The urgent need to combat antimicrobial resistance has driven renewed interest in antimicrobial peptides (AMPs) as novel therapeutic agents, yet their discovery and optimization remain challenging. Our research group leverages AI to revolutionize AMP discovery, focusing on the identification and enhancement of peptides from diverse microbial sources, such as the human oral microbiome. Using our AI-based, explainable deep learning model, EvoGradient, we predict AMP potency and virtually evolve peptide sequences to enhance their antimicrobial activity. We have successfully transformed weak AMPs into highly potent AMPs, with several demonstrating efficacy against multidrug-resistant clinical isolates of bacteria in vitro and in vivo. Continued advancements could enable rapid, automated AMP discovery pipelines, paving the way for precision antimicrobials tailored to combat resistant infections and address global health threats.
Metabolomics unlocks the chemical diversity of microbial systems, yet complex metabolomes and unannotated metabolites challenge comprehensive analysis. Our research group advances metabolomics analysis through innovative computational tools to decode intricate metabolic profiles, identifying novel natural products and uncharacterized metabolites. Our NP-PRESS pipeline uses MS1 and MS2 algorithms to filter interfering signals, revealing new bioactive compounds in microbial extracts, including those from extremophiles. Our AI-driven ComFaceID model predicts structural features from MS2 spectra, uncovering unique scaffolds with therapeutic potential. These tools promise to discover new bioactive molecules and map hidden metabolic pathways, transforming microbial chemistry exploration.
Living bacterial therapies have been proposed as an alternative approach to treating a broad array of cancers. Our research group advances this field by engineering live bacteria as self-sustaining therapeutic platforms to deliver anti-tumor agents directly within diseased tissues. We developed a novel system using genetically modified probiotic Escherichia coli, equipped with three genetic modules to autonomously produce light, photosensitizers, and oxygen, enabling self-driven photodynamic therapy for deep-seated tumors. This approach harnesses endogenous substrates to sustain prolonged therapeutic activity in vivo, eliciting robust anti-tumor immune responses. The potential to harness live bacteria as precision therapeutics could revolutionize cancer treatment and redefine biotherapeutic strategies.
