ABSTRACT

In this project the brewer''s yeast Saccharomyces cerevisae is employed to study the dynamic inner workings of animal cells. Animal cells are characterized by their numerous membrane-enclosed organelles, which serve to isolate various metabolic processes from one another. Each of these organelles must grow and divide within the cell. Little is known about the coordination of these processes. During various environmental conditions such as starvation, some organelles increase their numbers while others decrease in number. This project will provide insight into how the cell organizes and regulates the growth and shrinkage of organelle membranes. The PI has discovered a fascinating situation where two different organelles, the nucleus and the vacuole, form Velcro-like nucleus-vacuole (NV) junctions. The nucleus contains the genetic information and is considered essential. The vacuole is the digestive center of the cell and is filled with enzymes that degrade cellular constituents. During starvation, nonessential cellular components are delivered to the vacuole where they are degraded and recycled by a family of processes called autophagy (self-eating). Since the entire nucleus cannot be degraded, yeast evolved a way to pinch-off and degrade small nonessential pieces of the nucleus. This process, called Piecemeal Microautophagy of the Nucleus (PMN) takes place at NV junctions. Many other organelles come into close physical contact with each other, but NV junctions are the only one for which the junction proteins are known. During PMN, the nuclear membranes within the NV junction grow and expand. Other aims of this project include studying how the NV junction serves as a platform for assembling specialized membrane sub-domains with multiple physiological roles. Besides providing mechanistic insight into basic cell phenomena, the broader impact of this project includes developing state-of-the-art microscopy methods. The project also serves as a training ground for undergraduate and graduate-level researchers, and is used in both lecture and laboratory courses at the University of Rochester. The work is done in consultation and collaboration with scientists around the world, including colleagues in Canada, England, Germany, Austria, and Australia. Finally, this project will yield insights into how cell processes have changed over evolutionary history, providing a wonderful opportunity to bridge the otherwise distinct fields of evolutionary biology and molecular cell biology.

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