Shaw Camphire Receives Glen de Vries Fellowship

Trillions of bacteria live in and on the human body. And while these bacterial roommates are often harmless or even beneficial, they can sometimes cause disease. Carnegie Mellon University’s Shaw Camphire is working to understand what makes good bacteria turn bad.

Camphire’s efforts have been recognized with the Glen de Vries Fellowship, which celebrates outstanding research achievement and potential among Ph.D. students in biological sciences. The fellowship is made possible by the generosity of the late MCS alumnus Glen de Vries.

Camphire, a fourth-year Ph.D. student in the Department of Biological Sciences, studies Streptococcus pneumoniae (often termed pneumococcus), bacteria commonly found in the upper respiratory tract of healthy people. But if the bacteria disseminate to other tissues, like the ears or lungs or blood, they can cause a problem.

“It’s really fascinating to me that these bacteria — which most frequently cause no symptoms or damage when colonizing us — can be misregulated and cause really severe harm,” Camphire said.

Pneumococcus exists in complex bacterial communities, where each individual bacterium produces and receives signals to sense the host environment and communicate with its neighbors. This ‘talking’ and ‘listening’ allow bacteria to modulate their gene expression in a coordinated manner to carry out tasks as a group.

Camphire is studying one of these communication systems, which involves the Rgg144 gene and the signaling molecule SHP144. Camphire’s advisor, Associate Professor of Biological Sciences N. Luisa Hiller and collaborators at the University of Leicester discovered that turning off the Rgg144/SHP144 system “had a really big impact on the bacteria's ability to make a mouse sick. So it seemed very important. But I kept wondering, what makes a bacteria ready and able to actually use it?” Camphire said.

“The bacteria encode Rgg and SHP in their genome, and we know it can be activated and it can do things — it’s linked to virulence behaviors like biofilm development and regulation of the cell capsule — but we don't know what's changing pneumo's ability to activate it or not,” he added.

Camphire uses molecular biology tools to investigate when and why a pneumococcal cell activates the system, including how and under what circumstances the Rgg144 gene turns on or off.

Camphire’s undergraduate degree is in biotechnology, and he enjoys applying molecular biology techniques to solve puzzles. After graduating from James Madison University, he spent three years working for a gene therapy drug production company, Vigene Biosciences, before joining Carnegie Mellon to pursue his Ph.D. After taking his first microbiology class, he realized that his interests and expertise in genes and how they are regulated could be applied to pressing problems in microbiology.

“Shaw’s strong molecular biology background has prepared him to examine cellular behaviors from the bottom up, building mechanisms from regulation of gene expression through to phenotypes,” Hiller said.

The Rgg144/SHP144 system captured Camphire’s attention for another reason — nearly all strains of pneumococcus and several closely related species use it to communicate. So, he wondered, could these different strains and species talk to each other?

He and Srujana Neelavar, a recent graduate of CMU’s Master of Science in Computational Biology program, looked at more than 7,500 different pneumococcus genomes and found that 97% encode Rgg/SHP. Further, a large majority of a close relative, Streptoccocus mitis, encode this system as well. Upon closer inspection, the differences may come down to changes in a few amino acids. The next step is to pair Rggs and SHPs across strains and species to determine which ones overlap. It's quite an undertaking.

“There are multiple steps of: Who talks to each other? Who doesn't talk to each other?” Camphire said. “What are the behavioral consequences when they do talk to each other? Does it signal for the bacteria to work together, or does it signal them to kill each other?”

Camphire, who Hiller praises for being “a natural collaborator with a genuine passion for discovery,” works on projects with collaborators in Carnegie Mellon’s Department of Biomedical Engineering and at The University of Leicester in the United Kingdom. He has presented his work at numerous conferences, including the Gordon Conference on Streptococcal Biology, where he was selected for the competitive oral presentations, and the Rustbelt Microbiome Conference.

He also has participated in programs at CMU’s Eberly Center for Teaching Excellence and Educational Innovation. He has taught a few sessions of Hiller’s graduate-level microbiology course — the class that first inspired him to pursue his current research path.

“The Hiller lab thinks about what the bacteria do and how that impacts the host. That brought me in a little more than I initially anticipated it would, but now I’m very into it, obviously,” Camphire joked.

“When I think about what my future research direction looks like in general, it’s how do microbes interact with people in both health and disease contexts and fascinatingly when it overlaps, like with pneumo,” he said.