[Research Summary]
The major research efforts in the laboratory are directed towards understanding the molecular basis of pathogenesis of human infections caused by opportunistic gram-negative bacteria. The projects aim to better understand the molecular basis of regulation of expression of determinants of pathogenicity by the microorganisms, starting from signal perception and transmission, regulation of gene expression at the transcriptional and post-transcriptional levels and the targeting mechanisms of the virulence factors to their site of action. We have used Pseudomonas aeruginosa as a model opportunistic pathogen, because of its importance in infections of individuals with cystic fibrosis, patients with neutropenia, or those with serious burns and wounds. In each of these environments, the unique host-parasite relationship allows us to examination of a variety of bacterial factors that lead to colonization, persistence and resistance to host defenses.
The focus of the current work in the area of regulation is a broad attempt to define the complex signaling pathways and genetic regulatory networks, controlling virulence determinants. The areas investigated include the analyses of the functions of the various phosphorylation-based signaling pathways in assimilating and transmitting environmental cues leading to selective and controlled transcription specific genes encoding virulence factors. Recently discovered small regulatory RNAs, responsible for the post-transcriptional control of genes are also investigated in the lab. The lab has a major effort in determining the role of cyclic nucleotides in coordinating expression and function of factors involved in the formation of different polysaccharide matrices and secreted toxins that are major virulence determinants expressed by P. aeruginosa during chronic infections.
Another area of research in the laboratory focuses on studying the evolution of virulence traits in P. aeruginosa. We have identified several mobile elements, arranged in blocks of genes (so called genomic islands) that can move between bacteria, resulting in re-shaping of the genetic repertoire of individual recipient strains. The mechanisms and the consequences of this type of horizontal gene transfer, particularly if it leads to the acquisition of new virulence traits, will be analyzed in several infection models.
The major research efforts in the laboratory are directed towards understanding the molecular basis of pathogenesis of human infections caused by opportunistic gram-negative bacteria. The projects aim to better understand the molecular basis of regulation of expression of determinants of pathogenicity by the microorganisms, starting from signal perception and transmission, regulation of gene expression at the transcriptional and post-transcriptional levels and the targeting mechanisms of the virulence factors to their site of action. We have used Pseudomonas aeruginosa as a model opportunistic pathogen, because of its importance in infections of individuals with cystic fibrosis, patients with neutropenia, or those with serious burns and wounds. In each of these environments, the unique host-parasite relationship allows us to examination of a variety of bacterial factors that lead to colonization, persistence and resistance to host defenses.
The focus of the current work in the area of regulation is a broad attempt to define the complex signaling pathways and genetic regulatory networks, controlling virulence determinants. The areas investigated include the analyses of the functions of the various phosphorylation-based signaling pathways in assimilating and transmitting environmental cues leading to selective and controlled transcription specific genes encoding virulence factors. Recently discovered small regulatory RNAs, responsible for the post-transcriptional control of genes are also investigated in the lab. The lab has a major effort in determining the role of cyclic nucleotides in coordinating expression and function of factors involved in the formation of different polysaccharide matrices and secreted toxins that are major virulence determinants expressed by P. aeruginosa during chronic infections.
Another area of research in the laboratory focuses on studying the evolution of virulence traits in P. aeruginosa. We have identified several mobile elements, arranged in blocks of genes (so called genomic islands) that can move between bacteria, resulting in re-shaping of the genetic repertoire of individual recipient strains. The mechanisms and the consequences of this type of horizontal gene transfer, particularly if it leads to the acquisition of new virulence traits, will be analyzed in several infection models.
#Immunobiology #Microbiology
국가
미국
소속기관
Harvard medical school (학교)
연락처
책임자
Stephen Lory stephen_lory@hms.harvard.edu
