The Challenges of Traditional Cultivation Workflows

Microbiome research could produce an incredible array of products: from novel antibiotics and other drugs, to feed additives for cattle, chickens and swine, to industrial chemicals, to…The list of applications is virtually endless.

These opportunities are incredibly attractive, but there’s a problem that’s slowing us down. Most microbes are difficult to isolate and cultivate. Traditional microbiology techniques and workflows cannot accommodate the rapid expansion in microbiome research labs. Take any sample – soil, stool, ocean – and there may be millions of microbes in each. Any one of these could have great value, but with present technology that sample is exceedingly difficult to pick apart, and significant discoveries could be overlooked.

Isolation and cultivation are critical steps. Without them, it’s hard to determine whether a specific microbe can be useful. Can it support a specific application; does it produce interesting enzymes and/or metabolites; can it be scaled?

Traditional microbiology methods present a number of barriers. First, they’re quite labor intensive. Researchers have to spend their time on the care and feeding of microbes. For example, it might take 5,000 petri dishes to get the statistical heft to power a good study. That’s a lot of streaking, and there’s always the risk that fast-growing strains will overwhelm many of these dishes and suppress other important one’s.

They are also space-intensive. Where are we going to put all of those dishes? This becomes even more prohibitive when the target bacterium is anaerobic. Sometimes experiments have to be staggered because the dishes cannot fit into a single chamber.

After all this effort, perhaps the greatest problem is that these methods are low-yield. It might take months or years to isolate a single strain. If that microbe is useful – awesome. If not, it’s back to the drawing board.

What’s needed is a solution that isolates multiple microbes in parallel. Once separated from the pack, these strains can be grown and studied: proteomics, metabolomics, mass spectrometry, etc.

That’s what GALT is working on. We know there’s gold in those samples – cool chemistry, enzymes, bugs as drugs. We just have to develop a better method to efficiently pan for that gold.

Our high throughput microbiology solution is that method. The answers are there, and we are building new tools for microbiome researchers to find them faster.

Learn more about our early access program and how you can find gold in your samples.

What We are Missing

Movie trailers can tell us a lot about a film. But they’re only two minutes, and only give enough information to pique our interest.

That’s kind of where we are in microbiology. We know there are lots and lots of interesting microbes out in the world: in our guts, on our skin, in the soil and on plants and animals, in the ocean – everywhere. There may be a million microbes in a thimbleful of soil.

On the other hand, researchers have only isolated around one percent of the world’s known microbes. That one percent is the trailer. It intrigues us and makes us want to learn more.

But microbiology is incredibly hard. Some microbes are aerobic, others anaerobic. Some require nutrient-rich media; others prefer nutritional deprivation. Some grow agonizingly slowly, making it difficult for them to compete with fast-growing cousins.

Are these microbes unculturable? Maybe not, we just need to get better at meeting their individual needs. This means developing new tools to better recapitulate the environments for which they evolved.

Traditional microbiology techniques have taken us this far, but it’s unclear whether they can – on their own – take us the rest of the way.

Many labs use a combination of next generation sequencing and in silico analysis to identify potentially interesting microbes. But if scientists really want to understand a microbes’ phenotype, it has to be cultured. That means running old school microbiology workflows that are not scalable, are labor intensive, and don’t always yield the desired results.

It could take months or years to isolate a single strain, and that’s just one strain. There could be dozens or hundreds of potentially interesting microbes in a sample. Getting a complete read on their functional traits could require decades of painstaking work.

At GALT, we are intrigued by the vast possibilities of the microbiome. There may be unique compounds that could fight infectious diseases, promote plant growth to help meet the needs of our expanding global population or enable energy production. But before we get there, we need to find a more efficient and scalable way to isolate and culture these organisms. New improved microbiome research tools are needed to drive our understanding of complex microbial populations, their interactions with each other and their environment, and their potential role in product development.

So that’s what we’re working on: new tools to enable high throughput microbiology workflows that will meet the ever expanding scope of microbiome research.

Learn more about our how we’re bringing scale to accelerate microbiome research.

We are not Alone

As science becomes more sophisticated, we learn that some things we thought were inconsequential are actually quite important. “Junk” DNA is a perfect example. It’s doing a lot more than we previously suspected.

The same is true of the microbiome. Over the years, our understanding has evolved from not being particularly concerned either way, to feeling some mild interest, to “oh wow, these microbes have a crucial impact on our health and wellbeing.” It’s not so much that we share the Earth with microbes – they’re sharing it with us.

Research over the last decade has shown that our resident bacteria contribute to gut, immune and even mental health. There’s a balance of power in and on our bodies – the key word being balance.

This goes way beyond human health. Microbes play a major role in plant growth, impacting food production, animal husbandry and are an emergent force in energy production and other industries.

Microbes produce unique enzymes and metabolites that could find their way into multiple applications – but to enable this, we need to meet them where they live, understand their lifecycle and learn about their function. Quite literally, we have to be able to watch them grow, and be able to do this in a highly parallel manner.

And that’s the complication. Bacteria and other microbes can be difficult to isolate and culture. It might take months, or even years to successfully grow a bacterium of interest. What we need now is a better way to isolate and grow them to gain all-important functional information.

Spoiler alert: That’s what GALT is working on. We believe microbiologists need new high throughput microbiome research tools to rapidly isolate and study microbes so we can learn about their enzymes, metabolites and other interesting molecules. What do they do and how do they do it? How do they live?

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