Integrating Phosphatidylcholine Metabolism with Cell Growth Regulation

The human body is made up of approximately ten trillion individual cells. Each cell is surrounded by a membrane that isolates the cell from surrounding cells and its external environment. Inside each cell are more membranes that further divide the cell into individual compartments that perform specific functions (eg. duplicating genes, making energy, or getting rid of unwanted or used up cellular garbage). Think of the cell membrane as the outside of a ball and each compartment as smaller balls inside the larger one. As a cell grows and divides to make another cell the membranes of the cell also have to be duplicated. How cells membrane duplication is coordinated with the signals inside a cell that result in cell growth are poorly understood. The research proposed in this grant application aims to determine what cellular signals coordinate cell growth with the generation of cell membranes so that cell growth and membrane synthesis are properly synchronized. A specific aspect of this grant that relates to human disease is based on a recent finding that an inherited disease that causes chronic pain and partial paralysis is due to a mutation in the NTE1 gene. My lab was one of the first to determine that the function of the NTE1 gene is in the regulation of membrane balance. We are now trying to understand how a defect in the NTE1 gene causes this disease. Very little is known about how NTE1 works as we only recently determined its function. To try to understand how defects in the NTE1 gene result in chronic pain and paralysis we will use high throughput robots to screen for genes and drugs make cells either sicker or healthier when the NTE1 gene is not functioning properly. We aim to learn more about what aspects of cell biology NTE1 regulates that cause pain and paralysis. This research will also act as the first step in the identification of drugs that could be used to treat this devastating inherited disease.