PhD

Curators Distinguished Professor Emeritus and Chair Emeritus

Biochemistry

Education

BS	Biology	Williams College	Williamstown, Mass.
MS	Biology	Case Western Reserve University	Cleveland, Ohio
PhD	Genetics	University of Wisconsin	Madison, Wis.

Research Area

Transmembrane receptors and sensory transduction in bacterial chemotaxis.

Research Description

The aim of our research is to elucidate molecular mechanisms of transmembrane receptors and sensory transduction. For more than 40 years our research group has provided important information about the transmembrane chemoreceptors and signaling complexes that mediate chemotaxis in Escherichia coli. We have helped make bacterial chemotaxis the best understood signaling system in biology and a favored subject for systems biology. Our experimental approaches combine biochemistry, biophysics and molecular genetics to investigate the “neurobiology” of bacteria.

We investigate processes by which receptors recognize ligand, signal across the membrane, produce intracellular signals, make supramolecular complexes, generate high sensitivity and wide dynamic range, integrate multiple signals, and mediate sensory adaptation. Elucidation of components and mechanisms involved in E. coli chemotaxis has wide impact because this sensory system is a paradigm for those systems that direct motility in the vast taxonomic range of microorganisms, many of which are biologically, medically and commercially important. In addition, bacterial chemotaxis is one of the best understood members of the superfamily of “two-component” signaling systems. Such two-component systems contain histidine kinases and phosphorylated response regulators that mediate responses to many environmental signals. They occur across much of the diversity of living things: most prokaryotes, many plants and some single-celled eukaryotes.

Recent projects in the laboratory include structural probing of receptor conformational changes in vivo and in vitro, characterization of receptor arrays in isolated membrane, determination of the relationship between supramolecular interactions and receptor function, definition of the core unit of chemotaxis signaling complexes and isolation of those core units as active complexes. Many of these projects have utilized Nanodiscs, an emerging technology for manipulation of membrane proteins in a water-soluble state. Our work often involves collaboration with leading laboratories in the application of biophysical, structural and modeling approaches to understanding complex biological systems. We will continue this multifaceted strategy of combining different approaches and disciplines. Members of our research group have the opportunity for training and experience in the entire range of these scientific areas.

Current areas of investigation include characterization of functional interactions among transmembrane receptors in supramolecular signaling complexes, identification of the conformational changes of transmembrane signaling by biophysical approaches including electron paramagnetic resonance (EPR) spectroscopy, determination of the three-dimensional structure of transmembrane chemoreceptors and their signaling complexes by structural electron microscopy, and crystallization of membrane bilayer-embedded chemoreceptors.

Notable Honors and Service

• Fellow, American Association for the Advancement of Science
• Fellow, American Academy of Microbiology
• MERIT Award NIH (2012-)
• University of Missouri Curators Distinguished Professorship (2012-)
• FASEB Board of Directors 2004-2008
• Protein Society, Secretary/Treasurer 2005-2008; Council member 2008-2009
• American Cancer Society Faculty Research Award, 1985-90
• McKnight Neuroscience Development Award, 1982-85
• Sloan Research Award in Neurosciences, 1973-75
• Editorial Boards
  • Protein Science (2008-2014)
  • The Journal of Microbiology (1995-2009)
  • Journal of Bacteriology (1976-93)
• Conference Organization
  • Chair, Gordon Conference on Sensory Transduction in Microorganisms; Vice-Chair 1990, Chair 1992
  • Organizer, 24th Steenbock Symposium: Behavior and Signaling in Microorganisms, 1995

Selected Publications

Stalla D, Akkaladevi N, White TA, Hazelbauer GL. (2019). Spatial Restrictions in Chemotaxis Signaling Arrays: A Role for Chemoreceptor Flexible Hinges across Bacterial Diversity. Int J Mol Sci. 20(12). doi: 10.3390/ijms20122989. [PubMed]

Mello BA, Pan W, Hazelbauer GL, Tu Y. (2018). A dual regulation mechanism of histidine kinase CheA identified by combining network-dynamics modeling and system-level input-output data. PLoS Comput Biol. 14(7):e1006305. doi: 10.1371/journal.pcbi.1006305. eCollection 2018 Jul. [PubMed]

Akkaladevi N, Bunyak F, Stalla D, White TA, Hazelbauer GL. (2018). Flexible Hinges in Bacterial Chemoreceptors. J Bacteriol. 200(5). doi: 10.1128/JB.00593-17. Print 2018 Mar 1. [PubMed]

Pan W, Dahlquist FW, Hazelbauer GL. (2017). Signaling complexes control the chemotaxis kinase by altering its apparent rate constant of autophosphorylation. Protein Sci. 26(8):1535-1546. doi: 10.1002/pro.3179. [PubMed]

Bartelli NL, Hazelbauer GL. (2016). Bacterial Chemoreceptor Dynamics: Helical Stability in the Cytoplasmic Domain Varies with Functional Segment and Adaptational Modification. J Mol Biol. 428(19):3789-804. doi: 10.1016/j.jmb.2016.06.005. [PubMed]

Bartelli NL, Hazelbauer GL. (2015). Differential backbone dynamics of companion helices in the extended helical coiled-coil domain of a bacterial chemoreceptor. Protein Sci. 24(11):1764-76. doi: 10.1002/pro.2767. [PubMed]

Parkinson JS, Hazelbauer GL, Falke JJ. (2015). Signaling and sensory adaptation in Escherichia coli chemoreceptors: 2015 update. Trends Microbiol. 23(5):257-66. doi: 10.1016/j.tim.2015.03.003. Review. [PubMed]

Li M, Hazelbauer GL. (2014). Selective allosteric coupling in core chemotaxis signaling complexes. Proc Natl Acad Sci U S A. 111(45):15940-5. doi: 10.1073/pnas.1415184111. [PubMed]

Amin DN, Hazelbauer GL. (2012). Influence of membrane lipid composition on a transmembrane bacterial chemoreceptor. J Biol Chem. 287(50):41697-705. doi: 10.1074/jbc.M112.415588. [PubMed]

Hazelbauer GL. (2012). Bacterial chemotaxis: the early years of molecular studies. Annu Rev Microbiol. 66:285-303. doi: 10.1146/annurev-micro-092611-150120. Review. [PubMed]

Current Funding

• NIH MERIT Award to 2022 (40 years of continuous NIH funding since 1982)