As antibiotic resistance makes everyday infections tougher to treat and emerging pathogens drive challenging infectious-disease outbreaks, researchers in Kansas from multiple disciplines and institutions are teaming up to target pathogens and overcome antibiotic resistance.
The National Institutes of Health recently awarded the University of Kansas $5.8 million for Phase 3 of KU's Chemical Biology of Infectious Disease center, an NIH Center of Biomedical Research Excellence (COBRE) that was established in 2016. The center recruits, mentors and supports investigators across KU, KU Medical Center, Kansas State, Wichita State and other regional partners as they address urgent challenges in infectious disease and antibiotic resistance using chemical-biology approaches. A Phase 3 award is intended to help a research center along a sustainable path beyond COBRE support at the federal level.
P. Scott Hefty, professor and chair of molecular biosciences at KU, is the center's director and principal investigator. He is joined by co-principal investigators Jon Tunge, professor of medicinal chemistry, and Mark Farrell, associate professor of medicinal chemistry.
The primary reason for establishing the CBID center was to bring together infectious disease biologists - and we're really good at identifying gene products and factors that contribute to disease - and bridging that expertise with our colleagues in chemistry, medicinal chemistry, pharmaceutical chemistry and bioengineering. They're excellent at developing chemical tools and probes and approaches to address those infectious disease components. Oftentimes, expertise isn't shared. We're both good at what we do, but together is where we really do excel."
P. Scott Hefty, professor and chair of molecular biosciences at KU
The center gives investigators access to four core research labs organized around infectious disease high-throughput screening, computational chemical biology and molecular modeling, synthetic chemical biology and flow cytometry. Participating researchers can apply for funds for pilot projects and vouchers for "low-barrier" use of the center's core facilities. The center also brings together researchers for monthly programs and annual symposia.
"You just have to get scientists in a room, sharing science, talking science, and great things come out of that," Hefty said. "Often, collaborations and events happen organically."
For proof of that under Phase 1 and 2 funding, the center can point to seven faculty recruited, contributions to 15 startups, about $25 million in NIH funding over 10 years and $90 million from broader research projects, pilot projects and cores; authorship in more than 600 publications and 80 scientific affiliates.
Beyond research, Hefty said the center has contributed to faculty development and retention as well as high-tech regional workforce development.
"There's a lot of training that goes into this, and it cannot be understated the number of undergraduates, graduate students and postdocs that have had an opportunity for 10 years and will for at least another five, to learn these techniques, tools and approaches," he said. "They're going to go out, whether it's in Kansas regionally, into new professions. That workforce development, the training that happens for our students, I think that is one of the primary outcomes."
Beyond developing pathogen-specific compounds and tools, Hefty said the theme of fighting antibiotic resistance would guide research under the center's Phase 3 award. Rather than developing broad-spectrum antibiotics, research will pursue more targeted treatments to protect the body's beneficial microbiome while defeating resistance mechanisms.
"We know antibiotic resistance has run rampant, and we need better tools and approaches to treat this," said the KU researcher. "One of the things that we're really interested in is, can we develop chemical tools, probes and approaches that just target the pathogen of interest? So, if we have an infection with staph, strep, enterococcus, can we target those organisms without disrupting the rest of the flora that's in our bodies? And can we develop tools to address the antibiotic resistance mechanisms that currently exist?
"I would deem that an incredibly positive outcome if in 10 years there's an established, formal research chemical biology center with all those scientists that we recruited and supported still participating within those activities," Hefty said. "It could continue to focus on infectious disease or expand into other areas - that could be cancer, that could be Alzheimer's or neurological disorders - but that there's an established research center that continues to support the group of investigators at KU, KU Med and other institutions."
Hefty acknowledged the KU Office of Research, the College of Liberal Arts & Sciences and the Kansas Board of Regents for their support of the center. The School of Pharmacy also has been a key partner, he said, along with researchers at KU Medical Center in microbiology and biochemistry.
The center's collaborative approach will be on display Oct. 16-17, when researchers and other stakeholders gather for the fifth annual Chemical Biology Symposium. The event is expected to draw more than 100 attendees, with regional participation including K-State and Wichita State.
According to organizers, "The symposium seeks to provide a forum for Graduate Training in Chemical Biology trainees and Chemical Biology of Infectious Disease researchers to present their work in chemical biology and to cover special topics with invited speakers."
For Hefty, this kind of cross-pollination of ideas among institutions, departments and disciplines is the whole point.
"We're breaking down a lot of those disciplinary walls and barriers so that interdisciplinary science can occur and happen in a very productive way," he said.
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