Research

Our lab is interested in understanding how large-scale cytoskeletal networks generate and respond to forces inside of cells, and to figure out how these mechanics contribute to the success of key cellular processes. We are particularly interested in how microtubule networks are organized and maintained during processes such as cell division and neuron growth. We are fascinated in understanding how nanometer-sized proteins work cooperatively to produce micron-scale cellular behaviors. And though decades of research has identified a majority of the biological 'parts' that are involved, we still do not understand the mechanical rules that dictate how all of these pieces work together to accomplish goals like the reliable segregatation of DNA into two new daughter cells or the establishment and maintenance of axons and dendrites in neurons.

Microtubule bundles crosslinked by PRC1 being disrupted by kinesin motors

The Forth lab is currently working to understand how the cell builds the complex machinery needed to divide. We are particularly interested in understanding how ensembles of proteins, which are each only several nanometers big, cooperate to build structures that are thousands of times their size (microns), and to understand how forces and motions within the cell are regulated. We have recently been very interested in a non-motor protein, called PRC1, that crosslinks microtubules to form higher-order bundles. We have shown that PRC1 generates viscous resistive forces that (1) increase as microtubule filaments slide faster and (2) increase with a higher concentration of PRC1 crosslinks. We have also demonstrated that PRC1 can form clusters under tension that further stabilize the microtubule bundles and clarify how stable anaphase central spindles are built. We have also recently collaborated with the Al-Bassam lab at UC Davis to show that the tail domain of Eg5 is required for efficient generation of microtubule sliding forces, a finding that has implications for bipolar spindle assmebly in mammalian cells.

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