A researcher in chemistry at Florida State University will utilize new financial support to investigate methods to stop tuberculosis, recognized as one of the most lethal and contagious illnesses across the globe.
Yan-Yan Hu, a Professor of Chemistry and Biochemistry, will employ the five-year, $3.4 million grant from the National Institutes of Health to assist in discovering treatments that overcome tuberculosis resistance by studying the architecture and interactions of essential protein complexes in the mycobacteria responsible for tuberculosis and examining how these interactions affect cellular functions.
“We intend to investigate the interactions between proteins within functional complexes that are vital for cell division,” Hu stated. “The outcomes will assist in directing treatment strategies focused on these key interactions, thereby interrupting the cell division mechanism. Our findings will yield valuable insights for discovering innovative approaches to manage drug resistance.”
Mycobacterium tuberculosis, or Mtb, infects around 25% of the global population and stands as the foremost infectious disease killer, leading to 1.25 million deaths in 2024, as reported by the World Health Organization. Mtb frequently develops resistance to therapies since treating active tuberculosis necessitates a combination of antibiotics given at specific intervals over a six-month duration to eradicate the bacteria. When patients do not complete the entire treatment course, the bacteria learn to endure the therapy combination in subsequent treatments.
“Understanding this cell division is paramount because tuberculosis is becoming increasingly difficult to treat as mycobacteria continue to evolve and gain more drug resistance,” Hu remarked. “Many individuals also harbor what is termed dormant TB, or latent TB, where they hold the mycobacteria without manifesting symptoms or transmitting it to others until their immune system weakens due to aging or other illnesses. Between 5% and 10% of those with latent TB will progress to active TB during their lifetime.”
Hu and her team, backed by staff scientists and graduate scholars, will utilize the $2.2 million segment of the grant allocated to FSU to scrutinize a crucial collection of protein complexes driving cell division in Mtb: the QBL complex and the QZ interaction. The QBL complex links vital proteins in a cell’s cytoplasm to proteins located in another region of the cell known as the periplasm. The QZ interaction also anchors the Z-ring, a fundamental cytoskeletal element in bacterial cell division, to the inner membrane of the cell.
Membrane proteins of this nature possess segments of their structure on both sides of a membrane, which includes the exterior and interior of the cell. Their role is to facilitate the entry of nutrients into the cell or nucleus while enabling the expulsion of waste outside the cell. Additionally, they may communicate signals from the environment into the cell.
“Thus, these proteins are essential for cellular functionality; pharmaceuticals that attach to such proteins and inhibit their function can derail critical cellular activities, such as cell division,” explained Tim Cross, one of the principal investigators of the study and an emeritus professor of chemistry and biochemistry at FSU.
By modifying interactions and structures within these complexes, the researchers will study how these modifications influence the cell division process and identify changes that could render the process self-terminating.
Hu’s broader research agenda focuses on innovating and implementing novel solid-state nuclear magnetic resonance (NMR) techniques to examine various systems, ranging from biological entities like proteins to functional materials utilized in rechargeable batteries and fuel cells. NMR spectroscopy employs magnetic fields and radio-frequency pulses to investigate molecular structures and interactions at an atomic level, yielding insights into both the static configurations and dynamic processes of the bacteria’s proteins.
“Yan-Yan is an exceptionally unique researcher. She is a highly esteemed battery chemist now venturing into another area, which is both intriguing and bold,” Cross remarked. “Often, it requires a scholar with experiences spanning diverse fields to introduce new insights, methodologies, and concepts that merge to create remarkable advancements in research.”
This research, which encompasses biomolecular NMR techniques, computational biophysics, and cellular biology, is also supported by scientists from Harvard University, the University of Illinois Chicago, the University of Texas at Arlington, and the Nuclear Magnetic Resonance and Magnetic Resonance Imaging Facility affiliated with the National High Magnetic Field Laboratory located at FSU.
To discover more about the research conducted within the Department of Chemistry and Biochemistry, visit chem.fsu.edu. For additional details regarding research at the National High Magnetic Field Laboratory, go to nationalmaglab.org.
The article FSU chemist awarded $3.4M grant to investigate protein complexes in bacteria that cause tuberculosis initially appeared on Florida State University News.