Grant: Operating Grant

All life forms are assembled around a basic unit, the cell. Multicellular organisms have organized these unites into tissues and ultimately into even more complex structures like the human body. From beginning to end, all life depends on proper functioning of these single unit. Every human starts life as such a single cell, but during development, cells divide and differentiate to form specialized structures. To achieve this, different genes characteristic for the development of a specialized organ, such as the liver, must be activated. Misregulation of such gene activation programs can have severe consequences, causing developmental problems or serious diseases such as cancer. For instance, a tumor can be formed simply because a gene activation program is incorrectly executed within a single cell. Thus, to understand why such defects can occur and to be able to correct or prevent them, we have to understand how gene activation is achieved within a single cell. Yet paradoxically, to date most of what we understand about gene control has been achieved only by studying average behaviors of cells, not the individuals from which ha tissue develops or a rogue cell that madly divides to form a tumor. I have developed unique and powerful methods to study gene activation in single cells. These methods allow us to directly visualize how individual cells change their gene acitvation programs in real time, with a precision of seeing individual molecules being produced. Using these tools, I aim to determine what elements in the genome are responsible for precise control of normal gene expression within single cells and how, where and when such control breaks down.