MRI: Acquisition of Automated Isothermal Titration Calorimeter for Biophysical Research at Texas State University

Texas State University - San Marcos, San Marcos TX

Investigators

Abstract

An award is made to Texas State University to acquire an automated MicroCal PEAQ isothermal titration calorimeter for the analysis of interactions between biological macromolecules. Isothermal titration calorimetry (ITC) measures the heat generated by chemical reactions or processes. The relationships between heat and the fundamental thermodynamic parameters (free energy, enthalpy, entropy, and heat capacity) enables ITC to measure directly those properties that describe a system’s ability to perform work – a key concept for understanding biological life. Because of this, ITC is a classical method that is widely used to characterize the interactions between macromolecules, especially including nucleic acids and proteins. As the first calorimetric instrumentation for the analysis of biological macromolecules at Texas State University, the Automated PEAQ-ITC significantly expands the biophysical research capacity of the institution. Texas State University is a Hispanic-Serving Institution with a large population of first-generation and non-traditional students, and this ITC system provides invaluable training and education opportunities. The instrumentation will afford experience to undergraduate and graduate students in both biophysical methodology and contemporary high-throughput automation. In addition, this ITC will support ongoing efforts in research and education to integrate the disciplines of physics, chemistry, and biology for the precise and quantitative characterization of interactions between biological macromolecules that underpin all mechanisms of life. The Texas State Automated PEAQ-ITC will be used to analyze the energetics associated with a wide range of biomolecular interactions. In particular, we will use ITC to study protein-protein interactions that are part of protein-folding pathways, phase-separation events, cellular signaling pathways, and DNA repair complexes. Protein-nucleic acid interactions that drive the formation of complexes regulating DNA repair processes, mRNA trafficking, and protein translation will also be studied. Small molecule-DNA binding assays, monitored by ITC, will identify how the formation of noncanonical DNA structures (e.g., quadruplexes and triplexes) can be modulated by ligands. Finally, the automated feature of the ITC is especially beneficial for fragment-based ligand discovery and characterization, which will be used to find new reagents that allosterically control cell signaling networks. 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.