Microbiology / Immunology

Our long-term objective is to understand the cellular and molecular events involved in tumor-induced immune suppression by macrophages. We have been actively pursuing this fact using a murine tumor model and have previously documented that tumor growth is associated with a decrease in immune function caused by a downregulation of positive regulatory factors and an increase in negative regulatory factors.

Molecular Ecology of Mycobacterium avium: M. avium is an opportunistic pathogen that is present in natural and drinking waters. Current research is focused on identifying the genes that are responsible for: growth in natural and drinking waters, disinfectant and antibiotic resistance, intracellular growth in protozoa and amoeba, and intracellular growth in human and animal macrophages.

Identification of Novel Antibiotics: The laboratory has collected a variety of microorganisms that have broad spectrum antimicrobial activity. Previous work led to development of a variety of rapid methods for detecting and measuring antimicrobial activity. Current objectives are to clone genes involved in antibiotic production and improve antibiotic yields by fermentation.

Innate immune response is our first line of defense against diverse microbial pathogens.  In addition, innate immunity regulates various inflammatory processes.  Alteration/aberration in innate immunity contributes to human diseases ranging from infection to atherosclerosis, diabetes and cancer.  Our research program aims to characterize the molecular and cellular signaling events controlling innate immunity response.  Several key molecules including interleukin-1 receptor associated kinases (IRAKs) are involved in innate immunity regulation.  1) We are examining the biochemical processes controlling IRAKs’ modification, intra-cellular translocation and activation;  2) We are determining the downstream function of IRAK proteins;  3) We are studying the contribution of IRAKs to the pathogenesis of atherosclerosis and cancer using transgenic mice model.

Current Research: (1) The interactions of the host immune system with the anaerobic bacterial pathogen Clostridium perfringens. Specifically, the molecular mechanisms that allow the bacteria to avoid being killed by phagocytic cells of the immune system, macrophages and neutrophils. (2) The molecular regulation of toxin synthesis by C. perfringens, especially the enterotoxin that is responsible for food poisoning outbreaks.

Our lab works on two main projects: (1) Synthesis of the cell wall within bacterial spores. This wall is a major determinant of the stability of spores and a target for development of anti-bioterrorism agents effective against Anthrax spores. (2) Synthesis of the vegetative cell wall in Gram positive bacteria. Peptidoglycan synthesis determines cell shape and division frequency. Research is designed to identify potential new antibiotic targets.

Scharf Lab - Dr. Birgit Scharf (email)

The research in our laboratory is focused on bacterial motility and chemotaxis using the nitrogen-fixing plant symbiont Sinorhizobium meliloti as model organism. Chemotaxis is based on perception and processing of environmental information by receptors and signal transduction via a two-component-system to the flagellar motor. The molecular mechanisms of swimming, chemoreception, and signal transduction differ from the enterobacterial pardigm. The S. meliloti chemotaxis system utilizes two response regulator proteins, CheY1 and CheY2, but lacks a specific phosphatase. CheY2-P is the dominant regulator of motor response. Its dephosphorylation involves retro-phosphorylation back to the kinase CheA, which in turn phosphorylates free CheY1. S. meliloti exhibits a different type of flagella rotation and hence, swimming mode. While the E. coli motor causes a change of swimming direction by a switch from counter-clockwise to clockwise rotation, the S. meliloti motor rotates exclusively clockwise, but can vary its rotational speed. Changes in the swimming path are caused by an asynchronous deceleration of individual flagella filaments. Rotary speed variation has its molecular corollary in two new motility proteins, MotC and MotE.

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Florian Schubot lab - fschubot@vt.edu

Regulatory Mechanisms that govern expression of Type III Secretion systems in gram-negative bacterial pathogens

Some of the most potent pathogens utilize type III secretion systems: Yersinia pestis, enteropathogenic E.coli, Shigella flexneri, Salmonella enterica, and Pseudomonas aeruginosa. Since disruption of the type III secretion apparatus invariably leads to a significant attenuation of virulence, the structural and functional components of the secretion machinery are considered high value drug targets. Rather than targeting individual components of secretion machinery we have decided to focus our efforts on achieving a broader impact by suppressing the regulatory cascades that activate expression of multiple type III secretion-related genes.
The research in my laboratory is best described as structural microbiology. By way of protein crystallography in conjunction with microbiology we aim to decipher the molecular basis for virulence of bacterial pathogens. The gained insights will be applied towards reaching our ultimate goal: the structure-based development of potent antimicrobial agents.

Our lab studies environmental sensing and control of gene expression in bacteria. Current projects involve (1) the genetics, molecular biology and biochemistry of regulatory factors involved in the mechanism of bacterial cell density-dependent gene regulation known as quorum sensing; (2) analysis of transcription initiation in the anaerobic human pathogen Bacteroides; and (3) studies of microbial populations in environmental samples using molecular techniques.

Our lab uses contemporary tools in biology to address questions in two areas: 1) bacterial inter- and intra-cellular signal transduction involved in bacterial motility and developmental biology. The fundamental question is how bacterial cells perceive changes in their environment and properly response to such changes both individually and collectively. 2) Structural basis and mechanisms of type IV pilus (TFP) functions. The ability of TFP to retract is essential for bacterial surface motility, pathogenesis and biofilm formation. We attempt to understand both the “basal” structure of TFP and mechanisms of TFP retraction.