Harnessing Comparative Genomics to Uncover the Principles of Somatic Evolution and Healthy Ageing (360G-Wellcome-349455_Z_26_Z)

Somatic mutations accumulate in our cells throughout life. A subset confer selective advantages that drive the expansion of mutant clones, contributing to cancer and a broad range of age-related diseases. While recent studies have revealed the ubiquity of these processes in human tissues, we lack a general framework for somatic evolution. Why do mutation rates, mutational processes and clonal dynamics vary across cell types and tissues, and which features matter most for preserving resilience as we age? This project pioneers a comparative genomics framework to address these foundational questions. The vast diversity of lifespans and physiologies across species provides a remarkable resource to interrogate the rules of genome maintenance. I will combine ultra-accurate sequencing with a uniquely curated cross-species tissue biobank to produce the first comparative atlas of somatic evolution. By studying somatic mutation and clonal dynamics across 30 species, including cancer-resistant elephants, long-lived whales, and ‘immortal’ invertebrates, I aspire to uncover the evolutionary principles that govern genomic maintenance in ageing tissues. This work will generate insights into the cellular processes that drive age-related decline, identify organisms with exceptional genome stability, and lay the groundwork for evolutionarily informed strategies to improve human healthspan, cancer prevention, and reproductive health.