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THE BRITO LAB
RESEARCH
EXPOSING THE WORLD OF
HOST-MICROBIOME
PROTEIN-PROTEIN INTERACTIONS
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.
SYNTHETIC SOLUTIONS TO
TWEAK HOST-MICROBE
INTERACTIONS
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.
BACTERIAL EXTRACELLULAR VESICLES
INTERCEPTING TINY DISPATCHES
FROM THE MICROBIOME
Bacteria secrete packets full of proteins, lipids, small molecules and nucleic acids . We profilid these packets from members of the human gut microbiome.
ALGORITHMS THAT ACCELERATE
MICROBIOME DISCOVERY
Metagenomic data holds extremely rich information about the evolution of humans and their most intimately associated microbiota. We develop algorithms that squeeze as much information is possible from this data, from deconvolving strains, to identifying specific genetic elements associated with disease, to reconstructing phylogenies. We combine datatypes to push the scope of multi-omics analyses, improving proteomic pipelines to accommodate variants within the microbiome, modeling the movement of mobile genetic elements, and computationally extracting elements capable of producing certain metabolites without the need for genetic manipulation.
SOCIAL NETWORKS,
TRANSMISSION,
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.
MICROBIOME RESEARCH
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.