Biography

Cell biology approach to study host-pathogen interactions

Intracellular bacteria live and survive inside host cells, using the host cell’s own metabolism as a source of nutrients. An intracellular lifestyle also provides a safe replicative niche for the bacteria. To accomplish this feat, intracellular bacteria secrete numerous bacterial proteins, called effectors. These effectors alter the host cell biology to block the cell’s innate immune response and to facilitate the progression of the bacteria’s developmental cycle.

The lab focuses on understanding the molecular function of these bacterial effectors to better understand how intracellular bacteria invade and survive within the host cell. To do this, we developed a unique approach—we use the model organism Drosophila melanogaster (fruit flies) as an in vivo cell biology platform to study transgenically expressed effectors, either singly or in combination. Transgenic expression of effectors allows for the isolated study of effector function without the confounding effects of infection. The well-understood cell and developmental biology of fruit flies greatly aids in the identification of impacted cell processes and signaling pathways—a great tool to have for discovery of novel function. Finally, the wealth of genetic tools, reagents, and approaches available to Drosophila researchers enables detailed genetic and mechanistic studies.

We are currently working on effectors secreted by the intracellular pathogen Chlamydia. Chlamydia trachomatis is the leading cause of bacterial sexually-transmitted infection (STI) in the United States, while other Chlamydia or Chlamydia-related species evolved to infect a wide range of hosts in the animal kingdom—including other mammals, birds, reptiles, and fish. Chlamydia secretes numerous effectors at every stage of its developmental cycle, majority of which are poorly understood. We are creating transgenic Drosophila that can express effectors that are important for different stages of Chlamydia development but whose molecular function is unknown or poorly understood. Our goal is to discover the molecular function of these effectors to improve the overall understanding of the molecular strategy of Chlamydia infection. In the future, we will expand our approach to study effectors of other intracellular bacteria to better appreciate the common as well as different strategies that these bacterial specialists employ.

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