OUR RESEARCH
BACTERIAL ADAPTATION IN THE HOST
How pathogens sense, survive and evade the immune pressures they encounter during infection
BACTERIAL ADAPTATION IN THE HOST
Bacteria experience the host as a complex and often hostile environment. Inside immune cells, they encounter antimicrobial peptides, reactive oxygen and nitrogen species, nutrient limitation and rapidly changing cellular conditions. Successful pathogens sense these pressures and reprogram their gene expression, metabolism and cellular physiology
We use Salmonella to understand how immune chemistry shapes bacterial behaviour inside host cells. Our research examines the stress-response pathways, regulatory networks and virulence programs that allow bacteria to survive, replicate and evade innate immunity. We are particularly interested in how regulatory evolution generates new disease-associated traits.
Our work combines intracellular transcriptomics, microbiology, imaging and experimental models of infection. By determining what bacteria are actually doing inside the host, we uncover fundamental principles of pathogenesis and identify adaptations that may become targets for new therapies.
NEW THERAPIES FOR DRUG-RESISTANT INFECTIONS
Discoverying antibiotics, combinations therapies, and host-directed therapeutics
NEW THERAPIES FOR DRUG-RESISTANT INFECTIONS
Many antibiotics are discovered and tested under laboratory conditions that bear little resemblance to the environments bacteria experience during infection. We take a different approach by recreating host-relevant conditions and searching for therapeutic vulnerabilities that emerge only when pathogens confront immune and chemical pressures.
Using high-throughput screening, chemical biology, cell-based infection models and phenotypic profiling, we discover compounds that kill bacteria, increase the activity of existing antibiotics or strengthen the antimicrobial functions of host immune cells. Our work includes direct-acting antibiotics, antibiotic potentiators, dose-sparing combination therapies and host-directed therapeutics.
Our goal is to turn discoveries about infection biology into practical therapeutic strategies for invasive Salmonella and other difficult-to-treat bacterial infections.
MICROBIAL DRIVERS OF CROHN'S DISEASE
Understading how gut bacteria persist, expand and contribute to chronic intestinal inflammation
Crohn’s disease arises through complex interactions between host susceptibility, the intestinal microbiota and environmental exposures. Although no single microorganism causes Crohn’s disease, particular bacteria can exploit a susceptible intestinal environment and contribute to persistent inflammation.
Our research focuses on adherent-invasive Escherichia coli, or AIEC, a group of bacteria associated with Crohn’s disease. AIEC can colonize intestinal tissues, survive within macrophages and acquire traits that allow them to persist in individual hosts. We investigate how bacterial virulence, host immune responses, microbial communities and environmental disturbances such as antibiotics, gastrointestinal infections, and stress combine to promote AIEC expansion and disease.
Using cellular and preclinical models, genomics, microbial ecology and quantitative infection biology, we seek to define the contribution of AIEC to Crohn’s disease and develop more precise ways to control harmful microbes without broadly disrupting the intestinal microbiota.