HPU Faculty Receive Nearly $412,000 from NIH

High Point University’s Drs. Heather Miller, associate professor of chemistry (left), and Meghan Blackledge, assistant professor of chemistry (right), received a nearly $412,000 Academic Research Enhancement Award from the National Institute of Health through its General Medical Sciences Institute.


HIGH POINT, N.C., Sept. 13, 2019 – High Point University faculty in the Wanek School of Natural Sciences have been awarded a nearly $412,000 Academic Research Enhancement Award from the National Institute of Health through its General Medical Sciences Institute. This is the first NIH grant awarded to HPU’s Department of Chemistry, and the first AREA grant awarded to HPU.

Drs. Heather Miller, associate professor of chemistry, and Meghan Blackledge, assistant professor of chemistry, will use the funding to continue to investigate the enzyme Stk1, a novel drug target in the bacteria, MRSA. The grant provides funding to support 11 undergraduate students to participate in research over the next three years. They will research how Stk1 functions promote antibiotic resistance and biofilm formation in MRSA.

“Essentially, our goal is to knock out the bacteria’s communication system so they don’t know they are being attacked by our existing antibiotics and can’t protect themselves,” says Blackledge. “This type of approach has the potential to rescue our existing arsenal of antibiotics so that they can be useful again.”

The NIH grant will allow Miller and Blackledge to develop these small molecules into more potent inhibitors and use those to expand their studies into Stk1. They hope to use their molecules to learn more about other proteins that Stk1 interacts with and find new pathways that it may control. This information will provide insight that can be integrated into novel therapies to treat MRSA infections and will provide a roadmap for studying similar enzymes in other medically relevant bacteria.

“We are thrilled to have been awarded these funds, which will support student research and facilitate acquisition of state-of-the-art research equipment for HPU’s Department of Chemistry and the new Wanek School of Natural Sciences,” says Miller. 

In addition to supporting Miller and Blackledge’s research, this particular grant is designed to continue to strengthen the research environment of the institution and expose undergraduate students to biomedical research. 

“We are very grateful to the NIH for this funding and are excited to continue our studies into Stk1,” says Blackledge. “None of this would have been possible without the hard work and dedication of our current and former undergraduate researchers. They generated incredible amounts of preliminary data to support this proposal and have been wonderful sources of inspiration and innovation. This award will allow us to work with even more students moving forward, further strengthening HPU’s incredible commitment to undergraduate research and experiential learning.”

More about Miller and Blackledge’s research:

Miller and Blackledge have been collaborating for several years studying small molecules that modulate bacterial behavior. They are particularly interested in identifying and synthesizing small molecules that reverse antibiotic resistance, which is a growing health concern in developed nations around the world. Their approach relies on finding antibiotic adjuvants, molecules that are not antibiotics by themselves but prevent the bacteria from defending themselves against existing antibiotics.

Making the enzymes and proteins that allow MRSA and other antibiotic-resistant bacteria to evade antibiotics takes a great amount of energy for the bacteria. Instead of producing these resistant enzymes and proteins constantly, the bacteria have evolved something similar to a missile defense system. Special proteins on the surface of the bacterial cell sense the presence of antibiotics and then send signals to turn on transcription of resistance genes. Ultimately, those genes lead to production of the enzymes and proteins that can destroy or elude the antibiotics and save the bacteria. 

Recently, Miller and Blackledge discovered several small molecules that were able to reverse antibiotic resistance in MRSA by inhibiting a particular enzyme called Stk1. Stk1 is a crucial player in MRSA’s antibiotic resistance pathways. It allows MRSA to sense the presence of antibiotics outside the cell and sends the initial signals that lead to transcription of resistance genes. By inhibiting Stk1 with their small molecules, Miller and Blackledge can make MRSA, which is resistant to common antibiotics such as penicillin, susceptible to these drugs again.

 

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