# Ligand Discovery Project

> **NIH NIH P01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $428,489

## Abstract

PROJECT SUMMARY: LIGAND DISCOVERY PROJECT
The development of strategies, tools and infrastructure for the discovery of novel microbial metabolism
represents a major challenge to the post-genomic biological community. The functional properties of solute
binding proteins (SBPs) make them particularly amenable to large-scale functional annotation, as the first step
in a catabolic pathway is frequently the passage of a metabolite across the cellular membrane by SBP-
dependent transport machinery. The ability to identify the initial reactant (or a closely related molecule) for a
catabolic pathway provides an immediate toe-hold by placing significant constraints on the regions of chemical
space which need to be considered and, in conjunction with knowledge of colocalized and coregulated genes,
begins to define details of the in vivo biochemical transformations operating within the metabolic pathway.
Accordingly, a central goal of this project is to evaluate the wide-spread utility of targeting SBPs and related
proteins for initial functional insight. We have implemented a high-throughput differential scanning fluorimetry
(DSF) assay for the interrogation of ligands/metabolite libraries carefully constituted for specific subfamilies of
SBPs. In parallel, high resolution structural characterization of SBP-ligand complexes will reveal the
determinants responsible for ligand recognition, and delineate “specificity boundaries” required for confidently
defining the limits of annotation transfer.
The Ligand Discovery Project will specifically examine SBPs involved in carbohydrate and amino acid
metabolism and expand this strategy to include the ligand-responsive transcriptional regulators which combine
an SBP-like domain with a DNA-binding module. Finally, this strategy will be applied to the microbes that
compose the human gut microbiome. Combining experimentally defined SBP ligands and high resolution
structural information with genome neighborhood networks (Metabolism Project) and additional insights
gleaned from computational approaches (Modeling Project) results in a powerful multidisciplinary strategy for
the discovery of new metabolism. When systematically applied to the human gut microbiome, these
approaches will result in the discovery of new metabolic pathways important for communication between
members of the gut community, communication between the gut microbes and the human host, and in
particular will expand our understanding of the impact of microbial metabolism on human health and disease.
Most importantly, the strategies and tools described in this application will enable the discovery of novel
metabolism by the entire community.

## Key facts

- **NIH application ID:** 9918942
- **Project number:** 5P01GM118303-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** STEVEN C. ALMO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $428,489
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918942

## Citation

> US National Institutes of Health, RePORTER application 9918942, Ligand Discovery Project (5P01GM118303-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9918942. Licensed CC0.

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