Lynn, Nicole
Nicole is a graduate student in the Biochemistry, Molecular, and Structural Biology (BMSB) program. She received her Bachelor of Science in Biotechnology from California Polytechnic State University Pomona, with minors in Chemistry and Theater Arts. In the Fall of 2018, she came to UCLA and joined Dr. Jorge Torres’ laboratory. As an incoming student, she received the Cota Robles Fellowship in 2018. She entered the CMB training program in 2019.
Mentor: Dr. Jorge Torres
Regulation of intracellular microtubule dynamics plays an important role in the maintenance of cellular functions inherent to homeostasis, survival, and growth. During cell division, microtubules are rearranged, and the microtubule lattice is severed. This event is critical in promoting the appropriate microtubule density required in shaping the mitotic spindle formed at prophase, promotion of proper cellular architecture, motility, and division during interphase, and in bisecting the intercellular bridge microtubules during cytokinesis. Previous research has demonstrated a link between dysregulation of microtubule-severing enzymes and a myriad of developmental and proliferative disorders including gastrulation defects, ciliopathies, severe microlissencephaly, and cancer.
Katanins comprise a family of microtubule-severing enzymes who, during cell division, direct cleavage events through generating breaks at the microtubule polymer. Canonically, Katanins are composed of two subunits: a catalytic AAA ATPase containing p60 ‘A’ subunit and a regulatory p80 ‘B’ subunit. Unlike other mammals with shared homology, the human genome encodes for three Katanin A-subunits and two B-subunits, suggesting microtubule-severing and Katanins are more complex in higher organisms. In addition to this conundrum, human Katanins until recently have been poorly studied both functionally and structurally, and depletion of any one subunit has only shown mild defects in microtubule-severing.
The goal of my study is to characterize this family of human Katanins both structurally and biochemically. To better understand the roles Katanin isoforms play in vivo, I plan on using CRISPR/Cas9 based methods to generate stable cell lines with single and combinatorial knock outs of the A and B subunits; this will provide information on any possible compensatory mechanisms that occur between isoforms. Secondly, I aim to elucidate a full-length structure of the human B-subunit isoform (BL1), and its complexes with the A-subunit isoforms using Cryo-EM and X-ray techniques. These studies will increase our understanding of the human microtubule-severing machinery, and more broadly how their dysregulation can lead to human disease.
