Beyond the Genome: Enough to make your skin crawl

Julie Segre is interested in what makes us itch. Bringing together the fields of dermatology, immunology, and microbiology, Dr. Segre, a senior investigator at the National Human Genome Research Institute, is studying the relationship between people and the bacteria and other microscopic organisms (microbes) living on their skin. Dr. Segre, who spoke at this year’s “Beyond the Genome” conference here in Boston, is especially interested in people with eczema and the unique microbial populations they harbor.

The NHGRI’s Human Microbiome Project (HMP) brings together researchers interested in the microbes on and within the human body. To catalog these critters, researchers are using DNA sequencing, which Dr. Segre describes as the new microscope for microbiologists. Just as an actual microscope allows us to peer into a world that’s invisible to the naked eye, DNA sequencing is helping researchers distinguish the indistinguishable and more accurately determine the makeup of our microbial populations. Scientists can of course take samples from the skin and culture the organisms found there, but some microbes grow faster than others, potentially skewing the makeup of the culture. DNA sequencing on the other hand gives a more accurate census of our microbes.

A lot of dermatological conditions are site specific. Dr. Segre gave the example of a rash on the inside of the elbow – eczema – versus on the outside of the elbow – psoriasis. “Now we’re putting a map of microbes onto those dermatological patterns and beginning to say, ‘Why is it that certain diseases manifest in certain body sites?’” DNA sequencing has shown us that microbes are not evenly distributed over our skin. There are certain neighborhoods with distinct populations – for instance, our back may have a very different population of microbes than the skin behind our ear.

Eczema – red, itchy patches of skin – affects about 15 percent of children (and about two percent of adults). People with eczema often develop other conditions including asthma and hay fever. There are a number of treatments for the condition – in extreme cases, patients can be treated with antibiotics, steroids, or even baths of diluted bleach to help get rid of microbes. “There are many treatments for eczema, but we don’t know which ones to give to which patients,” Dr. Segre explained.

Dr. Segre and her colleagues have been studying kids with eczema over time, looking at the microbes inside their elbows and behind their knees before, after, and during eczema flare-ups. Dr. Segre showed a chart of a multitude of colors, each representing a different type of microorganism. During flare-ups, the whole chart seemed to turn pink – the color that represented Staphylococcus, or staph, the same bacteria that causes staph infections. Doctors have long known that kids with eczema are Staph colonized. However, as Dr. Segre explains, "now we can see that even before and after a flare-up, the children with eczema didn’t have the same population of microbes that healthy children did. Our goal is to restore these kids' microflora to normal and prevent future disease flare-ups." Dr. Segre and her colleagues hope that by sequencing and identifying microbial populations, they’ll be able to help match the right treatment to individual patients.

Genome sequencing work for the Human Microbiome Project – which includes microbes from the nose, mouth, gut, and reproductive organs/urinary system in addition to skin – is being done at several sequencing centers, including the Broad Institute. You can read about progress on this project here or read a recap of Bruce Birren’s Midsummer Nights Science talk entitled “Meet Your Microbes” here.