Dissection of aggression in Drosophila

攻击性是动物进化上保守的一种与生俱来的行为，对动物的生存和进化至关重要。虽然很明显，侵略性是由环境和遗传因素的影响，控制侵略性的分子和细胞机制仍然在很大程度上不确定。在这项申请中，我们建议开发一个长期的研究计划，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果蝇品系和野生捕获的品系中。强大的果蝇遗传学和复杂的分子工具的可用性相结合，将使我们能够获得对动物攻击控制的基本生物学的机械见解。 在寻找参与调节果蝇攻击性的新球员时，我们已经确定了几个重要的基因。例如，我们发现了一个我们命名为和平（Pfs）的基因，它是攻击性行为的一种新的重要调节因子，并首次表明进化上保守的Pfs依赖性MoCo生物合成途径积极促进攻击性。此外，我们还确定了CrzR和其他几个基因的突变导致异常的攻击行为。在这项申请中，未来10-15年拟议研究计划的长期目标是进一步了解我们最近遗传研究中确定的基因的功能，从而阐明控制攻击的复杂分子和细胞网络。三个目标包括：1）测试Pfs依赖性MoCo生物合成途径刺激MoCo依赖性辅酶的活性，这反过来促进特定神经元回路的激活以上调攻击性的假设（1-5岁）; 2）确定神经肽受体CrzR下调攻击性的机制（1-5岁）; 3）表征Pfs，Crz和从我们的遗传方法中鉴定的其他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- 1 - 5岁）。 拟议的研究计划将在分子和细胞水平上为控制攻击提供新颖而重要的见解，并在攻击研究领域开辟新的途径。果蝇的见解可以在脊椎动物中进行测试，并将极大地促进对攻击性基本生物学的理解。拟议的研究还将有助于在麦吉尔神经科学研究中心制定一项关于攻击性研究的长期培训计划，并为研究生和本科生提供极好的培训机会，以获得果蝇遗传学，攻击性和动物行为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.