Researchers at the Francis Crick Institute and Queen Mary University of London have been awarded €9.8 million from the European Research Council to investigate how tissue homeostasis, the body’s ‘status quo’, is maintained over time, and how genetic mutations can help or hinder this process.
The pioneering six-year project, called MUTAHOME, is one of just 56 to be awarded funding in a competitive group of 548 applications from across Europe.
One of the most surprising biology discoveries of recent years is that genetic changes accumulate in adult tissues as we age. For most people, these mutations lie seemingly silent for years and only in a minority of cases they cause cancer. Scientists now hypothesise that these mutations may even contribute to the body’s ability to maintain tissue homeostasis.
Research leads Ilaria Malanchi, Dominique Bonnet, who are both based at the Crick, and Francesca Ciccarelli, who is based at the Crick and Queen Mary, are combining their complementary expertise in different areas of cancer research to explore the fine balance between advantage for the tissue and cancer initiation, and what can cause this balance to tip. Together they plan to create a detailed picture of how mutations affect the entire body.
Francesca Ciccarelli, Head of the Cancer Systems Biology Laboratory at the Crick, and Lead of the Centre for Cancer Genomics and Computational Biology at Barts Cancer Institute, Queen Mary, said:
“The idea for this project began with conversations between Ilaria and myself about why mutations accumulate in healthy stem cells over time. We asked Dominique to join the team after hearing her present evidence of the beneficiary roles of some mutations in blood stem cells. Winning this ERC grant is proof that new research is sparked from curiosity, and that these complex questions can only be addressed by combining diverse expertise.”
Ilaria specialises in how stem cells within solid tissues interact with their local environment; Francesca studies the evolutionary impact of genetic mutations in human tissues; and Dominique leads work on how the bone marrow microenvironment, including blood stem cells, changes as we age and in response to external insults like infection.
They will systematically study how stem cells change over time, accumulate mutations and interact with other cells locally. They will then use machine learning tools to identify if and when these mutations could be beneficial, and if there are biological signals linked to their advantage.
Dominique Bonnet, Head of the Haematopoietic Stem Cell Laboratory at the Crick, said: “An accumulation of mutations is nearly always seen as bad, but it could be conferring an advantage if it doesn’t lead to cancer. We’re hoping that this ambitious project will help us understand what environmental triggers are needed for mutations to become bad and cause disease.”
Head of the Haematopoietic Stem Cell Laboratory at the Crick
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