Bioengineering nonprofit Cultivarium is embarking on a three-year journey to develop tools and resources for scientists studying fungi and archaea, backed by $10 million in funding from the London-based foundation Wellcome Trust.
The open-source tools built by the Massachusetts-based microbe mavericks are meant to unlock the potential for non-model organisms to advance drug development and biodegradation technology, among many other potential applications, Cultivarium cofounder and CEO Henry Lee, Ph.D., told Fierce Biotech in an interview.
There are millions of undescribed fungi in the world, any of which could serve as the source of a new drug. For example, researchers at the National Institutes of Health discovered three tuberculosis-killing compounds late last year by studying fungi living in bogs.
“Cultivarium is uniquely positioned to advance technologies with the focus and speed required to help us better understand fungi and archaea,” Viv Goossens, Ph.D., Wellcome’s research manager, said in an April 24 release. “By developing foundational tools, we can empower researchers to make new discoveries that make a meaningful impact on improving people’s health around the world.”
The nonprofit’s work will focus on three key pillars, Lee said: growth, DNA delivery and community.
It’s a commonly asserted phenomenon in microbiology that many microbes are difficult—or even impossible—to culture in the lab. But the truth is that for many species, scientists have never seriously tried, Lee said.
Since starting work with bacteria, “we've been able to culture more things than we thought, using simpler media than we thought,” Lee said in an interview with Fierce Biotech.
Even less effort has been put on fungi, he added. Cultivarium will use the new funds to cultivate fungi under different types of conditions and document the results for anyone to access.
“We're trying to reduce a little bit of the word of mouth, reduce a little bit of the master-disciple relationship, to be able to create these assets so that anyone can get started in this work,” Lee said.
The Wellcome agreement will also enable Cultivarium to assemble molecular tool kits for editing the genes of different fungi and archaea. This not only includes how to get DNA past the microbe’s cell wall, which can vary from species to species, but also documenting the suite of CRISPR enzymes and gene promoters that work in each microbe.
“We have a suite of technologies that we've built for bacteria, which we'd like to start adapting for fungi,” Lee said. “The fungal researchers, they've done tremendous work already with what we would consider limited resources. We'd like to enrich that for them.”
The ability to edit DNA in fungi can not only power basic scientific research but also give bioengineers the tools to turn fungal cells into little factories that churn out valuable molecules, similar to how genetically engineered bacteria are used to mass produce insulin.
The final piece of Cultivarium’s initiative is to build a network for researchers studying non-model microbes to connect with each other. The group’s resources are available through online repositories like Github and Cultivarium’s own portal, where researchers can get in touch with each other.
Lee said the nonprofit plans to bring together groups of advisors for the different fungi targeted by the program, species that will also be chosen based on input from the research community.
“Right now, what we want to do is really demonstrate that we can make an impact on key non-model fungi that people are interested in today,” Lee said.
Lee and Cultivarium co-founder Nili Ostrov, Ph.D., launched the nonprofit at the end of 2021 after struggling to study a fast-growing marine bacteria called Vibrio natriegens in the Harvard lab of gene editing pioneer George Church, Ph.D., who serves as a scientific advisor for the organization.
“We just ran into all of these inefficiencies,” Lee said. “We wish this tool existed, we wish there was a database for this, we wish that someone would have built this instrument or built this software.”
While the team was ultimately able to use V. natriegens to “amplify DNA and make interesting nanoparticles,” he said, “there's a tremendous need for both basic researchers and people who are looking to translate biotech opportunities to be able to use these tools, cut time, cut resources and get to outcomes faster.”
Cultivarium started working with bacteria and is now moving to the slightly more complex world of fungi and archaea. But Lee doesn’t want to stop there. He envisions working on genetic tools for protists and eventually even more complex organisms like squid and stick insects.
“There's lots of fascinating biology that is relevant for us, but we need to start somewhere,” Lee said.
But no matter what the organism is, Cultivarium’s ultimate goal is to serve the needs of researchers, Lee added, whether they are in academia or the pharmaceutical industry.
“We are technologists, we want to solve other people's problems,” he said. “We are open for collaboration.”