Genetic and molecular analysis of multiple functions of the Drosophila melanogaster foraging gene

果蝇觅食基因多种功能的遗传和分子分析

• 批准号: RGPIN-2016-06185
• 负责人: Sokolowski, MarlaB
• 金额: $ 5.46万
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=665558
• 关键词: Genetic; molecular; analysis; multiple; functions

We are interested in understanding how genes interact with the environment to generate individual differences in complex traits. Our research focuses on food-related traits including food search, food intake and triglyceride levels in well-fed and food-deprived environments. We use the fruit fly Drosophila melanogaster model with its unsurpassed genetic tool kit, focussing our efforts on the Drosophila foraging gene. The foraging gene gives rise to two natural variants that we call rover and sitter. Rover flies move more, feed less and have lower triglyceride levels than do sitter flies. It is not known how foraging, which encodes a cGMP dependent protein kinase (PKG) accomplishes its multiple functions to affect individual differences in food-related traits.***We recently discovered that foraging is a complex 35 kb gene with 12 exons, 4 transcription start sites (minimal promoters) and 1 transcription termination site. It produces many gene products including 21 transcripts representing 9 open reading frames. foraging is found in multiple tissue and cell types throughout development and adulthood. ***We hypothesize that the gene's structure and complexity facilitates its many functions. Additionally, we speculate that a given foraging gene product might be used in multiple ways (within the same or different tissues) to affect foraging's multiple functions.***Our specific research questions are:***1) What roles do foraging's minimal promoters, multiple transcripts and protein isoforms play in food-related traits?****2) Which DNA sequences regulate foraging's gene products (guiding them regarding when and where to be expressed in the organism) and how does this expression regulate foraging's food-related traits?***3) What are the underlying molecular mechanisms for the tissue-specific functions of foraging?***4) Which rover and sitter DNA sequence variations segregate with each of the food-related traits?***The molecular dissection of the relationships involving genotype, phenotype and the environment is critical for our understanding of individual differences and how they arise. Because foraging's role in food-related traits is conserved in both invertebrates and vertebrates, we will have the ability to generalise our results to other species. From an applied perspective, this new understanding of the relationship between genotype and phenotype is critical for targeted genetic or chemical manipulations. These techniques are commonly used for insect pest management and conservation. Utilizing these applied endeavours will minimize what are thought to be the "side-effects" of these manipulations and understanding the role of the multiple phenotypes affected by relevant major genes and processes holds the key to unlocking the door.**

我们有兴趣了解基因如何与环境相互作用以在复杂性状中产生个体差异。我们的研究重点是与食品相关的特征，包括食物搜索，食物摄入量和甘油三酸酯水平，并在食物养殖的环境中。我们使用其无与伦比的遗传工具试剂盒使用果蝇果蝇模型，将精力集中在果蝇觅食基因上。觅食基因产生了我们称之为漫游者和保姆的两个自然变体。漫游蝇移动更多，进食较少，甘油三酸酯水平较低。尚不清楚编码CGMP依赖性蛋白激酶（PKG）如何实现其多重功能以影响食物相关性状的个体差异。转录启动位点（最小启动子）和1个转录终止位点。它产生许多基因产品，包括21种代表9个开放式阅读框的成绩单。在整个发育和成年期间，在多种组织和细胞类型中都发现了觅食。 ***我们假设该基因的结构和复杂性有助于其许多功能。此外，我们推测，给定的觅食基因产物可能以多种方式（在相同或不同的组织中）使用以影响觅食的多个功能。 ，多个转录本和蛋白质同工型在与食物相关的性状中发挥作用？**** 2）哪些DNA序列调节觅食的基因产物（指导它们在生物体中何时和何时表达）以及该表达如何调节觅食的食物相关的食物特质？*** 3）组织特异性函数的基本分子机制是什么？*** 4）哪种漫游者和保姆的DNA序列变化与每个与食物相关的性状分离？***分子解剖在涉及基因型，表型和环境的关系中，对于我们对个体差异及其出现的理解至关重要。由于在无脊椎动物和脊椎动物中都保留了觅食在与食物相关的特征中的作用，因此我们将有能力将结果推广到其他物种。从应用的角度来看，对基因型与表型之间关系的新理解对于靶向遗传或化学操作至关重要。 这些技术通常用于害虫管理和保护。 利用这些应用的努力将最大程度地减少被认为是这些操纵的“副作用”，并了解受相关主要基因和过程影响的多种表型的作用，这是解锁门的关键。********************。