The beauty of what science can do when urgently needed

Nili Ostrov has always been passionate about finding ways to use biology for practical purposes. So perhaps it wasn’t surprising that, when the COVID-19 pandemic hit during her postdoctoral studies, she went in the opposite direction from most people, moving to New York City to work as the director of molecular diagnostics in the Pandemic Response Lab, providing COVID-19 tests and surveilling viral variants. She was inspired by seeing what scientists could accomplish and how much they could help when under pressure.

Now the chief scientific officer at Cultivarium in Watertown, Massachusetts, Ostrov is bringing that sense of urgency to fundamental problems in synthetic biology. Cultivarium is a non-profit focused research organization, a structure that comes with a finite amount of time and funding to pursue ‘moonshot’ scientific goals, which would usually be difficult for academic laboratories or start-up companies to achieve. Cultivarium has five years of funding, which started in 2022, to develop tools to make it possible for scientists to genetically engineer unconventional model organisms — a group that includes most microbes.

Typically, scientists are limited to working with yeast, the bacterium Escherichia coli and other common lab organisms, because the necessary conditions to grow and manipulate them are well understood. Ostrov wants to make it easier to engineer other microbes, such as soil bacteria or microorganisms that live in extreme conditions, for scientific purposes. This could open up new possibilities for biomanufacturing drugs or transportation fuels and solving environmental problems.

What is synthetic biology and what drew you to it?

Synthetic biology melds biology and engineering — it is the level at which you say, “I know how this part works. What can I do with it?” Synthetic biologists ask questions such as, what is this part useful for? How can it benefit people or the environment in some way?

During my PhD programme at Columbia University in New York City, my team worked with the yeast that is used for brewing beer — but we asked, can you use these yeast cells as sensors? Because yeast cells can sense their environment, we could engineer them to detect a pathogen in a water sample. In my postdoctoral work at Harvard University in Cambridge, Massachusetts, we investigated a marine bacterium, Vibrio natriegens. A lot of time during research is spent waiting for cells to grow. V. natriegens doubles in number about every ten minutes — the fastest growth rate of any organism.

Could we use it to speed up research? But using V. natriegens and other uncommon research organisms is hard work. You have to develop the right genetic-engineering tools.

How did the COVID-19 pandemic alter your career trajectory?

It pushed me to do something that I otherwise would not have done. During my postdoctoral programme, I met Jef Boeke, a synthetic biologist at New York University. In 2020, he asked me whether I wanted to help with the city’s Pandemic Response Lab, because of my expertise in DNA technology. I’m probably one of the only people with a newborn baby who moved into Manhattan when COVID-19 hit.

That was an amazing experience: I took my science and skills and used them for something essential and urgent. In a couple of months, we set up a lab that supported the city’s health system. We monitored for new variants of the virus using genomic sequencing and ran diagnostic tests.

Seeing what science can do when needed — it was beautiful. It showed me how effective science can be, and how fast science can move with the right set-up.

How did that influence what you’re doing now with Cultivarium?

COVID-19 showed me how urgently needed science can be done. It’s about bringing together the right people from different disciplines. Cultivarium is addressing fundamental problems in science, which is usually done in academic settings, with the fast pace and the dynamic of a start-up company.

We need to make progress on finding ways to use unconventional microbes to advance science. A lot of bioproduction of industrial and therapeutic molecules is done in a few model organisms, such as E. coli and yeast. Imagine what you could achieve if you had 100 different organisms. If you’re looking to produce a protein that needs to be made in high temperatures or at an extreme pH, you can’t use E. coli, because it won’t grow.

How is Cultivarium making unconventional microbes research-friendly?

It took my postdoctoral lab team six years to get to the point where we could take V. natriegens, which we initially didn’t know how to grow well or engineer, and knock out every gene in its genome.

At Cultivarium, we’re taking a more systematic approach to provide those culturing and engineering tools for researchers to use in their organism of choice. This kind of topic gets less funding, because it’s foundational science.

So, we develop and distribute the tools to reproducibly culture microorganisms, introduce DNA into them and genetically engineer them. Only then can the organism be used in research and engineering.

Developing these tools takes many years and a lot of money and skills. It takes a lot of people in the room: a biologist, a microbiologist, an automation person, a computational biologist, an engineer. As a non-profit company, we try to make our tools available to all scientists to help them to use their organism of choice for a given application.

We have funding for five years from Schmidt Futures, a non-profit organization in New York City. We’re already releasing and distributing tools and information online. We’re building a portal where all data for non-standard model organisms will be available.

Which appeals to you more — academic research or the private sector?

I like the fast pace of start-up companies. I like the accessibility of expertise: you can bring the engineer into the room with the biologists. I like that you can build a team of people who all work for the same goal with the same motivation and urgency.

Academia is wonderful, and I think it’s very important for people to get rigorous training. But I think we should also showcase other career options for early-career researchers. Before the pandemic, I didn’t know what it was like to work in a non-academic set-up. And once I got a taste of it, I found that it worked well for me.