How far will a scientist travel in pursuit of answers? In the case of Ilana Brito, new assistant professor in the Meinig School of Biomedical Engineering, the answer is: one-third of the way around the globe.
Brito, the Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering, co-authored a report with Massachusetts Institute of Technology professor Eric Alm on “mobile genes” and the role they play in the human microbiome. Mobile genes are genetic material that, unlike that passed from parent to child, moves between organisms by horizontal gene transfer.
In early 2011, Brito – then a postdoctoral researcher working in Alm’s lab at MIT – traveled more than 8,000 miles from Boston to the South Pacific islands of Fiji to study remote, isolated populations and compare the mobile genes within the microbiomes to those of people living in metropolitan North America. The information on North Americans was gathered in 2008 in the Human Microbiome Project of the National Institutes of Health.
The Brito group’s work, “Mobile genes in the human microbiome are structured from global to individual scales,” was published July 21 in Nature.
If this work – collecting genetic material from scores of indigenous people on an island thousands of miles from home – sounds too formidable, that’s understandable. The NIH felt that way, too, Brito said.
“I applied and was turned down for funding,” she said. “The main criticism was that it sounded ‘too ambitious.’ But I just went ahead and did it, thinking that I would figure [the money] out when I got back. It all worked out in the end, but it was a little dicey.”
Eventually, the Broad Institute of MIT and Harvard came through with backing for the work, which broke ground in a couple of different areas. The study of 172 Fijian islanders – called the Fiji Community Microbiome Project (FijiCOMP) – represents the first terabase-scale metagenomic view of the microbiome in the developing world. A terabase is an amount of genetic sequence data equivalent to 10 trillion base pairs.
Brito was in Fiji for six weeks, living with local families and conducting an extensive survey of villagers she met. She mapped out family trees and social networks, noted what medications they took, and recorded exact locations of their homes and drinking water supplies. She also sampled their water and identified who touched livestock, and took samples from those livestock.
She was also “basically going door to door, asking for stool samples,” she said with a laugh, eventually returning home with more than 1,000 genetic samples.
The group’s exhaustive research combined both single-cell sequencing of nearly 200 genomes derived from seven FijiCOMP participants and metagenomics from all of the samples, to identify more than 22,000 mobile genes. It required, to some extent, inventing as they went along.
“About 200 single cells, that’s quite a large study by today’s standards,” Brito said. “The technology to be able to do sequencing on one cell is fairly new and required some new engineering on our part.”
Among their findings, the team reported large differences in mobile gene content between the Fijian and North American microbiomes, with variations consistent with known dietary and behavioral differences between the populations. Those findings support the hypothesis that human activities provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.
For a gene to be transferred into someone’s microbiome, Brito said, the transporting microbe doesn’t even have to survive. Its genes can still be passed on and integrated into another bacteria’s genome.
“It’s thought that that’s primarily the way antibiotic resistance spreads,” she said. “Pathogens acquire resistance from the microbiome. This is actually a fundamental question that I want to continue looking at in my lab.”
Brito said that while the group’s years of research and study answered many questions, it has raised new ones. “It has given us a lot of preliminary data to chew on and figure out the next steps,” she said.
This work was supported by grants from the National Human Genome Research Institute to the Broad Institute, the Center for Environmental Health Sciences at MIT, the Center for Microbiome Informatics and Therapeutics at MIT, the Earth Institute at Columbia University and the Fijian Ministry of Health.