The surface of the cell (the plasma membrane) is the interface across which all communication between a cell and its external environment occurs. A wide range of proteins with different functions is found at the cell surface, and the presence of these proteins at that location tells cells how to respond to signals they encounter. A basic process called endocytosis selects and removes subsets of proteins from the surface, and thus controls how cells are able to respond to a multitude of instructions they receive from other cells. During endocytosis, a portion of the cell surface membrane is pulled into the inside of the cell in a small, spherical structure called an endocytic vesicle. Many different cellular components are needed to both decide which membrane proteins should be internalized, and to actually construct the endocytic vesicle. Work in the PI's lab and others has identified a large number of these components, in particular a component called clathrin and other components that work together with clathrin. These components are found in all eukaryotic cells, so this laboratory has been studying endocytosis using yeast cells, for which powerful molecular genetic tools are available. Interestingly, other eukaryotic cells can also use an alternate, clathrin-independent endocytic pathways, but it has been suggested that the clathrin pathway is the only endocytic pathway in yeast. However, the Wendland laboratory has identified a potential alternate endocytic pathway in yeast that does not depend upon clathrin, and has found some new components that are used instead of clathrin. The project focuses on how these new components enable yeast cells to make an endocytic vesicle.
Broader Impacts: The project proposed here will complement the Investigator's teaching and training mission in several important ways. (1) The undergraduate/graduate students who conduct these studies will learn critical thinking, planning, and presentation skills through writing reports and manuscripts, preparing lab meetings, and attending national annual scientific conferences. The lab has already been actively engaged in the training of underrepresented minorities, and is committed to future training opportunities. (2) The publication of results and the generation of tools and reagents will impact the broader scientific community. (3) The research activities will enhance our current knowledge for three courses; two graduate courses and one large-enrollment undergraduate Cell Biology course. (4) Contributions to the Integrated Imaging Center (IIC) have led to the acquisition of equipment that is used by the broader Baltimore, MD scientific community. (5) A six week module has been developed for a core Genetics Lab course in which undergraduate students conducted a synthetic lethal screen to both aid research under this program and to learn fundamental principles of genetics, while also being exposed to the excitement of performing actual scientific research.