In C. elegans, the decision to enter a developmentally arrested, 'non-aging' dauer larval stage is primarily controlled by a secreted dauer pheromone. Small-molecule components of the dauer pheromone include several ascarylose derivatives, which work synergistically with other unidentified components of the pheromone to induce dauer formation. A detailed understanding of these dauer-inducing small molecules and their mechanism of action would enable the development of chemical tools for the study of dauer formation and for the study of related processes such as development, metabolism, and aging. In this proposal, we will fully characterize the dauer pheromone by performing structure-activity studies on the ascarosides, by identifying the chemical structures of unknown pheromone components showing synergistic activity with the ascarosides, by characterizing the mechanism of action of the pheromone components using epistasis analysis, and by transcriptionally profiling C. elegans treated with the pheromone components. By elucidating how small-molecule pheromones influence C. elegans development, our research may ultimately provide insights into how environmental cues influence human development, metabolism and aging. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM077943-01
Application #
7113324
Study Section
Special Emphasis Panel (ZRG1-F04A-D (20))
Program Officer
Marino, Pamela
Project Start
2006-04-01
Project End
2009-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$43,996
Indirect Cost
Name
Harvard University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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Kim, Kyuhyung; Sato, Koji; Shibuya, Mayumi et al. (2009) Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans. Science 326:994-8
Macosko, Evan Z; Pokala, Navin; Feinberg, Evan H et al. (2009) A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans. Nature 458:1171-5