CAREER: Organelle Networks Orient Cilia and First-Generation College Students for Success

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).

The goal of this project is to investigate the mechanisms that position cilia across the surface of cells. Cilia are evolutionarily ancient hair-like appendages that are critical for cell movement and sensation. Understanding how cilia are positioned is important because the position of cilia affects how both terrestrial and aquatic organisms acquire nutrients, sense their environment, and reproduce.

This research is based on the hypothesis that networks of interconnected organelles determine where cilia form, how cilia sense molecules, and how cilia move fluid. This research will be conducted by a team of primarily undergraduate student scientists, who will gain experience in cutting-edge fluorescence microscopy, image analysis, and genetic manipulation of evolutionarily divergent cells.

The scientific data generated through the proposal will be used to create an interdisciplinary mathematical modeling curriculum for teaching diffusion within cilia. Beyond teaching and scientific research, a major goal of this project is to form a longitudinal mentoring program for aspiring first-generation college students. During year 1 of the project, a cohort of 9th grade students will be assembled from a local low-income high school that qualifies for federal college preparation assistance (GEAR UP).

Throughout their high school career, this cohort will engage in cell biology research to understand how water pollution in a local river impacts cilia movement. Student scientific training will be complemented with family engagement, enrichment activities and college application assistance to increase the likelihood that these students enroll in STEM undergraduate programs at the completion of the project.

American Rescue Plan funding of this project supports this researcher at a critical stage in his career.

Cilia are microtubule-based structures that project from the surface of cells that span unicellular organisms, such as Tetrahymena, through multi-cellular organisms, such as humans. The molecular architecture of cilia is deeply conserved; in most organisms examined, cilia are composed of 9 radially symmetric doublet microtubules, called an axoneme, assembled on top of 9 radially symmetric triplet microtubules, called a basal body.

Despite the strong conservation of cilia molecular architecture, the physical location of cilia relative to the geometry of the cell is not conserved. This project utilizes evolutionarily divergent cells to test hypotheses for how membrane-bound organelles adjacent to basal bodies participate in the positioning, signaling, and bending properties of cilia.

The research will investigate interactions between membrane-bound organelles and basal bodies in both the unicellular protist Tetrahymena and cell cultures derived from mice and humans. This comparative approach aims to identify conserved mechanisms of cilia positioning using dynamic live-cell fluorescence microscopy, Förster Resonance Energy Transfer (FRET) quantified with Fluorescence Lifetime Imaging Microscopy (FLIM), ratiometric calcium microscopy, pharmacology, and genetic perturbations.

Overall, the results from this project will reveal fundamental mechanisms that impact how cells position cilia relative to cellular geometry. These results have implications for how cilia are organized to maximize cellular motility in aquatic environments and the transduction of signals from the extracellular space.

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.