Matilde Galli and Juan Garaycoechea awarded with ERC Starting Grant

Galli and Garaycoechea each receive up to 1.5 million euros to finance their research for a period of 5 years. The summaries of their project proposals are stated below.

Galli: “Timing cell cycles in multicellular development”

How do cells time their divisions during development to ensure that our organs have the proper architecture and shape? Understanding how cells determine their division pattern is key to understanding how cell divisions can become deregulated in diseases. Additionally, it will pave the way for tissue engineering research that is aimed at recapitulating specific cell division patterns for tissue and organ replacement.

The project will investigate the mechanisms by which cells change their cell division patterns during development in two species of roundworms, also called nematodes. These nematodes are powerful model organisms to study cell division due to their invariant division patterns. The research team will map changes in the activity of genes that occur as intestinal cells undergo different types of cell divisions. Furthermore, they will identify the molecules that drive cells to change their cell division programs. Finally, a new imaging platform will be implemented to visualize and manipulate intestinal cell divisions as they occur within the developing nematodes.

Garaycoechea: “Mechanisms of proliferation-independent mutation”

Cancer is caused by the accumulation of genetic changes. These alterations, known as mutations, are the consequence of mis-repaired DNA damage or misincorporation of nucleotides (i.e. the building blocks of DNA) during cell division. The textbook view is that cell division is a requisite for the introduction of mutations. However, very surprisingly, new sequencing studies have shown that non-dividing cells such as neurons also accumulate mutations over time. This indicates that mutations can arise without genome replication. Importantly, this type of mutations makes up the majority of mutations in human tissues, but their mechanism is completely unknown.

This ERC project will use a novel DNA single cell sequencing strategy to study mutations in single cells and mice, combined with genetic inactivation of candidate pathways to understand how these mutations come about. The team aims to answer two main questions: how do cells mutate without cell division (1) and what drives these mutations in tissues (2)? Together, the proposed work aims to shed light on the most common mutational process in human tissues.

About ERC Starting Grants

The ERC Starting Grants are designed to support excellent principal investigators at the point in their career at which they are starting their own independent research team or program.

397 early-career researchers have been awarded an ERC Starting Grant. Researchers affiliated with our partners at Utrecht University and UMC Utrecht have also received ERC starting grants.