Project 456357

he human body is exposed to a number of toxic insults on a daily basis. These insults can include both man-made toxins such as air pollutants and chemical pesticides as well as natural toxins that are constantly present in the environment such as ultraviolet light and heavy metals emitted from volcanoes. In order for humans to survive these insults, cells have developed a complex system to evaluate the damage and decide a suitable course of action. When the damage is minimal, there are simple mechanisms to fix the cell. However, when the damage is more extensive, the cell is faced with a key decision of whether to expend energy to correct the problem or to undergo a self-imposed death. This situation forces the cell to make a decision to activate one of two important cellular processes. The first process involves creating a surplus of energy to activate repair processes and is known as autophagy (self-eating). In autophagy, the cells recycle its non-crucial components and uses them to fix the damage. The second choice is to induce self-death, a process known as apoptosis. Although it would be more self-serving to use the energy to correct the problem, there is a point of no return where it is more deleterious to move forward due to increase chances of spreading problems to other cells. These problems could result in an increase chance of neurodegenerative diseases as well as various forms a cancer. One key component in the cell for making the decision between the two pathways is an organelle found in the nucleus known as PML nuclear bodies. The goal of our work is to understand how PML nuclear bodies protect cells and make the crucial decision between either repairing toxic insults or self-termination. Understanding how PML nuclear bodies function is important for understanding many diseases associated with aging and our work will provide us with important insights on how to deal with many diseases associated with aging.