Manipulating Microbiota: A Synthetic Biology Exploration of the Gut

33553646_lMicrobial cells outnumber the cells of our own bodies approximately 10:1, these microbes that live on our skin and along the epithelial linings of our internal tubes make up our microbiota*, and they can have major effects on our health. Most of our microbiota are commensal organisms, living in harmony with our body, but if you suppress our immune system or greatly reduce their populations with large doses of antibiotics, and you will soon see the effects of disrupting our microbiota.

There is much interest in the microbiota that inhabit our bodies. For instance several studies have indicated that intestinal microbes can play a big part in obesity, with changes in the makeup of the microbiota being a major risk factor (1). But many of these organisms are hard to learn about—the ones that inhabit the deep folds of our gut thrive in moist, warm, anaerobic conditions with lots of specialized nutrients, conditions that are very hard to replicate in the laboratory. For that reason, we don’t know much about many of the microbes that are the most abundant within us.

The Human Microbiome Project begun in 2008 by the National Institutes of Health (2) seeks to understand human microbiota and their relationship to human health. To do this, the researchers leading the project took a metagenomic approach—using advanced DNA sequencing technologies to sequence the genomes of human microbiota and get a look at the human microbiome—without culturing the microbes.

But to truly understand their biology, and to perhaps exploit what we learn to enhance human health we need to be able to manipulate these organisms. In particular, biologists who are interested in synthetic biology would like to use these micro-organisms to monitor what is going on in our bodies, particularly our guts. What better monitor for these hard-to-access places than an organism that is already well adapted to live there?  Continue reading “Manipulating Microbiota: A Synthetic Biology Exploration of the Gut”

Mining Genomes for Antimicrobials

searching for new antibioticsWhile looking through some “Top Ten” lists of the various science stories and discoveries of 2014, I came across a paper, published in Cell in September, describing a new approach to the search for antimicrobials. The paper’s authors screened the vast amount of genomic data from the human microbiome project against known sequences to find genes with homology to existing small molecule drug candidates.

The authors reasoned that any genes that were common across many species would be more likely to affect conserved microbe:host or microbe:microbe interactions. Having identified a large group of these gene clusters, they then homed in on a subset that was commonly found in the microbiome of healthy individuals. As a proof-of-concept, they then identified and characterized a thiopeptide molecule produced by the bacterium Lactobacillus gasseri  and showed that it had the expected antimicrobial activity. The Cell paper was the first report of the characterization of any small molecule drug candidate isolated from the human microbiome. Continue reading “Mining Genomes for Antimicrobials”

Christensenellaceae—A Natural Way to Stay Thin?

microbiome studies show how bacterial colonists influence healthA study published in the Nov 6 issue of Cell outlined results suggesting that an obscure family of bacteria colonizing the human gut may be inherited and may also have a direct influence on body weight. The paper is the first to identify such an association and to link a particular microbial colonist with lower BMI. Continue reading “Christensenellaceae—A Natural Way to Stay Thin?”

About the Wild Life in Our Homes (at least the single-celled kind)

The initial paper from the Wild Life in Our Homes study by Dunn et al. found a correlation between the presence of dogs and specific bacterial communities on pillowcases and TV screens.
The initial paper from the Wild Life in Our Homes study by Dunn et al. found a correlation between the presence of dogs and specific bacterial communities on pillowcases and TV screens.

Back in the fall, I received a sampling kit, an Informed Consent form and instructions for collecting samples for the Wild Life In Our Homes citizen science project. I carefully swabbed the requested surfaces: exterior and interior door trim, kitchen counter tops, pillowcases, etc., and sent my samples in. I later received confirmation that my samples had been received and again later confirmation that they were being analyzed.

The first paper from this project has been published by Dunn et al. in PLOS ONE (Home Life: Factors Structuring the Bacterial Diversity Found within and between Homes). This initial report covers the first 40 homes sampled, all from the Raleigh-Durham, NC, USA area. Volunteers sampled their homes in the Fall of 2011, collecting specimens from nine areas: cutting boards, kitchen counters, refrigerator, toilet seat, pillowcase, door handle, TV screen, and interior and exterior door trim. The scientists used direct PCR and high-throughput sequencing to sequence the bacterial 16S rRNA gene from the submitted samples. By doing this they were able to estimate the diversity within each sample—they did not distinguish between live and dead organisms, and they did not sequence anything other than the bacterial 16SrRNA, so this study is limited to bacteria. Continue reading “About the Wild Life in Our Homes (at least the single-celled kind)”

My Microbiome Made Me Do It

When I was in school I learned that there were two different kinds of bacteria, the nasty ones (pathogens) that could make you sick and the nice ones (commensals), which simply colonized you and did nothing much except occupy a spot that could otherwise be taken up by a pathogen. Any role for those commensal bacteria in health and disease was assumed to be no more than that of a harmless squatter. In recent years, studies of this benign microbial population (microbiome studies) have begun to reveal many more intriguing details about how they affect our health and wellbeing. Maybe it’s not so surprising that “good” bacteria could be good for our health—but could they actually affect how we behave? This month, a review in Science summarized new findings that indicate that this is indeed the case—at least for certain animal populations. Could it be true for humans as well? Could our colonizing organisms actually influence how we feel and what we do? Continue reading “My Microbiome Made Me Do It”

Dark Matter, Rosetta Stones and Hordes of Beasties

Key regulatory roles are being identified for non-coding DNA sequences, once considered "junk".
The more you know, the more you find out about how much you still don’t know. So goes the old saying. A recent New York Times article nicely illustrated the practical outworking of this phenomenon in the context of cancer research. The article highlighted several recent papers and reviews showing how much progress has been made over the last ten years, and illustrating how the focus has changed to incorporate not only research on protein-coding sequences, but also the “dark matter” of noncoding RNAs and the potential contributions of genes from the millions of bacteria that colonize the human body.

In 2000, a review describing six key traits of cancer cells was published in the journal Cell, it is one of the most cited papers from that journal. In March of this year, the same authors published an update entitled Hallmarks of Cancer: The Next Generation describing current knowledge of the mechanisms underlying the same six traits, and adding two new ones. Continue reading “Dark Matter, Rosetta Stones and Hordes of Beasties”