Crick researchers awarded nearly £6m in Wellcome Discovery Awards

Crick researchers Caroline Hill and Xiaodong Zhang have been awarded nearly £6m in Wellcome Discovery Awards to study DNA repair and organ development in zebrafish and humans.

The grants will allow the scientists and their teams to answer key questions about how DNA is repaired and how cells are organised to different fates to form appropriately sized organs in the right place.

Xiaodong Zhang (left) and Caroline Hill (right)

Xiaodong Zhang and Caroline Hill

Understanding how DNA is repaired and inherited

Xiaodong Zhang, Professor at Imperial College London and seconded Group Leader of the DNA Processing Machines Laboratory at the Crick, has been awarded £3,400,000 to study DNA repair processes over the next eight years. Her project will focus on homologous recombination, which repairs breaks in DNA by exchanging similar genetic information, which has high similarity with meiotic recombination, which allows exchange of DNA to ensure that traits from both parents are passed to offspring.

A protein called RAD51 is involved in both cases, searching and pairing matching DNA sequences. Although lots of research has been done on RAD51, we don’t yet know exactly how it works, especially in coordination with other proteins and in the context of nucleosomes which the DNA is organised into.  

Xiaodong’s work will aim to understand the molecular mechanism of homologous recombination in the context of chromatin.

Xiaodong said, “I am really pleased, excited and grateful to the Wellcome Trust for this award. This will allow us to focus on unravelling the molecular mechanisms of DNA repair, which is the focus of my work at the Crick as a secondee, taking advantage of the leading expertise in DNA repair and chromosome biology, as well as state-of-the-art facilities. I also feel relieved as this award allows me to keep established expertise in the lab and enable us to focus on really challenging projects. I am grateful to people in my lab for their tireless efforts in establishing new protocol, new reagents and new systems that are now ready for us to pursue the proposed work.”

How cells become functional organs in the right place

Caroline Hill, Principal Group Leader of the Developmental Signalling Laboratory at the Crick, has been awarded £2,378,537 over six years to study how cells are specified to different fates in the embryo, to form appropriately sized organs in the right place and at the right time.

Caroline’s lab recently discovered that the cells that eventually become the internal organs in zebrafish embryos are induced in a random way. They found that early in development, a subset of cells in a particular region of the embryo switch to form the endoderm (to become internal organs) whilst those that don’t switch will form the mesoderm (to become other parts of the zebrafish like muscle and blood). The team now want to understand how this switch happens and what signals and molecules are involved. They will also determine how the numbers of these different cells are corrected later in development, and whether the same mechanism happens in humans.

Caroline said: “I was absolutely thrilled to receive this very substantial funding from the Wellcome Trust and very grateful. I’m really excited about this research and where it will lead. Massive thanks to my wonderful team past and present who have made the discoveries on which this grant is built. I also am deeply indebted to all my generous and patient colleagues who gave me excellent feedback on the proposal and helped me with multiple practice interviews. Also, a big thank you to the Grants team for all their help and support.” 

The Wellcome Discovery Awards provide funding for established researchers and teams from any discipline who want to pursue bold and creative research ideas to deliver significant shifts in understanding that could improve human life, health and wellbeing.

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