Defining the cellular architecture: intrinsic regulation of organelle size, shape and number

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The eukaryotic cell maintains its architecture despite the continuous flow (or trafficking) of membrane through the secretory and endocytic systems. Organelle maturation underlies trafficking in the endocytic system, and requires membrane fusion, fission and invagination events. These processes must be balanced to maintain organelle size, shape and number; properties that define the architecture of the cell and permit proper organelle function and inheritance. Although it is unclear how this balance is achieved, we know that mechanisms in play are intrinsic to the system. Furthermore lumenal volume is important for this balance, as changes in volume trigger Rab GTPase signaling, which in turn controls organelle morphology. Unlike cellular volume however, the mechanisms that control organelle volume are poorly understood. The aim of this proposal is to identify and characterize mechanisms that control organelle volume and regulate Rab signaling to maintain organelle size, shape and number. To achieve this goal, I will perform quantitative assays of organelle fusion, fission and invagination in tandem with lumenal volume and ion measurements using S. cerevisiae and its vacuole as models. This work will represent a major breakthrough in the field of cell biology, and has global significance to our basic understanding of intracellular trafficking and how the eukaryotic cell architecture is defined and maintained.