Grant: Discovery Grants Program - Individual

Proteins are functional output of genes in a cell. In general, proteins regulate physiological functions of a cell. Depending on the physiological need of the cell, structure of proteins alters to render them active or inactive. Change in protein structure is called protein modification and various molecules attach to proteins to modify them. Addition of a fat (fatty acid) molecule to protein is one such protein modification that alters its localization and activation in a cell. These greasy proteins play important role in cellular function. Fatty acid addition to protein is catalyzed by acyltransferases. Proposed research project aims at understanding the role of one specific kind of acyltransferase called N-myristolatransferase (NMT) that attaches fat molecule (myristic acid, 14 carbon fatty acid) to important signaling proteins that regulate cellular differentiation and function. Proposed research is directed towards understanding the significance of fatty acid (myristic acid) modification of proteins during differentiation and function of neutrophils and T Lymphocytes which are important immune response cells in mammals. To study the role of NMT in neutrophil and T cells, embryonic stem cells (ES) will be used. Since ES cells can be induced to generate any kind of tissue and cells, they will be induced to generate neutrophils and T lymphocytes for the proposed study. Gene mutation or silencing is the best way of understanding gene function. Therefore, I will use NMT knockout (NMT gene silenced) ES cells to investigate the role of NMT in neutrophil and T cell differentiation and function. The outcome of the study would provide insight into cellular differentiation mechanism and would aid in designing strategies to correct any abnormalities in neutrophil and T lymphocyte functions.