Overview
Bacteria are everywhere, and their interactions with each other, their hosts, and their environment have powerful consequences. We study these interactions and engineer bacteria capable of effecting them to prevent and treat disease. Our work focuses on two complimentary areas:
Designed Bacterial Control
Bacteria cause infections in human, animals, and plants but they also provide essential benefits to each host. We address the central challenge of eliminating harmful bacteria while preserving beneficial microbes by harnessing microcins, a hidden family of narrow-spectrum antibacterials used in bacterial competition. Microcins can achieve family- to species-level specificity, minimizing collateral damage to commensal microbes and circumventing existing antibiotic resistance mechanisms. We combine computational discovery with experimental characterization to map microcin diversity and define their activity, specificity, and mechanisms of action. We leverage this knowledge and engineer probiotic bacteria to deliver microcins directly within relevant host environments, enabling targeted pathogen control. In parallel, we use insights into microcin entry mechanisms to guide the design of synthetic antibiotics. Together, our efforts establish a framework for precision bacterial control across human, animal, and environmental systems.
Bacteria-Directed Host Responses
Cell-based therapies have transformed the treatment of diseases once considered intractable. Bacteria represent an underexplored but powerful platform for extending this concept into new modes of host engagement. We are pursing this idea through two complementary strategies.
i) We are engineering bacteria that mimic eukaryotic protein signaling pathways and thereby direct host-cell behavior. We are primarily focused on directing immune responses.This work builds on our advancements in protein-secretion and surface-display that are allowing bacteria to make, display and release complex eukaryotic proteins. We leverage these abilities to engineer bacteria that selectively engage with our immune system and drive desired host responses.
ii) In a complimentary approach we are using bacteria to reprogram eukaryotic cells with new functions. To do so we are building bacterial nucleic acid delivery systems to safely transport genes 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 harnessing bacterial protein secretion, surface display, and gene-transfer mechanisms, we aim to engineer living bacterial systems that influence infection outcomes, reshape microbiomes, regulate immune responses, and strengthen agricultural resilience.
