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One of the central questions in cell biology is how proteins are sorted to particular regions of the cell. While most of the focus in cell biology has been on how different membrane bound compartments are defined, relatively little is known about how the cytoplasm is organized.  While the cytoplasm of the cell is often viewed as little more than a sea of enzymes, the complexity of the biochemical and signaling pathways within the cell argue that a high degree of organization is necessary to ensure that pathways are regulated correctly and don’t interfere with each other.  Our long-term goal is to identify and characterize these novel mechanisms of intracellular organization and their role in human disease.

In order to achieve this goal, we are using a systems biology approach to identify and characterize novel intracellular compartments.  This approach has uncovered 38 novel intracellular structures, including four intracellular filaments.  Since many of the enzymes that form these structures are in critical metabolic pathways, we are currently focused on how assembly of these structures is used as a novel mechanism to regulate metabolic activity within the cell.

In parallel with this effort, we are studying a different mechanism for organizing the cytoplasm – sorting information in the form of mRNA.  By transporting mRNA encoding a protein to a desired location, the synthesis of the protein can be spatially restricted to particular cytoplasmic regions.  Establishment of these domains is further enhanced by a translational control mechanism that ensures that only the properly targeted messages are translated.  This sorting mechanism has been implicated in processes as diverse as stem cell differentiation, regulating synaptic strength in neurons and embryonic pattern – underscoring the importance of understanding mRNA localization for medicine, neuroscience, and developmental biology. 

We are also studying how cells sort information in the form of mRNA to particular domains within the cell. This sorting mechanism has been implicated in processes as diverse as stem cell differentiation, regulating synaptic strength in neurons and embryonic patterning – underscoring the importance of understanding mRNA localization for medicine, neuroscience, and developmental biology.