Recent advances in our understanding of tuberculosis infection demonstrate that infection within a given individual is highly heterogeneous; however, the determinants that drive lesions towards complete bacterial sterilization remain poorly understood. We are interested in developing new tools to dissect the complex dynamics of bacterial infection at a variety of scales ranging from single cells to infected hosts sitting in both “reference frames” by taking both an immunologist’s and a microbiologist’s perspective. Combining new technologies with classical approaches, we are focused ultimately on the goal to manipulate the immune system to improve bacterial control.
Our research revolves around two motivating questions –
1. What macrophage processes contribute to effective bacterial killing and what are the bacterial evasion mechanisms to resist such stress?
2. How can manipulate macrophage plasticity and program macrophage function in homeostasis and disease?
To this end, we are pursuing several projects aimed at both answering these question directly and developing new tools to further our understanding of these complex bacterium
:hostprotein :proteininteractions using genetically-encoded methods of extracting complexes
Novel single-cell algorithms to analyze datasets across diverse methods and samplesBrian Hie
Multiplexed, pooled infections for interrogating strain-based heterogeneity among host cell populationsJosh Peters
Macrophage plasticity and commitment in response to differentiation cues and cytokinesChris Itoh, Brian Hie, Josh Peters
Host-modulating bacterial factors and impact on host heterogeneityJosh Peters
Host-directed agents to manipulate macrophage state in favor of bacterial control