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. Microtubule dynamics is a 'collective' behavior that results from interactions between many molecules. This is a cool kind of molecular problem! In essence, our goal is to determine how structural and biochemical properties of individual molecules dictate the complex polymerization dynamics that occur on different length and time scales. There are lots of ways to contribute to that.
How we do it: We are scrappy! We look for insights wherever we think we can get them. We are one of a handful of labs worldwide using recombinant tubulin to interrogate microtubule dynamics with mechanistic specificity; site-directed mutants also provide a way to unify results from disparate approaches that otherwise don't "talk to" each other very well. We use X-ray crystallography and cryo-electron microscopy to get structural information about 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 and to quantify biochemical properties of microtubule ends. 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 isotype- and/or species-specific variation influence microtubule behavior?
+ 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?
+ what are the pathways for, and biochemical determinants of, spontaneous microtubule assembly?
+ can we use genetic and/or evolutionary approaches to identify new classes of mutations to crack problems that have so far been intractable?
There are more questions we would like to be working on and more approaches we would like to be using. There is a lot of room to contribute, both to the lab and to the field more broadly.
If you might be interested, check out Join for how to get in touch.