Q: What drew you to research microbes in extreme environments, and what are the challenges in studying them?
A: Extreme environments are great places to search for interesting biology. I desired to be an astronaut growing up, and the closest thing to astrobiology is examining extreme environments on Earth. And the one thing that lives in those extreme environments are microbes. During a sampling expedition that I took part in off the coast of Mexico, we discovered a colourful microbial mat about 2 kilometers underwater that flourished since the bacteria breathed sulfur as a substitute of oxygen — but not one of the microbes I used to be hoping to check would grow within the lab.
The most important challenge in studying microbes is that a majority of them can’t be cultivated, which implies that the one strategy to study their biology is thru a technique called metagenomics. My latest work is genomic language modeling. We’re hoping to develop a computational system so we are able to probe the organism as much as possible “in silico,” just using sequence data. A genomic language model is technically a big language model, except the language is DNA versus human language. It’s trained in an identical way, just in biological language versus English or French. If our objective is to learn the language of biology, we must always leverage the variety of microbial genomes. Despite the fact that we have now lots of data, and at the same time as more samples develop into available, we’ve just scratched the surface of microbial diversity.
Q: Given how diverse microbes are and the way little we understand about them, how can studying microbes in silico, using genomic language modeling, advance our understanding of the microbial genome?
A: A genome is many tens of millions of letters. A human cannot possibly have a look at that and make sense of it. We will program a machine, though, to segment data into pieces which are useful. That’s kind of how bioinformatics works with a single genome. But in the event you’re a gram of soil, which might contain 1000’s of unique genomes, that’s just an excessive amount of data to work with — a human and a pc together are vital so as to grapple with that data.
During my PhD and master’s degree, we were only just discovering recent genomes and recent lineages that were so different from anything that had been characterised or grown within the lab. These were things that we just called “microbial dark matter.” When there are lots of uncharacterized things, that’s where machine learning could be really useful, because we’re just on the lookout for patterns — but that’s not the top goal. What we hope to do is to map these patterns to evolutionary relationships between each genome, each microbe, and every instance of life.
Previously, we’ve been occupied with proteins as a standalone entity — that gets us to an honest degree of knowledge because proteins are related by homology, and due to this fact things which are evolutionarily related might need an identical function.
What is understood about microbiology is that proteins are encoded into genomes, and the context wherein that protein is bounded — what regions come before and after — is evolutionarily conserved, especially if there’s a functional coupling. This makes total sense because when you have got three proteins that have to be expressed together because they form a unit, you then might want them situated right next to one another.
What I need to do is incorporate more of that genomic context in the way in which that we seek for and annotate proteins and understand protein function, in order that we are able to transcend sequence or structural similarity so as to add contextual information to how we understand proteins and hypothesize about their functions.
Q: How can your research be applied to harnessing the functional potential of microbes?
A: Microbes are possibly the world’s best chemists. Leveraging microbial metabolism and biochemistry will result in more sustainable and more efficient methods for producing recent materials, recent therapeutics, and recent forms of polymers.
However it’s not nearly efficiency — microbes are doing chemistry we don’t even know how you can take into consideration. Understanding how microbes work, and having the ability to understand their genomic makeup and their functional capability, will even be really essential as we take into consideration how our world and climate are changing. A majority of carbon sequestration and nutrient cycling is undertaken by microbes; if we don’t understand how a given microbe is capable of fix nitrogen or carbon, then we’ll face difficulties in modeling the nutrient fluxes of the Earth.
On the more therapeutic side, infectious diseases are an actual and growing threat. Understanding how microbes behave in diverse environments relative to the remainder of our microbiome is actually essential as we expect in regards to the future and combating microbial pathogens.
