By Kenna Bruner
Consider this: Bacteria that can feel their way to cells in order to latch on and cause disease. If that sounds like the plot of a horror movie, rest assured, these tiny one-cell organisms are not operating from conscious thought.
Developing and using optical tools to study new biology at high precisions with detailed precision is the focus of work conducted in the Joel Kralj Lab at CU Boulder, where researchers have shown that electrical activity occurs inside bacteria.
A new technology developed by Kralj is driving the field of bacterial electrophysiology in new directions and enabling researchers to study electrical activity in live bacteria.
“Bacteria have little electrical changes that send signals to alter their single-cell-organism bodies and do different things in their lives,” said Giancarlo Bruni, who is pursuing a PhD in molecular, cellular and developmental biology and is a research assistant in the lab.
“Every neuron in the human brain uses electrical potentials to communicate,” he said. “So, it was a surprising new discovery that bacteria had similar electrical potentials. No one had observed these in live bacteria until Joel developed the fluorescent voltage sensor.”
From these new discoveries, they want to answer such questions as: When bacteria infect people, how do those electrical signals change? How do antibiotics influence that electricity in bacteria, and can scientists harness that to find something to combat bad bacteria that are with us every day?
Finding a way to deter the electrical impulses that enable bacteria to detect cells could clear the way for scientists to develop new antibiotics.
Using lasers to excite proteins inside bacteria that fluoresce, Bruni monitors the fluorescence that is converted into signals from the bacteria. An example of a signal in humans is a growling stomach indicating hunger.
“Bacteria may have a different type of signal that tells them about their world,” Bruni said. “We had a recent paper published that suggests what we’re studying—electrical potentials—might be part of the pathway for sensing their mechanical environment or touching things, which is similar to how we feel the things we touch. We’d like to find a translational application for our research to take this very basic biology we’re studying and use it to help us find big, important translational cures for humanity.”
Being a scientist wasn’t Bruni’s first career choice. In fact, until he was a junior in college, he didn’t know science could be an actual career. Now, not only is he passionate about science, but he also is an advocate for research as a career choice for underrepresented students.
“I thought research was something medical doctors and professors did in their spare time,” Bruni said. “I didn’t realize it was a whole career path in and of itself.”
Once he was on the research path, Bruni found mentors who guided him in his career. This support inspired Bruni to pay it forward by serving as mentor to young students. He works with the CU SMART program, which places interested but underserved students in research labs at CU. He also shares his story with students in the Colorado Advantage Program when they come to campus to preview doctoral programs in science, math and engineering.
“All of the people who have helped me in my career pushed me to be a better scientist,” he said. “I think that the earlier you reach kids with this field, the more likely they are to participate later on.”
Bruni was recently awarded a Gilliam Fellowship from the Howard Hughes Medical Institute. The fellowship is awarded to doctoral students who have the potential to be leaders in their fields as well as a desire to advance diversity and inclusion in the sciences.
After hearing Bruni give a talk on his work, Thomas J. Yao, a junior in molecular biology, asked if he could come work in the lab. Through the CU Biological Sciences Initiative, Yao is working as a student researcher.
“My role at the Kralj Lab is to see how electrical signals in bacteria change in response to high antibiotic doses,” Yao said. “As a defense mechanism, some bacteria ‘fall asleep’ when submitted to high doses of antibiotics, making it difficult to get rid of them. We’re using microscopy equipment to see how these electrical signals occur in them while they’re changing their physiology in response to the antibiotics.”
The microscope they use is a complex system of lasers and several small mirrors set up on a large table. The bacteria are visible on computer monitors because the researchers express proteins bacteria don’t typically have that are excited by the lasers. This leads the proteins to change their shape and emit light. Researchers study how variations in the light change over time and relate how this changing light is influenced by different aspects of their biology.
“CU has been a wonderful place to do research and Joel has given me room to study what I’m excited to study,” Bruni said. “Studying these basic processes allows us to later down the line apply them to big, complicated problems. The most applicable real-world aspect of our research would be discovering a new antibiotic.”