Target-based biosensor platform for discovering small molecules that modulate plant immunity and development
A yeast-based biosensor platform for high-throughput discovery of small molecules that target the LisH protein domain, a key regulatory element found in plant corepressors controlling immunity and development. Enables scalable screening across 64 LisH domain variants to identify species-specific bioactive compounds for agricultural and therapeutic applications.
Overview
This technology is a target-based biosensor platform designed to discover small molecules that modulate the activity of the LisH protein domain, a conserved regulatory element found in over 25,000 eukaryotic proteins. In plants, LisH domains are critical components of corepressors such as TPL, LEUNIG, and HOS15 that govern development and immune responses. The platform enables researchers and industry partners to identify previously unexplored small molecules capable of altering LisH domain activity, opening new avenues for crop protection, yield improvement, and therapeutic intervention.
The core value proposition is a scalable, high-throughput screening system that can uncover bioactive compounds specific to individual LisH domains across species, allowing precise modulation of transcriptional repression in plants and other organisms.
Technical specifications
Key features:
- A compact library of 64 yeast strains, each engineered to report on the bioactivity of a single LisH domain from a distinct species
- Scalable platform demonstrated in 1,536-well format for whole-genome interaction screens
- Successful proof-of-concept using Tegatrabetan, a known anticancer therapeutic that interacts with the human TBL1 LisH domain
- Synthetic biology reporter systems in Arabidopsis and tobacco for rapid validation of compound specificity and efficacy
- Compatible with standard chemical library screening workflows
The biosensor works by applying small molecules to yeast strains and measuring changes in transcriptional activity, enabling identification of both positive and negative regulators of LisH-mediated repression. Structure-activity relationship (SAR) analysis can be performed on related compounds to refine lead candidates.
Technology readiness level
The platform has been validated through the development and characterization of the 64-strain yeast library, with critical amino acids identified for transcriptional activity. Scalability has been demonstrated through a whole-genome interaction screen with the Arabidopsis TPL protein in 1,536-well format. A pilot screen using a known LisH-interacting compound confirmed the platform's ability to detect changes in activity, establishing feasibility as a drug discovery tool. Complementary reporter systems in Arabidopsis and tobacco are already developed for downstream validation of hits in plant systems.
About University of Washington
The University of Washington is a large public research university with campuses in Seattle, Bothell, and Tacoma, known for a broad portfolio from fundamental discovery to applied innovation. Industry partners engage through a South Lake Union research campus adjacent to a major life sciences district and through collaboration programs that place faculty and students alongside corporate R&D. The university’s integration with a major academic health system enables clinical translation and large-scale trials. Research is supported by competitive federal funding from NIH, NSF, DOE, and DoD. A dedicated technology transfer office manages IP, licensing, and startup incubation with prototyping resources.
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