What we care about: Work in the lab is broadly focused on discovering and quantifying the molecular mechanisms that underlie microtubule dynamics and its regulation by accessory proteins. Our goal is to understand how properties of individual molecules give rise to the complex polymerization dynamics that emerge at different length and time scales from collective interactions among these molecules.
How we do it: We look for insights wherever we think we can get them. We use recombinant tubulin (yeast or human) to interrogate microtubule dynamics with biochemical specificity, and to unify results from disparate approaches. We use X-ray crystallography and cryo-electron microscopy to get structural information of tubulin, its assemblies, and its interactions with regulatory factors. We use quantitative biochemistry to understand the energetics of interactions and how site-directed mutations affect them. We use in vitro reconstitution and time-lapse microscopy (including single-molecule detection) to measure polymerization dynamics. We use computational modeling to test if our ideas have predictive power, yeast genetics to test for functional relevance, and more.
Some questions we are working on now:
+ how do TOG-domain-containing polymerases in the Stu2/XMAP215 family promote fast microtubule elongation?
+ what features dictate species-specific variation in microtubule polymerization dynamics?
+ what are the molecular events that lead to catastrophe, the abrupt switch from microtubule elongation to microtubule shrinking?
+ how does microtubule rescue work, and how do cellular factors promote it?
There are more questions we would like to be working on and more approaches we would like to be using.
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