The growth of organisms, and organs such as the brain, fingers and toes, occur by cells dividing and changing from simple precursors into complex cells with specific functions through a series of carefully regulated processes. The cell cycle controls cell division by requiring the cell to pass multiple checkpoints to ensure only a healthy cell can divide. Another important ability for a cell is to be able to stop dividing. For example, when no more cells are required in the developing brain, cells exit the cycle resulting in no more cells being produced than are needed. Failure to exit the cell cycle can lead to excessive cell numbers, and so-called overgrowth disorders, whereby organs are too big and often do not have the correct structure. In the brain this results in the disorder megalencephaly. While brains generally stop growing once fully developed, the brains of people with overgrowth disorders continue to grow. This growth persists even after surgical intervention, resulting in further complications. Taken together, these observations tell us that precise management of the cell cycle is required for development of the brain as well as other cells and organs in the body. The aim of my research is to investigate a family of 3 proteins called D-type Cyclins (CyclinD), that act as a molecular switch for the cell cycle. This will help to understand the molecular processes that control the cell cycle and how these lead to disease when they don't work correctly. When CCND levels are high, cells continue to divide to create more cells, however when CyclinD is switched off the cells stop dividing. I am interested in disorders that occur which CyclinD's do not get switched off, meaning cells continue to divide even when they're not supposed to. In particular, I want to learn more about the molecules that control this switch, what happens in a cell when the switch cannot be turned off and to develop molecules that target CyclinD in order to stop the cells dividing. Using this information, I hope to learn how cells signal to stop cell division normally and therefore how they coordinate the development of complex structures such as the brain. Currently there are no cures or therapies available that can specifically target CCND accumulation. Through my research, we have gained a better understanding of how CyclinD is regulated. Using this new knowledge, I have developed CyclinD-inhibitors that can overcome the effects of CyclinD accumulation and have generated relevant cell-based disease models in which to test them in. This study will therefore test a panel of CyclinD-inhibitors I have developed on a range of relevant disease models in order to test their therapeutic potential for cancers and overgrowth disorders.