OHIO professor Sumit Sharma awarded $450,000 grant from the National Science Foundation to lead collaborative study on proteins

Ohio University professor of Chemical and Biomolecular Engineering Sumit Sharma received a $450,000 grant from the National Science Foundation for a study he’s leading that will help identify small molecules that are able to inhibit protein-protein interactions.

These small molecules that Sharma and his team are researching will help in the treatment of diseases linked to the undesirable activity of interferon regular factors (IRF), like diabetes, inflammation, autoimmune diseases and cancer.

“I’m excited to receive this grant since there’s a great deal of satisfaction in receiving funding that allows you to continue to pursue your research goals,” Sharma said. “A lot of time and effort goes into writing research proposals, and so there is a sense of fulfilment upon getting funded.”

Sharma and his fellow research team comprised of Kelly McCall, professor in the Heritage College of Osteopathic Medicine, Steve Bergmeier, professor in the College of Arts and Sciences, and Doug Goetz, professor in the Russ College of Engineering, have been researching the nature of proteins, specifically to understand small molecule interactions, and how developing molecules that can control protein-protein interactions would impact numerous scientific disciplines including immunology, pathology, and cellular/molecular biology.

“We are specifically focusing on the dimerization of a family of proteins called the Interferon Regulatory Factors (IRF) that are involved in the immune response of the human body,” Sharma said. “To perform biological function, protein molecules in our body often dimerize or attach to each other and undesirable dimerization of proteins has often been linked to a variety of diseases. Understanding the processes involved in protein dimerization and their inhibition mechanism will also help us understand other protein systems as well.”

The research group uses computer-based modeling of biomolecular systems to study how two protein molecules bind to each other and how small molecules attach or bind to specific regions of proteins.

Using computational methods helps the team in rapid screening of the molecules and allows them to identify the “best” molecules that then can be synthesized and tested in labs to determine their efficiency in inhibiting protein dimerization.

"I feel very fortunate to be a part of this project with Sumit, Kelly and Steve,” Goetz said. “Sumit is a great leader and Kelly, Steve and I have been working together for a long time. What really makes this work exciting is the synergy of our group from computational science, to synthetic organic chemistry to basic cell biology. Hopefully our efforts will have a significant impact on biotechnology and perhaps lead to the development of novel molecular therapeutics."

Aside from the scientific and clinical impact of this study, the research team is aiming for this study to also advance biotechnology, including the manufacturing of specialty proteins and the ability to probe commercially important biological reaction mechanisms.

They plan to employ machine learning tools and molecular-scale simulation, coupled with experimental validation of the predicted molecular performance, to rationally design molecules that can control protein interactions.

“One feature of this project that makes it quite exciting is the interdisciplinary nature of the research,” Sharma added. “Our team is a collaboration across three colleges: the Russ College of Engineering and Technology, the Heritage College of Osteopathic Medicine and the College of Arts and Sciences, and it’s quite rewarding for each of us to learn from the other’s areas of expertise.”

Preliminary data for the project was generated by undergraduate student researchers supported by the PACE funds and by graduate students supported by the Biomedical Engineering (BME) program.

The researchers’ plans to advance science doesn’t stop with the study. They will also be involved in a number of outreach activities, including organizing district-level science fairs and participation in University-level programs such as the Program to Aid Career Exploration to advance the Appalachian region of Ohio through education.

The study is co-funded by Chemistry of Life Processes in the Division of Chemistry (Mathematical and Physical Sciences Directorate) and by the Process Systems, Reaction Engineering, and Molecular Thermodynamics Program of the Division of Chemical, Bioengineering, Environmental, and Transport Systems (Directorate for Engineering).