Clayton Caswell's laboratory at the Virginia-Maryland College of Veterinary Medicine has secured three prestigious National Institutes of Health R21 grants, each spearheaded by a graduate student.

"Discoveries are made by young people or young people in the field. They come in, and they're not burdened by what we think we know," said Caswell, associate professor of bacteriology at the veterinary college.  

Securing the three grants not only highlights the innovative research at the veterinary college but also underlines Virginia Tech's Global Distinction initiative, aiming to enhance institutional excellence across the education, research, and outreach missions. By empowering student researchers, Caswell's lab demonstrates the veterinary college's commitment to fostering the next generation of scientific leaders while advancing crucial fields such as microbiology and infectious disease research.

Three grants, three students

The three National Institutes of Health grants highlight the diverse and impactful research conducted in Caswell's lab.

  • Defining the atypical quorum sensing system of Brucella spp, led by Mitch Caudill. Most bacteria use a system called "quorum sensing" to communicate when many of them are together. Brucella is unusual because it uses this system even when only a few bacteria exist. Caswell's lab wants to understand how Brucella's unique quorum sensing system works. Researchers also want to find out how Brucella makes its communication signal. Most bacteria use a known method to make these signals, but Brucella does it differently. Project number 1R21AI180524.

  • Elucidating the regulatory mechanism of a Brucella-specific small RNA required for virulence, led by Kellie King. Brucella has a small regulatory RNA called MavR. MavR works by telling MurF, an enzyme involved in helping build the bacteria's cell wall, to slow down. The research team thinks that by slowing down this wall-building process, Brucella may become better at hiding from the body's defenses and surviving inside the cells it invades. The goal is to understand precisely how MavR works and why it is crucial for Brucella to cause illness. Project number 1R21AI182899.

  • Characterizing a novel Brucella small RNA critical for cell envelope integrity, led by Tristan Stoyanof. This grant examines another small RNA (Bsr7) that appears essential for the bacteria's ability to withstand membrane stress, a critical factor in its survival within host cells. In this study, researchers want to understand how Bsr7 works and its importance. They think that without Bsr7, Brucella might not be able to survive well inside the body or cause illness as effectively. Project number 1R21AI183022.

All three grants focus on understanding unique aspects of Brucella bacteria that contribute to its virulence and survival within host cells. They explore different regulatory mechanisms - quorum sensing and small RNAs - that play crucial roles in Brucella's pathogenicity. These studies aim to identify potential targets for new therapeutic strategies and vaccine development against Brucella infections.

Over 2.1 million new human cases are reported worldwide each year

With over 2.1 million new human cases of brucellosis reported worldwide each year, these studies are highly relevant to animal and human health. Brucella infections also affect various domestic and wild animals, causing reproductive issues such as abortions and sterility. This directly impacts pet owners and livestock farmers. Veterinarians deal with Brucella infections in animals and play a crucial role in preventing transmission to humans.

While less common in the United States, this disease remains a significant health concern in many parts of the world. Additionally, Brucella's potential as a biological weapon makes this research important for public health and biosecurity. 

A student-driven approach to research

"Without the students, none of these grants are possible," Caswell said. "They're the ones that are really the conceptual drivers behind it."

This student-driven approach to research is a cornerstone of Caswell's mentorship philosophy. 

Drawing from his own experiences with influential mentors, he strives to create an environment where students can take ownership of their projects and develop as scientists. 

"Every student is different, every training is different," Caswell said. "I have to tailor it. You have to learn what people respond to."

The path to these successes was not always smooth. "We've done a mountain of work that doesn't go anywhere," Caswell said. "That can be really tough, especially for a graduate student." However, it's this resilience in the face of setbacks that makes the eventual breakthroughs more rewarding.

Brucellosis research

It was during his postdoctoral work at East Carolina University that Caswell first encountered Brucella, the pathogen that would become the focus of his career to date, and a researcher who became a mentor. This mentor, Marty Roop, had connections with the veterinary college through a former dean, Gerhardt Schurig. 

Caswell's path to the veterinary college was influenced by the institution's history in brucellosis research and its excellent facilities. "We work at a higher containment level - BSL-3," Caswell said. "Not everybody has a BSL-3 facility, and we have a really great one here." 

Caswell, who had worked in medical school settings, was attracted to the chance to work with animal biology experts at a veterinary school. Virginia Tech's interdisciplinary environment has proven fertile ground for innovative research and collaboration.  

Fulfillment in teaching and service

"I love the teaching that I get to do. I love the service that I get to do," said Caswell, who views those roles as integral parts of his work at Virginia Tech.  

Caswell speaks warmly of the collegial atmosphere within the university, the veterinary college, and among international collaborators. This spirit of cooperation enhances the quality of research and provides valuable opportunities for students to network and gain exposure to different perspectives.

Reflecting on the nature of scientific discovery and what keeps researchers motivated despite the challenges, Caswell said: "I can probably count on one hand the really exciting moments where something, I don't want to call it discovery, but where you're like, 'Wow, this is super exciting.' But those moments do happen. It's very fulfilling, it's very exciting, and that's what keeps you going."

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