Selena Wong

Project

NLRP1-Mediated Host Defense and Pathogenesis in Corneal Epithelia

Inflammasomes are multiprotein complexes that function as intracellular sensors of pathogens. Upon pathogen detection, the inflammasome-sensor triggers a series of cleavage events which results in a lytic form of cell death called pyroptosis. In epithelia such as the lung and gut, NLRP1 is the predominant inflammasome-forming sensor. However, the role of NLRP1 in corneal epithelia is unknown. To characterize the role of inflammasomes in corneal epithelia, we used CRISPR-Cas9 to knock out genes required for NLRP1 inflammasome signaling in the human corneal epithelial cell line hTCEpi and treated them with Val-boroPro (VbP), a known activator of NLRP1. We found that VbP-induced inflammasome activation was dependent on NLRP1 and NLRP1-related signaling proteins. Our findings demonstrate that hTCEpi cells have a functional NLRP1 pathway, and suggest that the NLRP1 inflammasome mediates host defense and/or inflammatory pathogenesis in the corneal epithelium. We plan to test if pathogens that cause conjunctivitis elicit an NLRP1 response in corneal epithelial cells, which would implicate that NLRP1-mediated responses contribute to inflammation seen in conjunctivitis.

What I learned

I have learned to appreciate all the hard work and planning that goes into research. Prior to joining the Mitchell Lab, I had no prior exposure to research. Since then, I have gained a lot of knowledge about the scientific process and what it is like to perform research. Maintaining good communication with your mentor will make the project go smoother and make your research experience much more fun. Most importantly, this research experience has taught me that it is okay to make mistakes as it is part of the learning process.

Advice for future applicants

APPLY! There is no harm in applying. Plus, you get to practice your scientific writing and will get a better understanding of your project in doing so. It is also important to find a research topic that you are passionate about and find a mentor that fully supports you. Having a good relationship with your mentor is key as they will aid you in making progress in your project.

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