THE BRITO LAB
OF HORIZONTAL GENE TRANSFER
IN THE MICROBIOME
Mobile genetic elements typically comprise antibiotic resistance genes, virulence factors, selfish elements and even metabolic genes. They are passed between bacteria within the microbiome and it is now thought that pathogens acquire these elements from commensal microbiota that they interact with. Surprisingly little is known about the dynamics and factors that impact the transfer of mobile elements in the microbiome, mainly because the technology hasn't existed.
The Brito lab is pioneering new technologies that allow us to peer into the gut microbiomes of humans, animals and even environmental microbiomes to understand gene flow in these natural microbial communities. We're using experimental and computational approaches in the hope that our work will will enhance our understanding of microbial ecology and inform current efforts to combat antibiotic resistance.
EXPOSING THE WORLD OF
One of the most important questions in microbiome research today is: how--by what mechanism--do microbes impact host health? We recently developed a computational approach that leverages known interspecies protein-protein interactions to answer this question. Our approach implicates thousands of bacterial proteins in specific pathophisological mechanisms related to type 2 diabetes (T2D), colorectal cancer (CRC), obesity and inflammatory bowel disease (IBD), among others. We are pursuing multiple lines of investigation to determine how to translate these findings into novel therapeutics and diagnostics for microbiome-related diseases.
AND THE HUMAN MICROBIOME
How transmissible is the microbiome? In some situations it appears static and stable, for months and even years. Yet, its composition is also molded by certain experiences and interactions. We are applying strain-level methodologies to tease apart the promiscuous bacteria from those that take up long-term residence in a single host. We want to use this information to better understand how microbiomes evolve over long and short timespans. But this data can also be used to develop better live bacterial therapeutics-- those that can inconspicuously integrate into a microbial community and stably associate with a single person for as long as they need the benefit.
SYNTHETIC SOLUTIONS TO
As the microbiome is implicated in a growing list of health conditions, so is the desire for ways to poke and prod the microbiome to achieve a specific outcomes. Yet, we currently lack the tools necessary for these outcomes to be robust, reliable and predictable in this complex environment. To meet this need, we are developing a suite of engineering tools that can be deployed within the microbiome to carry out specific functions, at designated times, and in predetermined locales. At the same time, we are utilizing genetic engineering approaches to achieve higher specificity in our understanding of host-microbe interactions by getting down to mechanism. Rather than current options for broad-range antibiotics and 'everything but the kitchen sink' fecal transplants, we aim to develop a suite of refined, noninvasive synthetic therapeutic alternatives.
THAT GOES GLOBAL
The microbiomes of populations living in developing world nations are categorically different than those found in Westernized countries. This is unsurprising given differences in exposure. But what do these different microbiomes mean to individual health? In collaboration with partners around the globe, we are exploring how microbiome composition impacts inflammation, nutrition and infection. With a cross-cultural perspective, we aim to distill common factors driving disease and also determine whether microbiome-based therapies will be effective across the range of microbiomes and local contexts in which they are administered. Additionally, we have the goal of broadening participation in microbiome research worldwide.