Administrative Appointments
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Professor, Developmental Biology (1989 - Present)
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Professor, Biochemistry (1959 - Present)
Honors & Awards
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Abbott Lifetime Achievement Award, American Society for Microbiology (1997)
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Wilson Professor of Biochemistry, Stanford Medical School (1995)
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Thomas Hunt Morgan Award, Genetics Society of America (1992)
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Prize for Basic Medical Research, Waterford (1981)
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Lasker Award, Basic Medical Research (1980)
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Elected Member, American Academy of Arts and Sciences (1970)
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Elected Member, National Academy of Sciences USA (1970)
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U.S.Steel Award in Molecular Biology, - (1970)
Professional Education
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B. S., Purdue University, Science (1950)
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Ph. D., California Institute of Technology, Biology and Chemistry (1955)
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Postdoctoral Fellow, Institute Pasteur, Paris, France, Microbial Physiology (1956)
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Assistant Professor, Washington University Medical School, Microbiology (1958)
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Assistant Professor, Stanford Medical School, Biochemistry (1959)
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Professor, Stanford Medical School, Biochemistry (1966)
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Professor, Stanford Medical School, Developmental Biology (1989)
Current Research and Scholarly Interests
How are genes regulated to construct a developmental program? How do signals received from other cells change the program and coordinate it for organized multicellular development? The approach taken by our laboratory group to answer these questions utilizes biochemisty and genetics; genetics to isolate mutants that have particular defects in development and biochemistry to determine the molecular basis of the defects.
We study swarming and fruiting body development in Myxococcus. They are constantly moving as they grow maximizing their access to oxygen. When starving but still able to synthesize protein, these bacteria stop growing and initiate a developmental program. After a detailed assessment of their nutritional state and the number of cells, they aggregate to form fruiting bodies which contain about 100,000 spore cells and which have a species-specific shape. Fruiting bodies form through a regular sequence of morphological changes, finishing with the differentiation of rod-shaped growing cells into spherical, thick-walled spores. Biochemical changes parallel the morphological changes. New proteins are synthesized at particular times during aggregation and sporulation. A series of 30 developmentally regulated promoters have been found, each of which becomes active at a characteristic time. Mutants that have lost the ability to produce particular extracellular signals necessary for swarming or for fruiting body development have been isolated. These mutants are used to dissect the genetic program and to isolate and identify the signals.
The mutants have uncovered four different signals. One signal synchronizes theTwo signals which function in the same regulatory pathway have been chemically identified. The earlier of the two is water soluble and diffusible; it can signal when cells are distant from each other. The later signal is a 17 kDa protein that is cell bound and requires a detergent to extract it from cells. This molecule signals when cells are close together, and its transmission depends on the proper alignment of cells. The later signal is a morphogen. It induces the cells to aggregate into ridge-like heaps that move as travelling waves. Later the aggregates become hemispherical mounds, and eventually species-specific fruiting bodies. The later signal also induces cells within the fruiting body to differentiate myxospores. One signal can do these several different things because each has a different threshold signal intensity.
Graduate and Fellowship Programs
All Publications
- Interconnected cavernous structure of bacterial fruiting bodies PLoS Comp Biol 2013; 8
- Study of elastic collisions of Myxococcus xanthus in swarms Phys Biol 2011; 8
- M. xanthus swarms are driven by growth and regulated by a pacemaker J Bacteriol 2011; 193: 5898-5904
- A cascade of coregulating enhancer binding proteins initiates and propagates a multicellular developmental program. Proceedings of the National Academy of Sciences USA 2011; 108: E431-E439
- Periodic Reversal of Direction Allows Myxobacteria to Swarm Proc Natl Acad Sci USA 2009; 106: 1222-1227
- Are there lateral as well as polar engines for A motile gliding in myxobacteria? J Bacteriol 2009; 191: 5336-5341
- Are there lateral as well as polar engines for A motile gliding in myxobacteria? J Bacteriol 2009; 191: 5336-5341
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Spatial control of cell differentiation in Myxococcus xanthus
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2000; 97 (16): 9098-9103
Abstract
Myxococcus xanthus develops species-specific multicellular fruiting bodies. Starting from a uniform mat of cells, some cells enter into nascent fruiting body aggregates, whereas other cells remain outside. The cells within the fruiting body differentiate from rods into spherical, heat-resistant spores, whereas the cells outside the aggregates, called peripheral cells, remain rod-shaped. Early developmentally regulated genes are expressed in peripheral cells as well as by cells in the fruiting bodies. By contrast, late developmental genes are only expressed by cells within the nascent fruiting bodies. The data show that peripheral cells begin to develop, but are unable to express genes that are switched on later than about 6 h after the start of development. All of the genes whose expression is limited to the fruiting body are dependent on C-signaling either directly or indirectly, whereas the genes that are equally expressed in peripheral rods and in fruiting body cells are not. One of the C-signal-dependent and spatially patterned operons is called dev, and the dev operon has been implicated in the process of sporulation. It is proposed that expression of certain genes, including those of the dev operon, is limited to the nascent fruiting body because fruiting body cells engage in a high level of C-signaling. Peripheral cells do less C-signaling than fruiting body cells, because they have a different spatial arrangement and are at lower density. As a consequence, peripheral cells fail to express the late genes necessary for spore differentiation.
View details for Web of Science ID 000088608000062
View details for PubMedID 10922065
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Myxococcus cells respond to elastic forces in their substrate
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1999; 96 (14): 8052-8057
Abstract
Elasticotaxis describes the ability of Myxococcus xanthus cells to sense and to respond to elastic forces within an agar gel on which they rest. Within 5 min of the application of stress, each cell begins to reorient its long axis perpendicular to the stress force. The cells then glide in that direction, and the swarm becomes asymmetric. A quantifiable assay for the strength of elasticotaxis is based on the change in swarm shape from circular to elliptic. By using a collection of isogenic motility mutants, it has been found that the ability to respond to stress in agar depends totally on adventurous (A) motility, but not at all on social (S) motility or on the frz genes. In fact, S- mutants (which are moving only by means of A motility) respond to the applied stress more strongly than does the wild type, despite the fact that their spreading rates are slower than that of the wt strain. Based on the swarming and elasticotactic phenotypes of isogenic frizzy strains that were also defective either in A or S motility, frz behaves as if part of the S motility system.
View details for Web of Science ID 000081342100083
View details for PubMedID 10393946