The behaviour of a cell is defined by the set of genes it expresses and by its commitment to either a quiescent or a proliferating state. These processes are regulated by a family of enzymes called the cyclin-dependent protein kinases (CDKs). Our group studies CDKs that control both cell division and gene expression. We adopt a structure-based approach to understand how CDKs work, how they in turn are regulated, and how their inappropriate activity can contribute to the development of disease. We are using chemical fragment mapping to identify protein-protein interaction (PPI) sites that distinguish CDK-cyclin modules to identify separation of function mutants and as starting points for chemical probe discovery. We have recently incorporated AI approaches and are designing small proteins that specifically target cyclin PPIs as an alternative route to probing CDK biology. Our vision is to determine how individual PPIs specify CDK-cyclin function and develop tools that selectively disrupt them, simultaneously dissecting mechanism and identifying new therapeutic approaches.