Similar to the human body as a whole, cells, the building blocks of organisms, have a nonhomogeneous composition, where the different components--nucleic acids, proteins, and lipids--segregate to different parts of the cell to perform different functions. In neurons, such vital functions include the formation of stable connections, called synapses, which constitute the basis of cognition, including memory formation. To maintain proper function of the synapse, a large number of proteins and ribonucleic acids are transported from their site of synthesis in the cell body to the remote synapse. This project proposes to reinvestigate the mechanism of this transport, aiming to test the idea that many of the components needed at the synapse are transported together, rather than individually. This process would be analogous to carrying many passengers in a canoe along a river, instead of letting each of them swim in the water. State-of-the-art technologies will be used to visualize, with live imaging microscopy, the simultaneous transport of individual proteins within neurons and to purify and identify, with modern techniques of biochemistry, the components of the molecular machinery that powers this transport. These studies are expected to provide evidence for an alternate form of transport of synaptic components, thus challenging the current view of transport within neurons. Novel tools for the study of intracellular transport will be generated and made freely available to the research community. The study will be conducted with a research team that includes high school and Master's degree students, and will thus contribute to the education of future generations of scientists. The results will be largely disseminated via publications, meeting presentations, and inclusion in course lectures. The successful completion of this work will constitute a major step forward in understanding how brains develop and function at the cellular and molecular level.
