Biochemistry assistant professor Ophelia Venturelli recently received funding for her proposal to the Army Research Office Young Investigator Program. Titled “Large-scale mapping and modeling of human gut microbiota stability and activity,” her research project seeks to develop new technologies to study microbiomes.
The United States Army Research Office is part of the Army Research Laboratory, overseen by the Department of Defense. Microbiomes are the collection of microbes — bacteria, viruses, fungi, and more — in a given environment. The human gut microbiome is a popular study area because it relates to human health. Other researchers study the microbiome of plants, animals, or the soil. Microbiomes carry out interesting functions like making antibiotics to attack each other or producing compounds that can be used as biofuel so they are of great interest to biochemists.
The Young Investigator Program’s goal is to support the research of young academic faculty members, particularly those who have had their Ph.D. for less than five years. The three-year award provides $120,000 each year.
“Our current technologies for measuring microbial interactions are very limited,” explains Venturelli, who is an affiliate of the Wisconsin Energy Institute. “The current methods are low throughput and only allow us to study interactions between a small number of microbes.”
Her lab’s new approach uses droplet-based microfluidics, meaning the researchers can encapsulate entire microbial communities into tiny droplets to study them. In the tiny emulsions, the microbes can be cultured, sorted, merged, and analyzed. This method can far surpass the capabilities of the standard plate-based methods currently used.
Illustration by Ophelia Venturelli, biochemistry assistant professor
Microbiomes contain hundreds if not thousands of different microbes and so far only combinations of a dozen or so species have been studied. As the systems get more complex, the ways the microbes interact and communicate also get more complex. Venturelli’s project hopes to fill this gap with a scalable approach that allows scientists to interrogate microbial interactions in complex microbiomes.
“We want to get to a place where we aren’t limited necessarily by the dimensions of the microbial community,” she says. “We plan to integrate this method with next generation sequencing to elucidate the composition of the consortia in the droplets.”
She adds that one of the big questions in the field of microbiome research is understanding how exactly community dynamics unfold. She wants to parse out exactly which microbes perform different functions and how.
If they can understand how the microbes are talking to each other, they can better understand how to control elements of the microbiome. This would allow them to possibly manipulate the biochemistry of microbiomes and their structure and function. By gathering data with their new technologies, and combining that with powerful mathematical modelling, Venturelli, who joined the Department of Biochemistry in 2016, and her lab hope to make headway in harnessing the potential of the microbiome.
“We are going to start with synthetic communities but future work could apply to our method to decipher interactions in natural microbial communities or screen combinatorial communities for target functions,” she says. “We could optimize the communities that produce target molecules such as biofuels or molecules for enhancing human health. In terms of the U.S. Army, they may be interested in optimizing human performance in the future. But it all has to start with this basic technology for studying these complex interactions."