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RESEARCH INTERESTS
Circadian Rhythms in Prokaroytes
Bacterial Signal Transduction
Microbial Biology
PUBLICATIONS
Both the concept and the recognition of a circadian clock functioning within
a prokaryotic organism are new. (See Kondo, T., N.F. Tsinoremas, S.S. Golden,
C.H. Johnson, S. Kutsuna, and M. Ishiura. 1994. Circadian clock mutants of
cyanobacteria, Science 266:1233-1236.) Surrounding this novelty is a
scientific literature pertaining to circadian biology and biological oscillators
within
eukaryotic organisms that dates back nearly 300 years. Although the existence of
a
cyanobacterial timekeeping mechanism is now established, we are still trying to
understand how this circadian oscillator functions. A satisfactory
understanding
will
require explaining metabolic control of the oscillator, describing the mechanism
of
oscillation, and, to complete the circuit, revealing patterns of metabolic
regulation
by the oscillator. With this goal in mind, folks in my lab ask questions about
the
physiological and biochemical processes that generate and maintain circadian
rhythms. Experimentation in the laboratory exploits contemporary physiological,
genetic and biochemical techniques and, as often as not, provides answers to our
questions. We also take advantage of insights gained from comparative genomics.
Over one hundred prokaryotic genomes,ten from diverse cyanobacteria,have
been completely sequenced. This continuously expanding sequence database is
invaluable to us while assessing the nature of newly discovered genes and the
potential function of novel gene products.
We also maintain an interest in bacterial signal transduction. Bacteria use
two-component regulatory systems to couple environmental dynamics to an
adaptive response. Ordinarily, that response is environmentally relevant gene
expression. The prototypical two-component system includes a membrane spanning,
sensory kinase and a DNA-binding, response regulator protein. Our principle
questions concern sensory kinase function. How is environmental signal
specificity
determined? What is the mechanism of transmembrane signal transduction? And,
because multiple systems function within an organism (Thermosynechococcus
elongatus BP-1 has 16 two-component systems, Escherichia coli K-
12 has 29, Bacillus subtilis 168 has 36, Synechocystis sp.
strain
PCC 6803 has 40, and Anabaena sp. strain PCC 7120 has nearly 60), we
also want to understand how a sensory kinase recognizes the appropriate response
regulator protein.
Curiously, aspects of these two research areas, circadian
clocks
and signal transduction, have recently converged at a single protein. We have
uncovered a sensory kinase that receives environmental cues directly from the
circadian clock. The clock's cues are likely "time of day" information. What is
time
of day information? How is it transferred to the sensory kinase? What metabolic
activities are then regulated by specific time of day information?
Exactly!
Selected publications
Williams, S.B., I. Vakonakis, S.S. Golden, and A. LiWang (2002). Structure and function from the circadian clock
protein KaiA of Synechococcus elongatus: A potential clock input mechanism. Proc Natl Acad Sci USA
99:15357-62.
Iwasaki, H., S.B. Williams, Y. Kitayama, M. Ishiura, S.S. Golden, and T. Kondo (2000). A KaiC- interacting sensory
histidine kinase, SasA, necessary to sustain robust circadian oscillation in cyanobacteria. Cell
101:223-33.
Schmitz, O., M. Katayama, S.B. Williams, T. Kondo, and S.S. Golden (2000). CikA, a bacteriophytochrome that
resets the cyanobacterial circadian clock. Science 289:765-8.
Williams, S.B. and V. Stewart (1999). Functional similarities among two- component sensors and methyl-accepting
chemotaxis proteins suggest a role for linker region amphipathic helices in transmembrane signal transduction. Mol
Microbiol 33::1093-1102.
Williams, S.B. and V. Stewart (1997). Discrimination between structurally related ligands nitrate and nitrite controls
autokinase activity of the NarX transmembrane signal transducer of Escherichia coli K-12. Mol
Microbiol 26::911-25.
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