Mechanistic insights into the periodic control of transcription in the mammalian cell cycle

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All of us develop into complex human beings containing millions of cells from a single cell created by fertilization of an egg. To transit from this single cell state, cells must continually divide into two cells, and in doing so pass a copy of their genetic blueprint (ie their DNA) to the new cells. This process is generally referred to as cell division. It is therefore critically important to understand the fundamental mechanisms that control this process. Conversely, as we age, cells become incapable of division and become "senescent". This creates a problem as we can no longer generate new cells to replace old or damaged cells. Conversely, hyperactivation of cell division leads to cancer. Indeed, cancer is a disease caused by the malfunction of "normal cells" in your body, and one of these malfunctions involves the onset of cell division. If this process goes unchecked, large masses of cells develop which accumulate more damage, and ultimately give rise to tumours. Thus understanding this critical process of cell division in normal cells and ultimately how this goes wrong in cancers is vitally important. This project aims to understand how one key regulator, FOXM1, works to control cell division. The abundance of this regulator is increased in cancer cells but is decreased in ageing cells, placing it at the nexus of control of these two important processes. FOXM1 does not work alone but has partners which help it to decode specific subparts of the genome in a process known as transcription. Here, we will study known partners and identify new partners for FOXM1. We will investigate how they work together to control cell division. This will provide a platform for establishing whether the mechanisms we uncover are relevant in the context of ageing or cancer and might lead to the development of therapeutic strategies.