Centromere Dynamics: Bridging Fundamental Mechanisms and Agricultural Innovation (360G-Wellcome-341968_Z_25_Z)

Cell division is fundamental to cellular life, requiring precision to produce healthy, viable daughter cells. Errors in this process can result in aneuploidy, developmental abnormalities, cancer, or cell death. Central to this process is the segregation of genetic material, mediated by a specialised protein complex at a chromosome locus called the centromere. Advances in long- read sequencing have enabled the complete assembly of centromeres, revealing that, despite conserved function, the DNA sequences vary widely in size and structure. Understanding how genetic and epigenetic factors shape centromere formation and dynamics is a critical question in biology and the focus of this proposal. This research leverages Arabidopsis thaliana functional genomics, live-cell imaging, quantitative proteomics, and long-read sequencing to investigate how centromere fidelity is regulated by the genome and chromatin environment. In Work Packages 1 and 2, we will identify genetic, protein, and chromatin factors contributing to centromere formation and fidelity. In Work Package 3, we will remodel centromeres to functionally influence chromosome inheritance, enabling applications in crop breeding. These insights will transform our understanding of this fundamental biological process, provide practical applications in crop breeding, which can be used to address global challenges in food supply, enhance food security, and promote human well- being.