NSF Postdoctoral Fellowship in Biology FY 2022: Defining the biochemical mechanisms of microtubule shrinking and nucleation by combining innovative experiments and simulations

Ammerman, Lauren, Dallas TX

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2022, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the fellow that will contribute to the area of Rules of Life in innovative ways. Most cells grow, remodel and divide using the cytoskeleton – a network of protein that function as a kind of scaffolding that gives shape and structure to the cell interior. A critical aspect of the cytoskeleton are small protein subunits called microtubules. Despite decades of study, many aspects of microtubule function and behavior are poorly understood. The Fellow will combine wet lab experiments with computational simulations to determine how new microtubules form, and how existing microtubules shrink (two behaviors critical for microtubule function). This award also supports the development of a local scientific outreach program. Microtubule shrinking and spontaneous assembly (‘nucleation’) rates ultimately derive from the structural and biochemical properties of αβ-tubulin subunits. It remains challenging to determine how interactions between subunits less than 10 nm long determine microtubule assembly dynamics on the μm scale. This uncertainty limits mechanistic understanding of how microtubule behavior can change between cells in the same organism, between different species, and even across taxa. To investigate how microtubules shrink, the Fellow will use pioneering measurements of mixed mutant-wild type microtubules complemented by kinetic Monte Carlo simulations. This hybrid computational-experimental approach will test hypotheses about mechanisms of microtubule dynamics in ways that were not previously possible. To understand how new microtubules form spontaneously, or ‘nucleate’, the Fellow will create new codes to simulate microtubule nucleation from unpolymerized αβ-tubulin. With these simulations, the Fellow will define the sequence of tubulin oligomers that leads to a new microtubule, and how the sequence depends on biochemical properties of αβ-tubulin. Training objectives include learning new skills in advanced microscopy, computational simulations and protein work. To broaden participation in science, the fellow will lead a microscope-based outreach program with a local middle school that serves a diverse student population. Lesson plans and materials will be made publicly available. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.