Dissection of aggression in Drosophila

攻击是动物进化中保守的一种先天行为，对动物的生存和进化至关重要。虽然攻击性显然受到环境和遗传因素的影响，但控制攻击性的分子和细胞机制在很大程度上仍然不清楚。在这一应用中，我们建议开发一个长期研究计划，利用果蝇作为模型来研究领土侵略的分子和细胞机制。攻击性存在于实验室的果蝇品系和野生捕获的品系中。强大的果蝇遗传学和先进的分子工具的结合将使我们能够从机械上洞察控制动物攻击性的基本生物学。在寻找参与调节果蝇攻击性的新参与者的过程中，我们发现了几个重要的基因。例如，我们发现了一个名为和平(PFS)的基因，它是攻击行为的新的重要调节因子，并首次表明进化上保守的依赖PFS的MoCo生物合成途径积极促进攻击性。此外，我们还鉴定了CrzR和其他几个基因，它们的突变导致了异常的攻击行为。在这一应用中，拟议的研究计划在未来10-15年的长期目标是进一步了解从我们最近的遗传学研究中识别的基因的功能，从而阐明控制攻击性的复杂分子和细胞网络。三个目标包括：1)检验PFS依赖的MoCo生物合成途径刺激依赖MoCo的钼酶活性的假设，进而促进特定神经元电路的激活，从而上调攻击性(1-5岁)；2)确定神经肽受体CrzR下调攻击性的机制(1-5岁)；以及3)表征PFS、CRZ和其他通过我们的遗传学方法确定的基因之间的复杂相互作用，并阐明它们在控制攻击行为中发挥作用的分子和细胞网络(1-15岁)。此外，拟议的研究计划将为在分子和细胞水平上控制攻击行为提供新颖和重要的见解，并在攻击研究领域开辟新的途径。来自果蝇的洞察力可以在脊椎动物身上进行测试，这将极大地刺激对理解攻击的基本生物学的研究。这项拟议的研究还将有助于麦吉尔神经科学研究中心制定攻击性研究的长期培训计划，并为研究生和本科生提供绝佳的培训机会，以获得果蝇遗传学、攻击性和动物行为的神经基础方面的经验和专业知识。

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.