The Drosophila foraging gene: gene regulation, pleiotropy and plasticity

果蝇觅食基因：基因调控、多效性和可塑性

• 批准号: RGPIN-2022-04346
• 负责人: Sokolowski, MarlaB
• 金额: $ 5.83万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=751457
• 关键词: Drosophila; foraging; gene; regulation; pleiotropy

Geneticists traditionally study a single well-defined function associated with a gene. However, many genes have multiple functions (pleiotropy) in different tissues and sometimes even within the same tissue. This proposal investigates how different parts of a gene support different functions, from a gene regulation perspective. We hypothesize that the foraging gene's modular structure and complexity facilitates its multiple functions. We use the fruit fly Drosophila melanogaster with its unsurpassed genetic tool kit. Our efforts are focused on the Drosophila foraging gene that encodes a signalling molecule called cGMP dependent protein kinase. The foraging gene encodes two natural allelic variants called rover and sitter. While foraging, rover flies move more and find more food than sitters. The foraging gene has many functions; in addition to foraging behaviour it modulates learning and memory, sleep, stress responses and social behaviours. In the present grant, we address how, from a molecular perspective, foraging accomplishes its pleiotropic functions in Drosophila social behaviours.  Social behaviours to be studied are: 1) Larval social foraging: Larval social foraging occurs under high-density conditions when 3rd instar larvae form groups who synchronize their downward digging into the liquified food. Under low-density rearing both sitters and rovers forage alone (solitary foraging) whereas under high density, sitters forage in groups (social foraging) while rovers (and larvae with the foraging gene genetically deleted) forage alone. 2) Adult social interaction duration: In groups, adult sitter flies have significantly longer interaction durations than rovers. Social isolation reduces the interaction duration of sitters but not rovers. Genetic analyses tie a number of adult social phenotypes to the foraging gene. The foraging gene is a complex gene comprising about 35kb of DNA. The foraging gene produces many gene products including 21 transcripts an approximately 9 protien isoforms.  The foraging gene is conserved across species and found in multiple systems, tissues and cells throughout development and adulthood of the fly. In the current proposal our objectives are to investigate 1) how the foraging gene's complex structure (multiple promoters, RNA transcripts and protein isoforms) play a modular role in Drosophila social behaviours and, 2) how social behaviours are regulated by interactions between the foraging gene and its epigenetic regulators (G9a, a histone methyl transferase gene, and the microRNA, miR-932), and how the social environment (e.g. social isolation) acts to change these patterns of regulation. This research will build a comprehensive and foundational understanding of how a complex gene affects multiple interacting phenotypes to generate normal individual differences in social behaviour.

遗传学家使用基因的单一定义的功能，有时甚至在同一组织中。促进性是多种功能。除了觅食行为，它在当前的授权中调节了学习和记忆，压力反应和社会行为。 1）幼体社会觅食：幼体社会觅食在高密度条件下发生，他们将其向下挖掘到液化的食物和流浪者的觅食饲料（社会觅食），而流浪者（安德斯觅食），而流浪者（又是流浪者）幼虫觅食的遗传学2）成人的社会互动：在社会隔离中，孤立的孤立持续时间，而不是觅食的基因。大约9种蛋白质的觅食基因是在多个系统中保守的，在整个苍蝇中的组织和细胞都在研究中。 ）在果蝇社会行为中起模块化的作用，2）觅食基因ATS表观遗传调节剂（一种组蛋白甲基转移酶基因D MicroRNA，miR-932）与社会环境（例如社会隔离）的作用之间的社会行为如何作用改变这些调节的模式这项研究将会和基因的基因将多种相互作用的表型影响到社会行为中的个体差异。