|ascr#3(C9)-induced changes in intracellular calcium in an ADL chemosensory neuron expressing the calcium indicator GCaMP in wild-type. From Jang, Kim et al, Neuron 2012. PubMed|
The term pheromone is derived from the Greek words pherein (to carry or transfer) and hormon (to excite or stimulate). Pheromones are small molecules that are used widely in the animal kingdom to communicate health, sex, mating status, developmental stage, alarm signals and more. Pheromones can elicit both long-term changes in development via regulation of the neuroendocrine axis, as well as acute changes in behaviors via effects on neuronal and circuit activity. Although responses to pheromone are innate, these responses are nevertheless modulated by internal and external cues. The overall goal of this project is to decode the syntax of pheromone-mediated communication. We expect that this work will lead to a better understanding of the interactions of animals with their environment, and more generally of neuronal signal transduction and circuit functions that generate behaviors. Moreover, many of the chemicals produced by C. elegans are also produced by parasitic nematode species (implicated as agricultural pests and in human diseases); thus, an understanding of the molecular signaling mechanisms in C. elegans may allow us to devise methods for nematode pest control.
C. elegans produces a remarkably complex mix of small chemicals, collectively called ascarosides. Individual ascarosides elicit a range of responses including promoting entry into an alternate stress-resistant developmental stage called the dauer stage, aggregation of adult animals, as well as avoidance or attraction behaviors. We and others have shown that, as in other animals, adult behavioral responses in C. elegans are dependent on internal state and are sexually dimorphic. We are currently collaborating with chemists (Rebecca Butcher, Frank Schroeder) and engineers (Dirk Albrecht, Dongshin Kim) to examine the molecular and neural substrates of responses to single, as well as blends, of ascarosides.
Members of the Axis of (Chemo)Taxis use genetic, genomic and molecular approaches, as well as in vivo calcium imaging and microfluidics-based behavioral assays to ask the following questions:
- How do different chemicals synergize to result in distinct behavioral responses to single chemicals and chemical blends?
- How does context such as starvation modulate developmental and behavioral responses to pheromone?
- Does prior exposure to pheromone alter responses to other chemical stimuli?
- How are pheromone cues detected, encoded and transduced within the nervous system?
- Sims JR, Ow MC, Nishiguchi MA, Kim K, Sengupta P, Hall SE. (2016) Developmental programming modulates olfactory behavior in C. elegans via endogenous RNAi pathways. elife 10.7554/eLife.11642 [PubMed]
- Neal SJ, Park J, DiTirro D, Yoon J, Shibuya M, Choi W, Schroeder FC, Butcher RA, Kim K, Sengupta P. (2016) A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans. G3: Genes, Genomes, Genetics g3.115.026450 [PubMed]
- Neal SJ, Takeishi A, O'Donnell MP, Park J, Hong M, Butcher RA, Kim K,Sengupta P. (2015) Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling eLife. 2015;4:e10110 [eLife]
- Ryan DA, Miller RM, Lee K, Neal SJ, Fagan KA, Sengupta P, Portman DS. (2014) Sex, age, and hunger regulate behavioral prioritization through dynamic modulation of chemoreceptor expression. Curr Biol. 24(21):2509-17. [PubMed]
- Jang, H, Kim K, Neal SJ, Mocosko E, Kim D, Butcher RA, Zeiger DM, Bargmann CI, Sengupta P. (2012) Neuromodulatory state and sex specify alternative behaviors through antagonistic synaptic pathways in C. elegans. Neuron. 75: 585-92 [PubMed]
- Kim K, Sato K, Shibuya M, Zeiger DM, Butcher RA, Ragains JR, Clardy J, Touhara K, Sengupta P (2009) Two Chemoreceptors Mediate Developmental Effects of Dauer Pheromone in C. elegans. Science. 326: 994-998. [PubMed]
Funding: NSF IOS 1256488