Overview
Bacteria are everywhere, and their interactions with each other, their hosts, and their environment have powerful consequences. We study these interactions to discover key factors mediating cellular responses and to enable engineering of bacteria for the targeted delivery of beneficial proteins and nucleic acids. Our work is focused on two complimentary areas:
Precision Bacterial Control
Bacteria cause major disease burdens and provide opportunities for precise microbiome control. Our group addresses the central challenge of selectively eliminating harmful bacteria while preserving beneficial microbes by harnessing microcins, a hidden family of narrow-spectrum antibacterials used in bacterial competition. These naturally evolved molecules achieve family- to species-level specificity minimizing collateral damage and bypassing existing antibiotic resistance. We develop computational and experimental approaches to uncover and characterize the hidden diversity of microcins and leverage our discoveries to engineer probiotics that deliver microcins in vivo, enabling targeted control of gut pathogens, microbiome members linked to disease, and plant pathogens in agriculture. In parallel, we are using microcin entry mechanisms to inspire synthetic antibiotics, building a new framework for precision bacterial control across human, animal, and environmental settings.
Bacteria-Directed Host Responses
Cell-based therapies empower the treatment of previously intractable diseases. Bacteria offer an under explored avenue for expanding this concept into uncharted realms of host engagement. Our group is pursuing bacteria to direct host responses through two complementary strategies.
i) We are developing tools for bacteria production of eukaryotic signaling factors to allow direct and programmable modulation of host cell responses. This work relies on our advancement of systems for bacterial protein secretion and display. These platforms also provide opportunities for high-throughput analysis of otherwise inaccessible proteins and to generate datasets that accelerate computational approaches for protein discovery and design.
ii) Bacteria share genetic materials through horizontal gene transfer. We are building bacterial genetic delivery vectors to extend this process and allow targeted transport of nucleic acid therapeutics to eukaryotic cells. By using bacteria as both production and delivery systems, this approach allows for simplified transport of larger, multiple therapeutic payloads through several delivery routes.
By leveraging mechanisms of protein secretion, surface display, and gene transfer we are designing bacteria to influence infection outcomes, reshape microbiomes, regulate immune responses, and enhance agricultural resilience.
