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Axonal Microtubules Cut and Run

$720,000FY2009BIONSF

Drexel University, Philadelphia PA

Investigators

Abstract

The proposed research is important for understanding how nerves grow and branch. In particular, the project focuses on microtubules, which are elongated polymers that provide architecture for the nerve and also act as railways to move proteins and structures down the nerve. For the nerve to grow and branch, there must be mobility within the microtubule array itself. Notably, it has been discovered in recent years that only the shortest microtubules in the nerves are mobile. To generate more mobility within the microtubule array, nerves use special proteins that cut long microtubules into short ones. The purpose of this project is to study how these microtubule "cutters" work, and how they are controlled to get their job done properly. The cutting of microtubules is also important for many other types of cells, so the studies will be of interest and importance across various fields of biology. The general approach will be to make cultures of rat neurons, and then use reliable methods to alter the microtubule cutting proteins, and then see what the effects are on microtubules and the shape of the nerves. The results are expected to show what other molecules and mechanisms the neuron uses to control the cutting proteins so they cut microtubules at the right time and place in the nerves. Broad impact will be achieved through strong efforts to recruit minority students into the graduate program at Drexel University. Even broader impact will be achieved by an outreach to scientists and students in the developing nations of Africa. The Principal Investigator will work with African partners to develop strategies for bringing African students to the USA for part of their training so that the students can prosper, upon their return to their home countries.

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