(Speaker Term: July 1, 2014 - June 30, 2016)
Michael J. Federle (term: 7/1/14 through 6/30/16)
Center for Pharmaceutical Biotechnology
University of Illinois at Chicago
3152 Molecular Biology Research Building
900 S. Ashland Avenue M/C 870
Chicago, IL 60607
Speaker’s Website: http://www.uic.edu/labs/federle/index.htm
ASM MEMBERSHIP AFFILIATION – Michael J. Federle
Primary Division: H (Genetics & Molecular Biology)
Secondary Division: B (Microbial Pathogens)
LECTURE TOPICS AND DESCRIPTIONS – Michael J. Federle
A New Regulatory System Facilitating Cell-to-Cell Signaling in Gram-positive Bacteria
The Federle lab has helped to discover a family of proteins and peptide pheromones that are widely-conserved among Gram-positive bacteria. The Rgg family of transcription factors is now known to directly bind short peptide signals that are imported to the cytoplasm and modulate gene expression. Investigations have focused on mechanisms of pheromone maturation, receptor-ligand interactions, transcriptional regulation, and Rgg protein biochemistry. The Rgg family is large and mechanisms of regulation are anticipated to vary with subclasses, but a clear understanding of responses of Rggs to peptides will assist in predicting gene expression responses.
Development of the Competent State in Non-transformable Species
All species of streptococcus contain a large, conserved set of genes facilitating competence for natural genetic transformation, yet a majority of these species have remained persistently refractory to genetic manipulation in the lab, and most have no reports of natural transformation. Discovery that the ComRS quorum-sensing pathway controls expression of the competence regulon in Pyogenic, Mutans, Salivarius, and Bovis species of streptococci offers an important step forward in understanding natural transformation in these bacteria. The Federle lab is focused on identifying the regulatory pathways that maintain tight control of this process, which likely contributes to the extraordinary genomic variability seen among pathogenic streptococci.
Interactions Between Pathogenic Streptococcal Species
At least two subgroups of Rgg proteins, exemplified by ComR and Rgg2/Rgg3 from S. pyogenes, are found to be highly conserved among different species of streptococci, and each utilizes nearly identical signaling pheromones. Since many of the species occupy similar niches in the human body, it is logical to ask if communication occurs between them, and if so, to what benefit. The Federle lab is currently investigating the consequences of interspecies interactions, focusing on biofilm development, natural transformation, and virulence factor expression.
Approaches to Identify Quorum Sensing Inhibitors
Since pheromone signaling has a clear effect on bacterial gene expression and behavior, the potential to influence behavior may be possible through manipulation of bacterial communication. The Federle lab has initiated high-throughput screening for molecules that block Rgg-pheromone signaling with compounds available in both chemical and genetic libraries. Candidate screening utilizes luciferase and fluorescence reporters together with robotic liquid handling, phage display, and flow cytometry. Initial results have found compounds that specifically and directly bind to Rgg proteins and that compete with pheromone binding.
BIOGRAPHICAL SKETCH – Michael J. Federle
Dr. Federle's ongoing research interests are in cell-cell communication among Gram-positive bacteria. His lab has helped identify a new class of quorum-sensing pathways that utilize proteins of the Rgg family and short, imported peptide pheromones. The lab’s work focuses on characterization of these pathways, identification of behaviors controlled by them, and development of small molecule probes into novel therapeutics aimed at interfering with bacterial communication to treat disease. Dr. Federle has been awarded an R01 grant from the NIH and was recently named a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease. He has been an invited speaker for more than 30 seminars and conferences and has authored 26 articles and book chapters. Dr. Federle serves on the editorial board for Journal of Bacteriology, and provides ad hoc reviews for mBio, Infection and Immunity, and Applied and Environmental Microbiology.
CV is available by request from firstname.lastname@example.org at ASM Headquarters
LECTURER’S PERSONAL STATEMENT – Michael J. Federle
I am particularly interested in serving as a lecturer for the opportunity to expand my understanding of broad topics in the field of microbiology, and to have the chance to bridge themes of microbiology by sharing my laboratory's work on intercellular communication. I believe the best opportunities for innovative ideas stem from discussions among individuals of diverse backgrounds and areas of expertise. It is my intuition that cell-cell signaling pathways, such as those studied in my lab, will have broad appeal to microbiologists in a variety of fields including bioengineering, cellular physiology and genetics, systems microbiology, microbiome structure, biofilm development, and pathogenesis and host-interactions. It is my intent to reach the interests of individuals in each of these fields to stimulate conversations that might result in seeing things from a new perspective. I sense that my talks reflect my enthusiasm and passion for microbiology, and that I may be able to provide some guidance to postdocs and students in regards to making the transition from mentored to independent research. One of my favorite things about having my own laboratory is the depth of interaction with students and postdocs and the chance to tap into their energy and optimism. I anticipate that ASM Branch Meetings are rich with young scientists eager to hear fresh ideas and develop new connections.