Last week was a monumental one for me – I said goodbye to my old lab, where I’ve worked for the past 5 years. It was harder than I thought it would be to leave. Grad school was rough at times, but it was an overwhelmingly positive and rewarding experience, due in no small part to the people in the lab.
That said, I’m incredibly excited about my new position, and the new lab I’m joining, not least because the research I’ll be doing will be super relevant to this blog. I’m in a lab that studies the microbiome – the diverse microbial communities – that live on the rinds of cheese!
Why on earth would anyone want to do that (well, besides the obvious fact that cheese is delicious that is)?
A great deal of energy and research money is being spent to understand the human microbiome. There are something like 100 trillion (with a T) microbes living in your gut, meaning bacteria outnumber your own cells by a factor of 10 to 1. Even more staggering, the number of microbial genes outnumber your paltry ~20,000 by a factor of 100.
That wealth of genetic information would be interesting to understand in its own right, but that’s not the reason we’re sinking millions of dollars into researching it. Those gut-dwellers have a profound impact on human health, affecting everything from obesity and diabetes to allergies and autoimmune disorders. But there’s a problem: gut microbial communities are really hard to study.
Challenges of Gut Microbes
There are a number of things that make studying the gut microbiome hard. First: it’s incredibly diverse. There are thousands of species, many of which have not been characterized. We don’t even know what all of our own genes do, let along the hundreds of thousands of microbial genes in the gut. Second: many of the microbes are not culturable, or at least not easy to culture. It’s tough to study microbes if we can’t grow them in the lab. Many species in the gut die when exposed to oxygen, necessitating the use of “anaerobic” chambers that seal off the atmosphere entirely.
The third and perhaps most difficult challenge is that the natural habitat of these microbes is in an animal gut. Sure, we have mice and other model organisms in which to study these communities, but if we want to study particular microbes, we have to create what are called “germ free” mice. Normally, animals begin to be colonized by microbes the instant they are born. In order to make a mouse free of external microbes, they must be treated with massive doses of antibiotics and moved to a sterile bubble immediately after birth. These mice can be recolonized with small groups of microbes, but germ free mice are quite unhealthy – it turns out that the denizens of our intestines are important for keeping us healthy in ways we still don’t fully understand.
Cheese as a Model
We need to understand how diverse communities of microbes interact, but doing so in the gut is hard. Why not turn to a model system, where diverse microbial communities interact, but in an environment that’s easier to study? We have a long history of using model systems in biology – the mice I mentioned up above are models. Cheese rinds contain diverse communities of microbes, but they are not quite as complex as those in the gut, and every single microbe can be grown in the air, at room temperature, on a simple substrate.
So what might we learn from these model communities? Quite a lot it turns out – the lab already has a pretty big paper in press, though I’m not sure how much I can reveal about those findings just now (it sucks that one ever has to keep science secret – but that’s the world we live in). But speaking generally, one of the most important but understudied aspects of microbial communities is how individual bugs interact with each other. It’s not that people aren’t investigating because they’re lazy – it’s just really hard. Scientists typically like to take a reductionist approach to problems, but what if there are species of microbes that depend upon one another for some metabolic process? Just trying to grow one or the other on its own won’t work. If you were trying to figure this out in a mouse, you’d have to use the germ-free ones (which are super expensive), and then do pair-wise combinations of potentially thousands of different species. No lab in the world has that kind of money (let alone the time).
But with cheese, it’s much easier! This lab has learned how to make cheese in tiny little wells (96 wells fit in ~ 3 x 4 inch plastic plate), so you can test hundreds of conditions at a time with a little patience and good planning. The principals about microbial interactions that we learn from the cheese may allow us to design better experiments to investigate the microbial communities in our gut.
It’s also worth noting that global cheese consumption tops 5.4 million metric tons per year (in the US, we eat ~ 30 lbs of cheese per person per year) – maybe it’s worth knowing exactly what we’re eating?
I’ve got a potential project to work on, and I’m in the process of setting it up. I hope to be able to share more details with you in the future, but I’ll definitely be sharing the cool science I’m learning reading papers in an entirely new field. My contribution to this blog is about to get a whole lot cheesier, and a whole lot microbio…log…ier… or something. Happily, my project maintains a connection to immunology and host-pathogen interactions, but more on that in another post. Stay tuned!
Secrets of the Universe: Past, Present, FutureX