Unlocking the Molecular Motors of Life: The Mechanics of AAA+ Proteins

At the heart of every living cell, microscopic molecular motors work tirelessly to maintain life. Among them, the AAA+ ATPase family plays a universal role: they convert chemical energy (ATP hydrolysis) into mechanical force to remodel specific cellular substrate. From activating gene transcription to degrading proteins or reshaping the cellular cytoskeleton, nature uses this single structural engine to drive incredibly versatile activities.

Our research aims to understand the conserved features of this molecular engine. Specifically, we want to decipher how the AAA+ core transmits its energy to various cellular targets, and why specific mutations within this core are increasingly linked to human diseases including cancer and neurodegenerative disorders.


Katanin: Model System to Study Cellular Remodeling

To decode these mechanisms, we are focusing on a critical cellular process: the severing of microtubules. Microtubules are dynamic polymers that form the cell’s structural skeleton, playing a central role in cell division, morphogenesis, and intracellular signaling.

While most regulatory proteins only act at the tips of microtubules, a unique class of enzymes—Fidgetin, Spastin, and Katanin—interacts directly with the microtubule lattice to sever it throughout its length, precisely controlling its size, density and organization. Despite their importance, how these enzymes physically sever microtubules and how they are regulated in space and time remains poorly understood.


Current Research Focus

Combining biochemistry, genetics, and live-cell imaging, we use the microtubule-severing enzyme Katanin in the model organism C. elegans to address three key questions: