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Research Interests

To survive in eukaryotic cells, intracellular bacteria have evolved complex mechanisms that maintain the delicate balance between exploiting and preserving host cellular resources. Our group investigates the cellular and molecular mechanisms that bacterial pathogens use to survive and replicate inside host cells. Our model system is听Legionella pneumophila, a Gram negative bacterium commonly found as an endosymbiont of amoebae in fresh water and soil.听L. pneumophila听is also an opportunistic pathogen and infects human alveolar macrophages upon inhalation of contaminated aerosols causing a severe form of pneumonia known as Legionnaires' disease.听L. pneumophila听is internalized into host cells by phagocytosis and remains enclosed in a membrane-bound compartment that the pathogen 鈥渞emodels鈥� in order to escape degradation by the host and support bacterial growth. Over the course of infection,听L. pneumophila听translocates more than 300 effector proteins into the host cytosol through a specialized secretion system. These effectors manipulate host proteins to subvert eukaryotic cellular pathways. We use a multifaceted approach involving biochemistry, cell biology, and genetics to study two important aspects of infectious disease: eukaryotic pathways targeted during infection and mechanisms that bacterial proteins use to modulate the activity of host proteins.

Current Projects

Both amoebae and macrophages are phagocytic cells and they engulf and destroy microorganisms. Under normal circumstances, the phagosome containing the cargo destined for degradation undergoes maturation through sequential fusion with endocytic compartments and ultimately with the lysosome to destroy its contents. However,听听L. pneumophila听resists degradation in both cell types by blocking phagosome maturation. A current focus in our lab is to determine how听L. pneumophila听modulates membrane transport pathways of the host cell to derail phagosome maturation.

A striking feature of听L. pneumophila听is its ability to translocate a vast number of effector proteins into the host cell to subvert the function of key regulatory proteins including Rab GTPases. These proteins act as molecular switches and they are attractive targets for intracellular bacterial pathogens due to the pivotal roles they play in eukaryotic cell function. Rab GTPases are targeted by听L. pneumophila听effector proteins during infection and our group is pursuing the mechanisms that听L. pneumophila听uses to manipulate their activity. We focus on determining how听L. pneumophila听effector proteins control the activity of host small GTPases through post-translational modifications.听

Research Group

Graduate students

• Samual Allgood (doctoral)
• Rebecca Noll (doctoral)
• Colleen Pike (doctoral)
• Barbara Romero-Due帽as (doctoral)
  

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Undergraduate students

• Andre Cunningham
• Matthew Bott