Groundbreaking NIH Grants Propel Shields’ Bacterial Pathogen Research at A-State

12/03/2024

Dr. Robert Shields (with dark shirt) and members of his lab team (from left) Karen Solano, a graduate student, and Emanuel Cazano, an undergraduate student, both in biological sciences, and Andrew Goode, a student at NYIT College of Osteopathic Medicine at A-State.

JONESBORO - Dr. Robert Shields, assistant professor of microbiology, and his research group at Arkansas State University recently received a grant from the National Institutes of Health (NIH) to continue their work. Only days later, they received another one, an unprecedented milestone in A-State's history.

With the new funding from the National Institute of Dental and Craniofacial Research (NIDCR), a division of NIH, Shields and his associates are investigating the oral pathogen "Streptococcus mutans," its genetic makeup, and mechanisms to combat its impact on the oral microbiome, a reference to the microorganisms, largely bacteria, that are always in the human mouth. These vary based on personal health, diet and oral hygience.

The two awards are federally categorized as an R01 - the second in A-State history - a $1.77 million award spanning five years, and an R15 totaling $419,161 over three years, putting the cumulative investment into these research projects in excess of $2 million. A-State announced Shields' R01 award in August.

"I am so proud of Dr. Rob Shields in successfully competing for these two awards. The NIH investment in his research program is a testament to the importance of the work on tooth decay bacteria," said, Dr. Travis Marsico, vice provost for research, innovation, and discovery. "Dr. Shields was the 2023 ABI New Investigator of the Year, announced at this year's annual symposium in September."

Noting that this is the first time A-State has ever had a researcher funded by the National Institutes of Health on two separate awards simultaneously, Marsico added, "Shields was also one of three invited faculty speakers at the Arkansas IDeA Network of Biomedical Research Excellence (AR INBRE) annual conference last month. His colleagues around the state are taking notice of his research team's contributions, and we are thrilled to have him representing A-State in these statewide venues."

Shields stated, "This research will allow us to develop new treatment modalities, both against S. mutans and other streptococcal pathogens."

An important aspect to the R15 project is the inclusion of undergraduate and graduate students and how the program enhances their academic careers to prepare them for the next step. The Shields Laboratory, located in the Laboratory Sciences East building at A-State, has provided exceptional research opportunities for graduate and undergraduate students.

"Undergraduate research experiences have many benefits for the students involved and there is clear evidence that mentees perform better in their careers after graduation," Shields continued. "This research is very accessible for pre-professional students and adds to their resume before applying to medical or dental programs. Andrew Goode, a first-year student in the doctor of osteopathic medicine program at the New York Institute of Technology-College of Osteopathic Medicine at A-State, completed his honors thesis in our lab, working on this project that is now funded."

Since joining the A-State faculty in 2021, Shields and his group have made key contributions to the understanding of genetic functions of S. mutans, its regulation mechanisms, and roles in oral disease.

"Providing students with authentic, basic and applied research experiences prepares them for the STEM workforce, and the Shields Laboratory is an A-State leader in this important professional preparation," Marsico added.

Dr. Robert (Drew) Fleming, assistant professor of mechanical engineering, is a collaborator on this award, reflecting the interdisciplinary nature of the work. Two ABI-affiliated researchers, from different colleges (Beck College of Sciences and Mathematics, and College of Engineering and Computer Science), are working together to make important discoveries.

"My contributions will be mechanical property measurements of dental enamel to evaluate changes in microstructure and surface demineralization in response to tooth decay," Fleming said. "This will be made possible with specialized instrumentation in my lab that was funded by a previous NSF Major Research Instrumentation grant, on which Rob Shields was a co-principal investigator. Without it, this kind of high-impact, interdisciplinary collaboration wouldn't be possible."

The NIH RePORTER is the agency's website that provides details about funded projects throughout the country. Users will see there are currently five NIH award recipients in Arkansas' First Congressional District, two of which are Shields' and all five of which are A-State or A-State-affiliated startup companies.

These details are in the abstracts associated with each project:

R01: Mechanisms of Integrative and Conjugative Elements in Oral Bacteria

Horizontal gene transfer through mobile genetic elements drives the adaptive evolution of bacterial pathogens and contributes significantly to the spread of pathogenic properties throughout bacterial communities. We recently discovered an integrative and conjugative element (a type of mobile element that is transferred from cell to cell via conjugation) on the genome of the oral pathogen Streptococcus mutans. In this project, we will investigate fundamental aspects of the element's biology and its influence on S. mutans pathogenesis, including the signals that govern this transfer, interactions with other mobile genetic elements and bacterial defense systems, and elemental mechanisms that may ultimately harm the host bacterial cell.

R15: Systematic Functional Genomics Analysis of the Oral Pathogen Streptococcus mutans

Tooth decay is very prevalent in the United States and a leading cause of the disease is the oral bacterium Streptococcus mutans. In this project we will construct a powerful new genetic tool, a sequence-defined transposon mutant library, that can be applied to identify genetic determinants of S. mutans pathogenicity. The results of this project could lead to the discovery of important genetic factors required for S. mutans to cause tooth decay, and lead to new approaches to control S. mutans infections.

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