Higher animals and plants are made up of a multitude of cells, all of which are specialized to carry out particular functions. Each cell must be organized properly; for instance, proteins must be located in the correct part of the cell. Mislocalization of proteins in cells can have myriad consequences, including development of cancer and other diseases. One method animals and plants use to direct proteins to specific places in the cell is the attachment of a fat (lipid) molecule, which changes the chemical properties of the protein and often leads to the association of this protein to the periphery (outer rim) of the cell. This project aims to increase our understanding of the processes by which proteins become modified by lipids, and how this modification affects the function and localization of these proteins. These studies have potential implications for treatment of cancer, Hutchinson-Gilford progeria, Hermansky-Pudlak syndrome, and choroideremia in humans, and conferring drought tolerance and disease resistance in plants. Plants are used as a model for these studies, due to the survivability of plants with major defects in lipid modifications and their ease of use in the laboratory. This project includes participation by, and training for, members of groups that are underrepresented in science, who were successfully recruited in outreach efforts across the country. This project also forms the basis of curriculum development for local high school science courses and will be integrated into a display at the Saint Louis Science Center for educational outreach.
Life begins with genes, tiny regions of DNA we inherit from our parents and that help determine what we (and all other forms of life) turn out to be. But knowing all the genes of an organism isn’t enough; we need to know where and when those genes are expressed, what proteins they make, and, finally and perhaps most importantly, how those proteins behave in the cell: what they do, where they are, what they make, all contributing to what each cell, and ultimately what each organism, looks like. Protein behavior is governed by post-translational modifications—chemical modifications that regulate the behavior, activity, and location of proteins, contributing to the dynamic activities of cells. One type of post-translational modification is the addition of fats to proteins. These additions tell the protein where to be in the cell; often, it means moving the cell to the cell membrane, the outside layer of the cell that is also made of fat (fats are attracted to each other like drops of grease in a frying pan). Once there, these proteins can, among other things, send and receive signals from outside of the cell, helping to govern the behavior of the cell. In humans, such proteins can cause diseases, including cancer, if they are mislocalized or overactive. In plants, such proteins govern a series of processes ranging from control of stem cell activity to responses to and tolerance of drought and other adverse conditions. This study helped to increase our understanding of how proteins get modified by fats, and included the discovery of a new components responsible for these modifications and their role in basic plant processes such as growth, development, and the allocation of stored chemical energy which may have implications for biofuel production.
