The goal of our proposed research is to understand the molecular mechanisms underlying thermotaxis in the fruitfly, Drosophila melanogaster. Thermotaxis, which is the movement towards a preferred temperature, has been studied in a wide range of vertebrate and invertebrate organisms. However, only a few of the genes and proteins required for temperature discrimination are known. There are two rationales for the proposed research. First, thermotaxis in insects has potential medical relevance, as the host-seeking behaviors of disease spreading vectors, such as the malaria-spreading insect, Anopheles gambiae, appear to involve temperature sensation. Thus, identification of the proteins essential for this behavior may lead to approaches to interfere with it. Drosophila homologs of TRP channels, which are thermosensors in mammals, also function in thermotaxis. Since several thermoTRPs in mammals are also regulated by aversive chemicals, we propose that Drosophila thermoTRPs may be targets for insect repellents. The discovery of the molecular targets for repellents has medical implications, given that mosquito-borne disease is a worldwide health problem. Second, the observations that TRPs are themosensors in flies and mammals raise the possibility that other proteins that function in thermosensation may be shared. Thus, identification of genes and proteins that function in Drosophila thermotaxis may provide new insights into mammalian thermosensation. To characterize thermotaxis and thermoTRPs, we propose to use a multidisciplinary approach, using a combination of genetics, biochemistry, cell biology, molecular biology and electrophysiology.
The specific aims of the current proposal are to: 1) test the hypothesis that a TRP channel (Painless) functions in thermotaxis in adult flies, 2) test the hypothesis that thermoTRPs are targets for insect repellents, 3) test the hypothesis that the TRPV channels (Nanchung and Inactive) operate in combination for larval thermotaxis, and 4) test the hypothesis that rhodopsins function in a thermotaxis signaling pathway. This last aim is concerned with testing the proposal that rhodopsins are direct thermosensors, which may account for the long-known phenomenon that dark-noise and spontaneous activation of rhodopsin is temperature sensitive. A long-term goal of the proposed research is to apply the insights on Drosophila thermoTRPs to identify improved insect repellents and to test the efficacies of drugs that inhibit thermally-driven thermotaxis behaviors that could be applied to medically important Diptera.

Public Health Relevance

The proposed research is concerned with identifying the genes and proteins that are important for thermotaxis and the responses to insect repellents, in the fruitfly. A long-term goal of the proposed research is to apply the insights on fruitfly to identify improved insect repellents and to test the efficacies of drugs that inhibit thermally-driven thermotaxis behaviors that could be applied to medically important insects, such as those that spread malaria and West Nile Virus.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
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Tompkins, Laurie
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Johns Hopkins University
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Venkatachalam, Kartik; Luo, Junjie; Montell, Craig (2014) Evolutionarily conserved, multitasking TRP channels: lessons from worms and flies. Handb Exp Pharmacol 223:937-62
Liu, Sha; Lamaze, Angelique; Liu, Qili et al. (2014) WIDE AWAKE mediates the circadian timing of sleep onset. Neuron 82:151-66
Liman, Emily R; Zhang, Yali V; Montell, Craig (2014) Peripheral coding of taste. Neuron 81:984-1000
Li, Zhengzheng; Ni, Jinfei D; Huang, Jia et al. (2014) Requirement for Drosophila SNMP1 for rapid activation and termination of pheromone-induced activity. PLoS Genet 10:e1004600
Stefan, Christopher P; Zhang, Nannan; Sokabe, Takaaki et al. (2013) Activation of an essential calcium signaling pathway in Saccharomyces cerevisiae by Kch1 and Kch2, putative low-affinity potassium transporters. Eukaryot Cell 12:204-14
Lee, Youngseok; Montell, Craig (2013) Drosophila TRPA1 functions in temperature control of circadian rhythm in pacemaker neurons. J Neurosci 33:6716-25
Fowler, Melissa A; Montell, Craig (2013) Drosophila TRP channels and animal behavior. Life Sci 92:394-403
Shen, Wei L; Kwon, Young; Adegbola, Abidemi A et al. (2011) Function of rhodopsin in temperature discrimination in Drosophila. Science 331:1333-6
Hofmann, Thomas; Chubanov, Vladimir; Chen, Xiaodi et al. (2010) Drosophila TRPM channel is essential for the control of extracellular magnesium levels. PLoS One 5:e10519
Kwon, Young; Kim, Sang Hoon; Ronderos, David S et al. (2010) Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal. Curr Biol 20:1672-8

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