A research team led by James Briscoe at the Francis Crick Institute and David Rand at the University of Warwick have been awarded over £1.3 million from the Biotechnology and Biological Sciences Research Council (BBSRC) to establish a rulebook that defines the decision-making processes by which cells determine their fate or ‘type’.
Read more about James's lab at the Crick here.
How the body produces the right number of different cells during human development is a mysterious process. Researchers have made progress in understanding which chemical signals are responsible for some of these paths – known as cell fate decisions – but haven’t yet defined a set of rules that govern all decisions.
Working across the Crick and Warwick, James and David will develop a computer model that can identify universal features present in all cell fate decisions, including which genes are present and when.
The aim is to build a bigger picture view of early human development, where researchers can examine the moment cell fate is determined.
In their four-year project, James and David will first gather data using single-cell sequencing, which involves mapping the activity of key genes in a single cell.
Read more about David's lab at the University of Warwick here.
The researchers will then create the computer model based on this data, which will outline the rules governing cell fate decisions and make predictions about what a given cell will specialise into in a particular environment.
Finally, the team will test their new programme in a model of a vertebrate neural tube, a structure in the embryo that becomes the spinal cord. They will use the computer model to investigate how the embryo uses the combination, level and duration of chemical signals to generate appropriate proportions of each nerve cell type.
This work could be important for synthetic biology, helping to grow the right cell types for tissues used for medical or research purposes. It may also help researchers to understand developmental disorders of the spinal cord, which involve many different cell types.
James Briscoe, Group Leader of the Developmental Dynamics Laboratory at the Crick, said: “We're thrilled to receive this grant which brings together dynamical systems theory and cutting-edge molecular biology to tackle fundamental questions about cell fate decisions. My group has been working with David’s for a while and this project is a fantastic opportunity to deepen and continue our interdisciplinary collaboration. The ability to predict and direct cell differentiation would be transformative for designing engineered tissues and understanding disease processes."
David Rand, Professor of Mathematics at the University of Warwick, said, “Seeing how a supposedly abstract subject like mathematics can cast new light on a fundamental aspect of biology and medicine is particularly rewarding because it gives new ways of looking at such things and also feeds new ideas back into mathematics.”
