John S. “Sandy” Parkinson is a molecular biologist/geneticist, currently a distinguished professor at the University of Utah. He is known for his research on bacterial chemotaxis, the signaling system that allows motile bacteria such as Escherichia coli to detect and respond to chemical changes in their environment. His work has defined the protein components and molecular mechanisms of chemotaxis signaling, and has informed the broader understanding of two component regulatory systems used throughout the bacterial world.
Education Parkinson received an A.B. in Biology from Haverford College in 1965, and a Ph.D. in genetics and biophysics from the California Institute of Technology in 1969. He carried out postdoctoral research with Julius Adler at the University of Wisconsin–Madison from 1970–72, where he began the mutational analysis of E-coli chemotaxis that would define his subsequent career.
Career Parkinson joined the Biology Department at the University of Utah in 1972 as an Assistant Professor. He served as Director of the university's Molecular Biology Program (1990–1992) and Microbial Biology Program (2002–2013) and as Chair of the Biology Department (1996-2001). In 2009 he was named a Distinguished Professor in the School of Biological Sciences at the University of Utah.
Scientific contributions
E. coli chemotaxis mutants Bacteria rely on two principal types of stimulus-response systems: two-component signaling pathways that mediate changes in gene expression, and chemotaxis signaling pathways that control locomotor behavior. Parkinson's laboratory carried out early genetic studies of E-coli chemotaxis that identified the protein components of the chemotaxis signaling pathway, defined their functions, and established how they communicate with one another, producing a comprehensive picture of the “wiring diagram” of the chemotaxis circuitry.
This work also described the signaling properties of communication modules with which bacteria assemble their broader array of two-component signaling pathways, insights that paved the way for subsequent molecular analyses of the underlying signaling mechanisms. Parkinson's group has developed and freely disseminated bacterial strains and plasmids to hundreds of laboratories worldwide for research on chemotaxis and motility in various microbes.
Chemoreceptor signaling complexes In motile bacteria and archaea, chemoreceptors known as methyl-accepting chemotaxis proteins (MCPs) convert information about external attractant and repellent levels into signals that control locomotor behavior. The extensively studied MCPs of E-coli serve as important models for understanding transmembrane and intracellular signal transduction. Parkinson's molecular studies of E-coli MCPs showed that the cytoplasmic tips of receptor molecules form stable complexes with one another, with a signaling autokinase, CheA, and with a scaffolding protein, CheW, that couples CheA activity to receptor control.
His group showed that receptors of different detection specificities signal collaboratively within a mixed trimer, allowing integration of stimulus inputs.
More recently, in collaboration with Ady Vaknin's group at the Hebrew University in Jerusalem, Parkinson's laboratory identified an interface between the CheA and CheW proteins that links receptor core complexes into a signaling array that operates like a highly cooperative, multi subunit, allosteric enzyme. Amino acid replacements in CheA or CheW that disrupt this key interface dissipate receptor arrays into individual signaling complexes, that detect and respond to chemoeffectors but with little or no cooperativity.
HAMP domain signaling mechanisms Transmembrane chemoreceptors and sensor kinases typically contain a HAMP domain in the membrane-proximal portion of their cytoplasmic signaling domain. HAMP domains comprise four-helix bundle signaling elements that mediate input-output transactions in many microbial signaling proteins. Parkinson's group carried out extensive mutational analyses of the HAMP domain in Tsr, the E-coli serine chemoreceptor, leading to a new signaling paradigm with likely widespread relevance to biological signal transduction mechanisms. That work found that HAMP domains are not discrete two-state signaling devices, but rather most likely operate over a range of essentially isoenergetic conformations. In this “dynamic-bundle” model, input signals are proposed to shift the HAMP conformational landscape, which in turn governs the conformation and dynamic behavior of the chemoreceptor tip to elicit output responses. These studies contributed to an emerging conceptual framework in which highly sensitive chemoreceptor molecules, such as those of bacteria, contain serially connected signaling elements whose structural interactions are dynamically poised to respond to low-energy ligand binding events, a strategy that may prove to underlie sensory transduction systems more broadly across organisms.
Awards and Honors
1992-2001 – NIH MERIT award. 1996 – Chair, Gordon Research Conference on Sensory Transduction in Microorganisms. 1996 – elected fellow, American Academy of Microbiology. 1999 – University of Utah's Distinguished Research Award. 1999-2005 – member, Editorial Board, Journal of Bacteriology. 2006-2015 – Editor, Journal of Bacteriology. 2019 – elected fellow, American Association for the Advancement of Science.
Research Parkinson studies bacterial chemotaxis, particularly the chemotactic behavior of E-coli to elucidate the molecular mechanisms that cells use to detect and process information about their chemical environment. Parkinson began mutational analysis of E-coli chemotaxis as a postdoctoral student with Julius Adler in 1970. As an independent investigator, Parkinson became the primary source of mutant strains, generously making available his vast strain collection and his knowledge and thus enhancing the collective progress of the field.
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