Mechanisms of Chlamydia Pathogenesis
Our research focus is to solve how the major human pathogen Chlamydia manipulates host cell function in order to cause infectious disease. We apply a diverse array of genetic, cellular, and molecular techniques to reveal the underlying mechanisms of pathogenesis for these highly successful bacteria.
Chlamydia exit from host cells
The great escape
extrusion strategy of chlamydia exit
Intracellular pathogens have evolved numerous strategies for promoting their exit from host cells, consistent with the essential role of exit for pathogenesis. Yet despite this fundamental importance, microbial exit largely remains an unexplored research area. Efforts in our lab aim to advance understanding of this new theme.
Our pioneering discoveries forged the current understanding of Chlamydia exit from host cells. Chlamydiae possess two mechanisms for accomplishing cellular escape that are mutually exclusive: extrusion and lysis. Extrusion is a packaged release of Chlamydia in which the bacteria are pinched off from the host cell into a membrane-encased compartment, a process that leaves the original host cell intact. Extrusions are novel structures that enhance the biology of Chlamydia infection in many fascinating ways, such as serving as a ‘stealth shuttle’ as these bacteria attempt to elude the host immune system.
Discovery of Chlamydia virulence factors
Genome-wide discovery and characterization of virulence determinants for Chlamydia remains a major unaddressed research area. Through recent landmark advances in genetic manipulation of Chlamydia, and a rich collaboration with Scott Hefty and Dan Rockey that exploits new methodologies for genetic engineering in Chlamydia, we are working to discover the Chlamydia genes and host protein targets that play critical roles in Chlamydia infection and pathogenesis.
Transposon mutants generated through this work will be made available to the field, and will be first annotated in Chlambase.org.
Papers coming soon
Chlamydia genome reannotation project ~ wikigenomes
We are working with the Su Lab, experts in aggregating community acquired research knowledge into open source databases, to develop and launch Chlambase.org (name subject to change). Chlambase is a fork of WikiGenomes.org, a Wikidata-backed database of over 100 NCBI microbial reference genomes. The goal of Chlambase is to create a streamlined, researcher-curated database of genetic and proteomic knowledge for the Chlamydia research community. This database uniquely offers information not available on other services, such as:
- Current gene annotations
- Orthologous gene comparisons
- Annotations of Chlamydia mutants (SNV, transposon, group II intron)
- Developmental expression timing
- RB/EB expression
- Host protein interactions
Version 1.0 launch is scheduled for Fall 2017
Chlamydia genome posters
Chlamydiae possess streamlined and highly conserved genomes. These genomes contain valuable information that guides Chlamydia research throughout the world. As part of our ongoing efforts to perform functional genomics on Chlamydia species, on a genome-wide scale, we have built updated annotated genome maps for C. trachomatis D, C. trachomatis L2, and C. muridarum Nigg. (We also like making posters). Genes are color-coded based on their functional category, and organized into predicted operons.
Get your own copy
Click the links below to download a 35 x 23 in poster copy of your choosing. Send to your local printing service to make your own poster. Alternative file formats available upon request.
combining genetics & proteomics to illuminate novel chlamydia-host interactions
Successful infection of host cells by Chlamydia requires continuous interactions between scores of bacteria and host proteins, in a manner that ultimately benefits the pathogen. Identification and characterization of these protein interactions is a high priority research area, and may spearhead the development of novel antimicrobials.
We are developing and exploiting novel proteomic systems to probe unique interactions between intracellular Chlamydia and host cell targets.
Papers coming soon
Sensing of bacterial cyclic dinucleotides by the oxidoreductase RECON promotes NF-kB activation and shapes a proinflammatory antibacterial states
McFarland AP, Luo S, Ahmed-Qadri F, Zuck M, Thayer EF, Goo YA, Hybiske K, Tong L, Woodward JJ
PubMed | Journal
Actin recruitment to the Chlamydia inclusion is spatiotemporally regulated by a mechanism that requires host and bacterial factors
Chin E, Kirker K, Zuck M, James G, Hybiske K
PLoS One (2012)
PubMed | Journal
Go to PubMed for a full list of laboratory publications
Current Lab Members
Ashley Sherrid, Postdoctoral fellow (University of Washington)
Amy Lee, Undergraduate (University of Washington)
Jessica Cooper, Undergraduate (University of Washington)
Kathy Tuan, Undergraduate (University of Washington)
Mason Bliss, Undergraduate (University of Washington)
Melissa Chan (University of Washington)
Tisha Ellis, Postdoctoral fellow (University of Washington)
Rebecca Peters, Undergraduate (University of Washington)
Erin Bryar, Undergraduate (University of Washington)
Tom Ilustrisimo, Research Associate (UC Berkeley)
Caroline Feng, Research Associate (UC Berkeley)
Desiree Albano, Undergraduate (UC Berkeley)
Elizabeth Chin, Undergraduate (UC Berkeley)
Christina Adams, Undergraduate, UC Berkeley Amgen Scholars Program
Yurika Hara, Undergraduate (UC Berkeley)
Anthony Venida, Undergraduate, UC Berkeley Amgen Scholars Program
The Hybiske Lab is located at the UW Medicine – South Lake Union research cluster, situated near picturesque Lake Union, the Space Needle, the Center for Infectious Disease Research, the Allen Institute, Fred Hutch, and downtown Seattle.
750 Republican Street
Seattle, WA, 98109
Interested in Joining?
The Hybiske lab is always interested in hearing from innovative individuals: prospective graduate students, postdocs, fellows, and undergraduate students. We are part of an unparalleled nexus of interdepartmental research expertise in microbial pathogenesis, infectious diseases, and global health at the University of Washington. We also engage in collaborative interactions with the Center for Emerging and Reemerging Infectious Diseases (CERID), Global Health, Microbiology, the Center for AIDS and STD, the Center for Infectious Disease Research (CIDR), and the Center for Innate Immunity and Immune Disease (CIIID).
PROSPECTIVE GRADUATE STUDENTS
You must apply (and be accepted by) the Pathobiology PhD Program.
POSTDOCS AND FELLOWS
No current openings available.
UW students majoring in Microbiology or similar areas are encouraged to appy. Contact Kevin by email to inquire about possible openings. Please provide a copy of your current academic transcript, a resume, and a detailed statement of why you are a good fit for our possible needs.