Grant: Operating Grant

Nearly every cell in our bodies contains our full genetic blueprint (DNA), but each cell uses only a small part of the blueprint to direct its function. For example, immune cells are specialized to fight infection and brain cells to process information. During development, cells receive instructions about which part of the blueprint (which genes) to use. They organize their genetic material so that parts that will be used are easy to access, while parts that aren't needed are stashed away. Thus different cells have the same genome organized in different ways. This genome organization is carried out by proteins that associate with DNA. Together, these proteins and the DNA form a structure called chromatin. Each time a cell divides, it duplicates the chromatin organization so that the same parts of the genome are used by the two new cells. We are studying how chromatin structure can be duplicated in one step in cell division called mitosis. Mitosis is the process that ensures that each new cell receives one full copy of the DNA. In mitosis, chromatin is reorganized so that each of the multiple long threads of DNA in cells (called chromosomes) condenses into a rod-like structure. These rods line up in the middle of the cell and are distributed evenly to opposite sides of the cell. Immediately after mitosis, the genome is reorganized to its cell type specific state. How cells remember the cell type specific chromatin organization is not understood and is the focus of our work. Polycomb proteins are special chromatin proteins that are important for remembering chromatin organization through mitosis. Failure to correctly duplicate chromatin structure contributes to many cancers and frequently results from malfunction of Polycomb proteins. We are studying Polycomb proteins in fruit fly cells to reveal the molecular processes they use to ensure cells remember how to organize and use their genomes. The same processes are likely to occur in human cells, and may eventually be