Q&A with Chathuri Kombala

Published April 11, 2022, by Judith Van Dongen

We’ve all done our share of remote work these past two years due to the pandemic, but for Chathuri Kombala—a postdoctoral research associate in the College of Medicine—it’s an essential part of the job. As the first joint postdoc in a newly established gut microbiome science partnership between WSU and Pacific Northwest National Laboratories (PNNL), Kombala has been working at PNNL’s main campus in Richland since first joining in August 2020. There, she has access to all the tools and technologies she needs to advance her research into the link between the gut microbiome (i.e., microbes that live in the human gut) and the circadian (or 24-hour) rhythms that help keep the human body on a regular day/night schedule.

What drew you to this joint postdoctoral position in microbiome science?
My educational background is in chemistry. I completed an undergraduate degree in chemistry in my home country of Sri Lanka before completing a master’s in organic chemistry at Sam Houston State University in Texas and a Ph.D. focused on biological chemistry at the University of Arizona. As part of my Ph.D. research, I developed chemical reagents for molecular imaging of biological samples. I really wanted to expand my knowledge in biology and bioanalytical chemistry during my postdoctoral training. When I saw the job post for the joint postdoc position, it seemed like a great fit to achieve my career goals.

What type of work does your postdoc entail?
I use chemical biology approaches to understand the link between circadian rhythms and the gut microbiome. For example, I use organic synthesis to develop chemical compounds that we can then use as tools to understand the activity of certain enzymes in the gut. One enzyme I’ve been looking at is bile salt hydrolase, which is one of the key microbial enzymes involved in bile acid metabolism. [Bile acids play an essential role in the digestion and absorption of fats and fat-soluble vitamins. Ed.] As part of my work, I developed a chemical compound that can specifically detect bile salt hydrolase activity. We tested it on fecal samples of mice, and we found that the compound we developed could successfully detect even small amounts of bile salt hydrolase activity using relatively small samples. In addition, we saw that bile salt hydrolase activity levels change throughout the day, and this is directly influenced by feeding schedules. The human body depends on microbes to influence bile salt hydrolase, so this tells us that eating at a different time of day changes the gut microbiome, which in turn alters metabolism in the mice themselves.

So how might your work eventually contribute to improving human health?
Knowing more about the activity of microbes can help us better understand disease and could serve as a basis for the development of therapeutics. The work we do is especially relevant to people who have disturbed circadian rhythms, including those who work night shifts. Just as an example: if activity levels of certain enzymes—such as bile salt hydrolase—are altered in shift workers compared to individuals with normal circadian rhythms, we could use microorganisms that influence this enzyme activity as a probiotic to get 24-hour rhythms in the gut back to normal. That’s important because previous research conducted by our team suggests that the reason why night shift workers are more susceptible to obesity, diabetes, and metabolic disorders may be that the master biological clock in their brain is out of sync with the rhythms in their digestive organs. So if we can resynchronize those digestive rhythms we could potentially improve health and prevent disease in night shift workers. What’s more, new probiotic strains developed as therapeutics could be used to actively treat certain diseases. For example, bile acid metabolism is linked to cardiac disease and liver function, so a probiotic that can boost bile salt hydrolase activity could potentially be used in the treatment of those diseases. Having a chemical compound in hand with which we can measure bile salt hydrolase is tremendously helpful in the development of such probiotics.

How do you feel about the experience you have gained so far?
I have gained a lot of new experience in biology, bioanalytical chemistry, microbiology, and the biology of different types of diseases, especially those tied to disturbed circadian rhythms. It has been super helpful for me to improve my skills in those areas. I’m especially proud of my project on bile salt hydrolase activity, which I was able to finish and send out for publication in a really short amount of time. I want to thank the Sleep and Performance Research Center team and the College of Medicine at WSU and the chemical biology team at PNNL for helping me succeed. Special thanks go out to my mentors Kris Brandvold at PNNL and Hans Van Dongen at WSU, who helped guide me so I could achieve these groundbreaking results.

This interview has been edited and condensed for clarity.