KU scientists win grant to help infectious disease fight

LAWRENCE, Kan. — The rise of antibiotic-resistant diseases is frightening to contemplate, but a team of University of Kansas researchers has won an $11 million grant it hopes will help to find a solution.

The five-year grant from the National Institutes of Health will enable researchers on KU’s Lawrence campus to better contribute to the fight against infectious disease by studying fundamental biology with the use of small molecule chemical probes.

NIH funding will create a Center of Biomedical Research Excellence (COBRE): Chemical Biology of Infectious Disease. The grant was awarded to Thomas Prisinzano, professor and chair of the Department of Medicinal Chemistry. He is joined by Scott Hefty, associate professor in molecular biosciences.

“Our center is focused on developing chemical probes and strategies to better understand and treat infectious diseases. These efforts are especially significant with the rampant rise of antibiotic-resistant bacteria and the absent treatments for many emerging infectious diseases,” Prisinzano said.

The grant will bring together researchers from KU, KU Medical Center and Kansas State University. The grant places an emphasis on developing promising infectious disease research efforts of junior faculty members, Prisinzano said. In addition, the new center will establish three core facilities that can be utilized by researchers at KU and other universities:

• An Infectious Disease Assay Development Core will provide expertise, facilities, services and training in the area of HTS assay design, development, validation, small- and large-scale screening for organism (i.e., cell)-based or biochemical infectious disease targets. Assay development and performing high-throughput screening for infectious disease targets can be very similar to other biological and disease targets; however, there are often specific biological hazards associated with infectious disease targets that can require special consideration and conditions.
• A Computational Chemical Biology Core will provide comprehensive computational support, including chemical virtual screening, physical property prediction, target validation, hit identification, lead optimization, pharmacophore identification and pharmacokinetic and dynamic modeling. In addition, the core will provide information management infrastructure supporting the creation and management of scientific data analysis workflows, project reporting and database management for chemicals, including their structures and biological properties.
• The Medicinal Chemistry Core will provide synthetic chemistry support, including the validation of hit compounds obtained through high-throughput screening, quality control and analysis of compounds, synthesis of compounds unavailable commercially but needed by researchers, structure–activity relationship studies based on HTS campaigns and optimization of fragment binders. Although most libraries used for screening and fragment efforts will continue to be commercially procured, the MC Core will continue ongoing efforts to create novel libraries for screening and fragment work.

While the grant to Prisinzano is for five years, it can be renewed for additional years. The Higuchi Biosciences Center at KU also hosts two other NIH-funded COBRE centers, both of which were renewed. The Center for Molecular Analysis of Disease Pathways, led by Susan Lunte, Department of Chemistry, is in its fifth year, and the Center in Protein Structure and Function, led by Robert Hanzlik, Department of Medicinal Chemistry, is in its 13th year.