Mechanisms of organelle transport in neurons

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Similar to a city, nerve cells, or neurons rely on efficient transport mechanisms for development and survival. Active intracellular transport allows neurons to ship membrane components that support cell growth, signaling molecules released from the cell, and trophic factors that are actively transported from outside the cell to support survival. Efficient transport is particularly import in neurons as the architecture of the highly polarized neuron is such that the tip of the axon can be quite a distant from the cell body where many of the cell's components are made. There are three primary facets to active transport: 1) Cellular cargo 2) Molecular motors 3) "Tracks" for movement. The goal of my research program is to understand the cellular and molecular basis for organelle transport in neurons with a particular focus on the motor proteins and cargoes involved in axonal transport. We approach this problem by directly imaging and characterizing active transport in living nerve cells. By studying dynamic events in living cells we are better able to analyze a biological process that is by its nature is dynamic. For example we are able to directly measure organelle transport and assess changes in transport parameters when we alter the activity of a motor protein responsible for carrying a particular cargo. We then complement our imaging work with biochemical methods to confirm motor-cargo interactions. My research program will ultimately yield answers to basic questions concerning organelle transport in neurons, however due to fundamental nature of transport to all cell types our findings will likely be relevant to other fields of cell biology. Furthermore, axonal transport disruption is suspected as an etiology in several neurodegenerative diseases such as Alzheimer's, Huntington's, and amyotrophic lateral sclerosis, that by understanding basic neuronal transport in healthy, these findings will ultimately help in understanding problems that occur in diseased neurons.