Dissection of aggression in Drosophila

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Aggression is an innate behavior evolutionarily conserved in animals, and is essential to the survival and evolution of animals. While it is clear that aggression is influenced by both environmental and genetic factors, the molecular and cellular mechanisms underlying the control of aggression remain largely undefined. In this application, we propose to develop a long-term research program that utilizes Drosophila as a model to study molecular and cellular mechanisms of territorial aggression. Aggression exists in the lab Drosophila strains as well as wild-caught strains. The combination of the powerful Drosophila genetics and the availability of sophisticated molecular tools will allow us to gain mechanistic insights into the fundamental biology of aggression control in animals.     In a search for novel players involved in regulating aggression in Drosophila, we have identified several important genes. For instance, we discovered a gene we named peacefulness (Pfs) as a novel and important regulator of aggressive behaviors, and show for the first time that the evolutionarily conserved Pfs-dependent MoCo biosynthesis pathway actively promotes aggressiveness. In addition, we also identified CrzR and several other genes whose mutations caused abnormal aggressive behaviors. In this application, the long-term objective of the proposed research program over next 10-15 years is to further understand the function of the genes identified from our recent genetic studies, and thus elucidate complex molecular and cellular networks underlying the control of aggression. Three Aims include: 1) Testing the hypothesis that the Pfs-dependent MoCo biosynthesis pathway stimulates the activity of MoCo-dependent molybdoenzymes, which in turn promotes the activation of specific neuronal circuits for up-regulating aggressiveness (years 1-5); 2) Determining the mechanisms by which the neuropeptide receptor CrzR down-regulates aggressiveness (years 1-5); and 3) Characterizing the complex interactions between Pfs, Crz and other genes identified from our genetic approaches, and elucidate molecular and cellular networks in which they function in controlling aggressive behaviors (years 1-15).     The proposed research program will provide novel and important insights into the control of aggression at both molecular and cellular levels, and open new avenues in the field of aggression research. Insights from Drosophila can be tested in vertebrates, and will greatly stimulate research on understanding the fundamental biology of aggression. The proposed research will also help develop a long-term training program on aggression research at the McGill Centre for Research in Neuroscience, and provide excellent training opportunities for graduate and undergraduate students to gain experience and expertise in Drosophila genetics, aggression, and neural basis of animal behaviors.