“This instrument will help us to understand the thermodynamic underpinnings of what happens when two molecules bind together.”
Veronica Moorman and a team of faculty researchers from multiple disciplines across campus have been awarded a National Science Foundation Major Research Instrumentation (NSF-MRI) grant for $91,600 that will permit the acquisition of an isothermal titration calorimeter (ITC). The ITC will allow Moorman and her colleagues to obtain quantitative thermodynamic information about molecular interactions.
The award is Kettering’s seventh NSF-MRI award since 2012 which is the most of any higher education institution in the State of Michigan over that time.
"This instrument will help us to understand the thermodynamic underpinnings of what happens when two molecules bind together," Moorman said.
From a thermodynamics perspective, the energetics of molecular interactions consist of entropic (disorder) and enthalpic (heat released or absorbed) components which can be deconvoluted using an ITC. Moorman’s specific focus is the role of entropy in protein interactions. She hopes to connect changes in enzymatic activity over the course of evolution to entropic or enthalpic origins, a task that ITC will assist her in accomplishing with precision and accuracy.
Moorman, along with Jim Cohen, is currently using phylogenic analyses, including building evolutionary trees, to understand the evolutionary origins of YopH, a potent tyrosine phosphatase from Yersinia pestis, the bacterium that causes the bubonic plague.
Moorman intends to determine a likely ancestral protein sequence from the time of horizontal transfer using a method known as ancient gene resurrection. That sequence can then be expressed as a protein in E. coli cells, purified and analyzed using ITC and other techniques.
“We’re trying to understand how binding occurs with different targets and how different proteins will affect that binding,” Moorman said. “The idea is to understand how the protein evolved over time.”
In addition to Moorman’s project, the ITC will also be a vital instrument for the following ongoing projects across multiple disciplines on campus:
- Lihua Wang - Investigating the interactions of Ru(II) anticancer complexes with serum proteins
- Montserrat Rabago-Smith, Moorman and Wang - Understanding the role of catechins in cardiovascular diseases
- Michelle Ammerman - Identifying the RNA binding affinity and stoichiometry of the Trypanosoma brucei protein MRB6070
- Uma Ramabadran and Gillian Ryan - Quantifying the thermal effects of additives on phase transition materials
When it arrives in Fall 2015, the ITC will also be used in chemistry, biochemistry and applied biology laboratories to enhance student experiences in the classroom. The instrument may also be utilized as a teaching tool for future scientists participating in the Academically Interested Minds (AIM) and Lives Improve Through Engineering (LITE) pre-college programs on campus.