Novel Sensory Regulators of Immunity
Macrophages are a type of immune cell that can be found in every organ of the human body, even in the absence of infection and inflammation. These cells function as a type of security system, becoming quickly activated upon the detection of pathogens to coordinate an appropriate response. Interestingly, these cells also detect deviations from particular homeostatic parameters, such as pH, temperature, and nutrient availability. Because these parameters are altered during infections and tumorigenesis, the macrophage can also become activated when these environmental attributes are altered, avoiding the need to directly sense pathogen and allowing the host to mount a faster immune response. In our lab, we try to understand what homeostatic parameters are capable of macrophage monitoring, and how the macrophage regulates and tailors its immune response with regards to these environmental factors.
Novel Genetic Functions of the Mammalian Microbiome
Within any individual human, there are at least as many bacterial cells as there are human cells. Dauntingly, there are at least 10x more bacterial genes compared to human genes. Although it is well appreciated that the collection of bacteria in a human (referred to as the microbiome) are capable of driving human disease, the precise mechanisms are poorly understood. One approach is to look at the genetic products expressed by the microbiome to try and understand pathogenesis of human disease. However, most microbial gene functions are only ascribed based on predictive models, rather than biochemical verifications. We aim to study microbial genes using a gain-of-function screening approach. Our system is capable of enriching for novel genetic products that are directly relevant in proper bacterial adaptation to the mammalian intestine, as well as creating an environment that can sustain pathological inflammation and disease.