“There’s a saying entrepreneurs live by—Do more than anyone thought possible with less than anyone thought necessary.” These are the words of Dr. Cheri Ackerman, Co-founder and CEO of Boston-based Concerto Biosciences, as she describes her company’s thinking. She and her two cofounders, Dr. Jared Kehe and Dr. Bernardo Cervantes, are doing just that. With the help of an ingenious new technology platform, they are reimagining how humanity interacts with microbes.

MICROBES – IN US, ON US, AND AROUND US

Microbes are everywhere around us: in the soil, in air that we breathe, and all over the human body. Typically, microbes are thought of as harmful. Often, we strive to eradicate the bacteria or “germs” that make us sick with sanitizers or antibiotics.

Millions of microbes form invisible networks all around us that shape the health of our bodies and environments. (Image courtesy of Concerto Biosciences)

Despite popular perception, life as we know it could not exist without microbes. “They aren’t just fascinating from a scientific perspective. They are, in fact, a vital component of global homeostasis. That includes the biosphere at large; that includes every plant, animal, and human being,” Dr. Jared Kehe, Co-founder and Chief Scientific Officer of Concerto Biosciences, explains. “The invisible network of microbes is a complex, dynamic system whose performance depends on the interactions among member microbes, just as a symphony depends on interactions among its instruments. Through millions of years of coevolution, humans have come to depend on that performance. Despite this dependence, we’ve spent the last century indiscriminately killing microbes. So as engineers, we ask: Is there a better way?”  

It was the alarming disconnect between the way we typically kill microbes and the unrealized potential of engineering these complex systems that led to Cheri and Jared partnering and the emergence of the technology behind Concerto. Jared illustrates all the good microbiology can do for humankind: “If we can learn to shepherd microbial communities to perform useful tasks, we gain access to an entirely new frontier of disease treatment, consumer products, crop science, and environment modification.”

With the yearning to better understand these complex systems, the team turned their attention to creating the technology to measure, at unprecedented scale, how microbial interactions drive desirable microbial behaviors. Concerto uses this knowledge to pinpoint “microbial ensembles”, combinations of microbes that work together to perform incredible feats. 

REINVENTING THE WAY HUMANS INTERACT WITH MICROBES

What is stopping us from systematically measuring microbial interactions? The challenge, simply put, is combinatorial math. As Cheri and Jared explain, the sheer number of interactions or combinations that you can create from, say, ~1,000 microbes grows exponentially into the billions as you start constructing subsets of 2, 3, and 4 microbes at a time. 

Existing technology cannot work fast enough to perform such experiments. The best robots we have can only scale upwards of 20,000 combinations per day. Enter the kChip, Concerto’s game-changing technology that as of June 2021, constructs 420,000 combinations per day. Cheri and Jared plan to double this number in 2022.

The kChip technology platform allows for the rapid measurement of millions of microbial interactions. (Image courtesy of Concerto Biosciences)

“The kChip constructs all of the possible combinations from a collection of microbes rapidly and automatically,” says Jared.

The technology works by randomly grouping tiny, color-coded droplets of different microbes into the microwells of a kChip. Millions of these groupings are produced. By color coding each droplet, the team can optically identify the members of each combination. The team can then observe the behavior of each microbial combination, map the full web of interactions, and identify which microbes within that web drive specific functions. “That web presents Concerto with an instruction manual of Nature. We get to use that instruction manual to build things,” Jared says.

The team first set out to map how microbes that live on our skin prevent the microbe Staphylococcus aureus (better known as “Staph”) from over-proliferating and secreting toxins, which are underlying causes of eczema. By identifying the combinations that mobilize a microbial community to suppress the virulence of S. aureus, the team has discovered a microbial ensemble that they plan to develop as an eczema treatment. Jared shares that “this is an opportunity to treat skin disease by placating misbehaving strains like S. aureus rather than simply killing everything that lives there. That’s a more elegant and powerful solution than warfare.”

MATLAB AS AN ESSENTIAL STARTUP RESOURCE 

Like many engineers, Jared first encountered MATLAB during his undergraduate studies at UC San Diego. Through graduate school at MIT, where the kChip was born, MATLAB became his “go-to for any and all analysis and coding.” 

The original academic team that developed kChip, which included Jared, Cheri, their former labmate Anthony Kulesa, and their advisor Paul Blainey, used MATLAB for multiple aspects of the platform development. Very early on, MATLAB was used to explore different configurations to optimize the geometry design of the microwells. The team uses MathWorks tools to extract information about the behavioral attributes of the microbe combinations. “MATLAB is a really good image analysis tool,” comments Jared. “Translating raw images into .csv files that organized the data was the starting point for the much deeper analysis of the underlying microbial ecology.”

Fluorescent analysis of kChip microwells extracts how each microbial combination affects a virulence readout. (Image courtesy of Concerto Biosciences)

As a member of MIT Venture Mentoring Services, Concerto Biosciences had a connection to the MathWorks accelerator program, which provides early-stage startups with access to free MATLAB software and support. As an early stage, resource strapped startup, “we had literally nothing and to have a workhorse in place to handle any data was essential,” Jared explains when considering the importance of having access to MATLAB as a tool.

LOOKING TOWARD A HEALTHIER FUTURE  

Following the successful finding of their first ensemble for skin health this past year, the team is looking ahead. They plan to continue advancing their first product and sharing with patients, seeing how well it performs and assessing its beneficial properties. Cheri foresees many uses for the technology, hoping especially to move into women’s health in the next year and “broadly across all of the applications you can imagine,” she says. “We want to make the platform faster and cheaper and open up this new class of products to other companies who want to collaborate with Concerto.” 

The startup is also expanding its discovery team, looking for the right fit of people to join. “The fundamental reward for me is building the culture of this company, being one of the people that gets to decide what we value as a group of people…creating an environment with curiosity and intellectual sparring, but also caring about each other.” Cheri closes on what she loves about building Concerto Biosciences: “I often say the reason that I left academia to do this startup was the specific people that were committed to the startup. What a unique moment in time to have these people aligned and ready to jump into this.”

You can learn more about Concerto Biosciences at https://www.concertobio.com.