Controlling the Dynamics of a Model Filamentous Biopolymer

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This award by the Biomaterials program in the Division of Materials Research is cofunded by the Cellular Processes program (BIO/MCB). The goal of this research project is to understand how stabilizing and destabilizing factors can tune the dynamics of a model biopolymer. Regulation of the microtubule network is essential to the process of intracellular organization. Microtubule-associated proteins and enzymes control the length and dynamics of single microtubule activity, and thus the network. This project will examine destabilizing enzymes from the microtubule severing enzyme family that is an important group of regulators that can cut microtubules anywhere along the length and cause depolymerization. Additionally, the ability of microtubule stabilizers, such as MAP4 and tau, and their ability to stabilize microtubules alone and to antagonize the activity of severing enzymes also will be studied. Using multi-color total internal reflection fluorescence imaging system, microtubules performing dynamic instability in the presence of fluorescently-labeled accessory proteins will be studied. With this project, both graduate and undergraduate students will be trained at the interface of life sciences and physical sciences. This interdisciplinary training would be very important to prepare them for future industrial and academic careers. The PI has established a strong track record in successfully recruiting and educating students from diverse backgrounds. Recruiting and training of under-represented minority students will be the focus of the planned outreach activities.The goal of these fundamental scientific studies is to understand how the cell controls the length, growth, and shrinkage of microtubules. Microtubules are filaments found in almost all cells. They support the structure of the cell, and their arrangement into a cell-wide network that is important to organize the inside of cells. In order to understand how microtubules organize the inside of the cell, one must understand how the length, growth, and shrinkage of microtubules themselves are controlled. Experiments will be performed where individual microtubules one-at-a-time will be observed in the presence of other proteins using a specialized microscope. These other proteins could either cut microtubules or protect them. This project is to understand the exact mechanism of tuning on the destructive and constructive proteins that regulate the length, growth, and shrinkage of microtubule. This research will use multi-color single-microtubule imaging by fluorescence microscopy to examine the dynamics of microtubule activity. As part of teaching and training, graduate and undergraduates students will be trained in biological physics at the interface between the physical sciences and life sciences. Biological physics is an important interdisciplinary field that is needed in many industrial and academic careers. As part of this project, underrepresented students will be recruited and trained in the research activities of the investigator.