Oral Presentations and Performances: Session III
Characterizing Mincle-Ligand Interactions with Isothermal Titration Calorimetry (ITC)
Project Type
Presentation
Project Funding and Affiliations
2025 CBSD Phase III Pilot Award
Faculty Mentor’s Full Name
Asia Riel
Faculty Mentor’s Department
Department of Chemistry and Biochemistry
Abstract / Artist's Statement
The immune system is complex and essential for eliminating pathogens and mitigating tissue damage. Pattern recognition receptors (PRRs) are one of many proteins employed to initiate an immune response activated by pathogen- or damage-associated molecules. This project focuses on one such PRR, a C-type lectin receptor—Macrophage-Inducible C-type lectin receptor (Mincle). Over the past two decades, Mincle has been the target of small molecule design for activation and protection against specific bacterial and fungal infections such as Mycobacterium tuberculosis and Candida albicans. These pathogens are of prime concern for human health globally. Understanding the molecular components of how Mincle engages with ligands will enable development of improved immunomodulatory compounds. Despite this, understanding how and why small molecules bind and activate (or bind and fail to activate) Mincle remains largely unexplored. This project will explore the interaction between the carbohydrate recognition domain of the recombinant human Mincle protein and two different trehalose (carbohydrate) derivatives. The two trehalose derivative ligands have been tested previously for Mincle activation in vitro. One activated Mincle, but the other did not. We hypothesize that the active and inactive nature of the ligands is caused by differences in binding affinities and conformations. To investigate this hypothesis we will employ the gold standard biophysical technique, isothermal titration calorimetry (ITC). ITC will provide data such as binding affinity and heat of binding that will be instrumental in characterizing the nature of the Mincle-ligand interaction.
Category
Life Sciences
Characterizing Mincle-Ligand Interactions with Isothermal Titration Calorimetry (ITC)
UC 327
The immune system is complex and essential for eliminating pathogens and mitigating tissue damage. Pattern recognition receptors (PRRs) are one of many proteins employed to initiate an immune response activated by pathogen- or damage-associated molecules. This project focuses on one such PRR, a C-type lectin receptor—Macrophage-Inducible C-type lectin receptor (Mincle). Over the past two decades, Mincle has been the target of small molecule design for activation and protection against specific bacterial and fungal infections such as Mycobacterium tuberculosis and Candida albicans. These pathogens are of prime concern for human health globally. Understanding the molecular components of how Mincle engages with ligands will enable development of improved immunomodulatory compounds. Despite this, understanding how and why small molecules bind and activate (or bind and fail to activate) Mincle remains largely unexplored. This project will explore the interaction between the carbohydrate recognition domain of the recombinant human Mincle protein and two different trehalose (carbohydrate) derivatives. The two trehalose derivative ligands have been tested previously for Mincle activation in vitro. One activated Mincle, but the other did not. We hypothesize that the active and inactive nature of the ligands is caused by differences in binding affinities and conformations. To investigate this hypothesis we will employ the gold standard biophysical technique, isothermal titration calorimetry (ITC). ITC will provide data such as binding affinity and heat of binding that will be instrumental in characterizing the nature of the Mincle-ligand interaction.