Researchers are finding more metabolites than anyone realized existed in datasets, but the limitations of existing tools mean we could be missing some critical ones, says Michael Bielski, CEO of newly launched startup Metablify.
Metabolites are small molecules found in cells, tissues and organisms that interact with biological processes; identifying these small molecules could enable more rapid development of everything from cancer drugs to biopesticides.
“Every new metabolite in a sample is potentially a new drug, a new biomarker, something that can enhance crop yields. So every time we miss them, we’re just missing a whole new path of research, potentially,” says Bielski.
With that idea in mind, Metablify officially launched this week out of the Danforth Technology Company (DTC), a subsidiary of the Donald Danforth Plant Science Center in St. Louis, Missouri.
The startup was founded by Danforth Center plant scientists Ivan Baxter, PhD, Allen Hubbard, PhD and Louis Connelly as well as Bielski. Through the Metablify platform, the team hopes to give researchers the ability to sift through the thousands of metabolites that could exist in an experiment using LC/MS data processing algorithms and pinpoint the most important.
He says Metablify has “an opportunity to disrupt the LC/MS landscape,” referring to the analytical chemistry technique that uses liquid chromatography (the “LC”) and mass spectrometry (“the MS”) to separate, identify, and quantify compounds in complex mixtures.
PCR for metabolites
Metablify began as a mistake.
“We had done this really large metabolomics experiment with high-throughput profiling of the metabolites in biological samples,” Baxter tells AgFunderNews, adding that the experiment ended up with 3,800 samples to process.
“We realized that the current software [for handling this process] capped out at about 400 samples. So we were in real trouble because we’d designed the whole experiment to be about doing all the samples at once and be able to compare across the whole spectrum.
Hubbard says he spent a lot of time trying to use current software to make the experiment work, finally concluding that what the team needed was PCR for metabolites.
Formally known as a polymerase chain reaction, PCR is used in DNA and RNA sequencing to, as Hubbard puts it, “amplify the heck out of the thing you’re trying to measure.”
But chemicals, a category in which metabolites can be classed, “can’t be multiplied,” says Hubbard. “[We needed] a technology that allows us to boost signal-to-noise ratios in metabolites the way PCR is used to actually physically increase DNA to get you more signal.”
From left: Ivan Baxter, PhD, Allen Hubbard, PhD and Louis Connelly. Image credit: Metablify/Danforth Technology Center
In a nutshell, the Metablify platform takes data from the different metabolite samples in an experiment and overlaps them. This strengthens the signal of the research subject, making it easier to detect.
Bielski likens it, on a high level, to viewing “a faint galaxy at a very far distance.”
“If you take one picture, it’s tough to figure out what’s going on. But if you take lots and lots of pictures, and you’re able to stack and overlap them in a way that that makes sense and aligns, the information starts to come out of it, and the noise disappears.
“This gets more complicated as the data sets get larger, which is where research is going,” he adds, underscoring the current need for platforms like Meablify’s.
Bielski says the platform could potentially be used for new drugs, new targets for drugs, personalized medicine, or biomarkers.
In agriculture, the platform could assist with enhancing crop yields, dealing with drought resistance or providing new approaches to biological crop protection products.
“It’s really about uncovering this treasure trove of information that we funnel downstream to all of the researchers that are really excited about solving these problems,” he notes. “The end result of this is that we find things that people have been missing in the past, which now can start a whole new research pathway.”
“It could be anything where you’re doing metabolomics,” adds Baxter of Metablify’s use cases. “That could be a lot of ag, you have a lot of drug companies and pharmaceutical companies, personalized medicine, and industrial processes like fermentation.”
“A clear roadmap to expanding’
Metablify’s initial investors include DTC and QRM Capital. So far, the company has received four grants from the Danforth Center’s proof-of-concept fund totaling $200,000 and $500,000 from DTC.
Early seed money came from the Danforth Center’s Big Ideas 3.0 competition, which Metablify won in late 2023.
Currently, the team is focused on building up its partnerships and collaborations to continue validating its technology, says Bielski.
“We have really good internal validation. Part of being a startup is now to go outside of the building and talk to the rest of the world and let them know what you have and what you’re doing.”
“There is a clear roadmap to expanding the types of customers we could serve with this,” adds Baxter. “The first product is designed for one type of LC/MS machine; there are four or five other types on the market. There are additional steps we want to implement to get datasets on machines that aren’t as sensitive or where their chromatography isn’t as good.”
“Once we’ve shown [the tech] off to collaborators, we want to keep expanding that circle,” he adds. “Pretty soon we want to start actually selling it to people.”