LABORATORY OF INTRACELLULAR BACTERIA & HOST INTERACTIONS

University of Washington

overview_banner.jpg

Our Research

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

Functional genetics

 

Chlamydia–host proteomics

extrusion_banner.jpg
 

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.

sequence_banner.jpg

Functional Genetics

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

WikiGenomes: an open web application for community consumption and curation of gene annotation data in Wikidata

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. 

Version 1.0

C. trachomatis D  PDF
C. trachomatis L2  PDF
C. muridarum Nigg  PDF
3 genomes stacked  PDF

proteomics_banner.jpg

Chlamydia–host proteomics

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

 

Featured papers

 

Chlamydia trachomatis cellular exit alters interactions with host dendritic cells
Sherrid AM & Hybiske K
Infect Immun (2017)
PubMed | Journal

Extrusions are phagocytosed and promote Chlamydia survival within macrophages
Zuck M, Ellis T, Venida A, Hybiske K
Cell Microbiol (2017)
PubMed | Journal

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
Immunity (2017)
PubMed | Journal

Conservation of extrusion as an exit mechanism for Chlamydia
Zuck M, Sherrid A, Suchland R, Ellis T, Hybiske K
Pathog Dis (2016)
PubMed | Journal

Using fluorescent proteins to visualize and quantitate Chlamydia vacuole growth dynamics in living cells
Zuck M, Feng C, Hybiske K
J Vis Exp (2015)
PubMed | Journal

Expanding the molecular toolkit for Chlamydia
Hybiske K
Cell Host Microbe (2015)
PubMed | Journal

Developmental stage oxidoreductive states of Chlamydia and infected host cells
Wang X, Schwarzer C, Hybiske K, Machen TE, Stephens RS
mBio (2014)
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

Exit strategies of intracellular pathogens
Hybiske K & Stephens RS
Nature Rev Microbiol (2008)
PubMed | Journal

Mechanisms of host cell exit by the intracellular bacterium Chlamydia
Hybiske K & Stephens RS
Proc Natl Acad Sci USA (2007)
PubMed | Journal


Go to PubMed for a full list of laboratory publications

Current Lab Members

Kevin Hybiske, PhD Assistant Professor Department of Medicine University of Washington  

Kevin Hybiske, PhD
Assistant Professor
Department of Medicine
University of Washington

 

Yibing Wang, PhD Research Scientist

Yibing Wang, PhD
Research Scientist

Meghan Zuck Infectious Diseases & Immunity Graduate Student

Meghan Zuck
Infectious Diseases & Immunity Graduate Student

Mary Dickinson Pathobiology Graduate Student

Mary Dickinson
Pathobiology Graduate Student

Bob Suchland Research Scientist

Bob Suchland
Research Scientist

Elaina Marie Milton Microbiology Undergraduate

Elaina Marie Milton
Microbiology Undergraduate

Forrest Kwong Cellular and Molecular Biology Undergraduate

Forrest Kwong
Cellular and Molecular Biology Undergraduate

Allie Casper Undergraduate

Allie Casper
Undergraduate

Lab Alumni

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.

Address

750 Republican Street
Seattle, WA, 98109
United States

 

Contact

khybiske[at]uw.edu
206-616-1549

 

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.

UNDERGRADUATE STUDENTS

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.