development.

Refining treatment approaches

Professor Muzlifah Haniffa, from Newcastle University’s Faculty of Medical Sciences, said: “Our examination of blood and immune cells will have implications for stem cell therapy and regenerative medicine and improve our understanding of childhood cancers such as leukaemia.

“Furthermore, some of our immune cells, such as macrophages, seeded early during development and persist to adulthood are involved in inflammation and disease. Understanding their family tree will help us develop new treatment approaches.

“HDBI research will complement the Human Development Cell Atlas studies pioneered at Newcastle University in collaboration with Wellcome Sanger Institute.”

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 scientists know very little about why and how they happen.

The new research initiative will create ‘family histories’ of cells from 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.

Unlike Newcastle, 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.

Professor Mary Herbert, from Newcastle University’s Faculty of Medical Sciences, said: “In collaboration with researchers at the Crick Institute, my team and I aim to apply novel approaches to enable us to study fundamental biological processes in living human embryos. 

“This innovative research will, for the first time, provide an in vivo system for investigating key aspects of the very earliest stages of human development, up to the time of implantation.

“Our work has the potential to greatly advance our understanding of the causes of infertility, chromosomal abnormalities and inheritance of mitochondrial DNA.”

Insight into human development

By bringing the research community together, along with recent advances in embryo and stem cells models, more sophisticated imaging techniques and genome editing mean that researchers can now gain an unprecedented insight into human development.

Professor Rick Livesey, based at UCL and one of the researchers leading the HDBI, said: “We know surprisingly very little about how humans develop. By understanding what is ‘normal’ in development we will be able to see how things can go wrong, offering new avenues for research.

“In addition, the insights from this work could help regenerative medicine reach its full potential.”  

The project will involve donated human embryos and human fetal 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 Newcastle University, UCL, the Francis Crick Institute, the Babraham Institute, University of Oxford, the University of Cambridge and the University of Dundee. In addition, it will partner closely with the MRC-Wellcome Human Developmental Biology Resource.