Harnessing Nature’s DNA Delivery Devices for Microbiome Editing
A major barrier to in situ microbiome editing is lack of effective DNA delivery modalities, and improved delivery systems are needed to achieve editing in diverse taxa. Ideal delivery systems include natural mobile genetic elements (MGEs) such as bacteriophages that are generally highly selective for strains or species, as well as broad host-range self-transmissible plasmids that have evolved to efficiently transfer genetic material between distinct microbial species, even across phyla. However, only a small fraction of these systems have been commandeered as synthetic vectors. Our lab aims to engineer and repurpose wild bacteriophages and plasmids as DNA delivery devices to control microbial community members and ultimately to modify community function.
Shedding Light on the Genetic Dark Matter of Bacteriophage Genomes
Phages have evolved to be gene delivery machines with unparalleled efficiency and specificity and thus represent ideal systems for delivery of custom genetic cargo to target bacteria within microbial communities. However, engineering bacteriophages for DNA delivery requires an understanding of their genetic content, or at a minimum which genes are essential for generation of phage particles that infect a target organism. Our lab has developed next-generation phage functional genomics technologies that we are applying to identify essential phage genes and probe phage gene functions in high throughput. This work will allow us to rapidly redesign and customize natural bacteriophages as DNA delivery devices, while simultaneously uncovering phage-encoded fitness determinants across a wide range of conditions and hosts.
Microbes exist in the context of microbial communities, whose collective functions impact human health and wellbeing directly through interactions with our bodies and indirectly through production of potent greenhouse gasses that contribute to climate change. Our lab is developing genome editing technologies to study microbial communities and control their collective behaviors. We are applying these tools in:
livestock rumen microbiomes to reduce methane emissions and to engineer designer communities that can convert recalcitrant carbon sources into valuable products
human gut microbiomes to study the microbial genetic basis of microbiome-associated diseases and to develop microbiome editing-based therapeutic interventions