Control of male-female differences in stress responses and survival by sex determination gene transformer.

通过性别决定基因转换器控制应激反应和生存中的男女差异。

• 批准号: RGPIN-2016-04249
• 负责人: Rideout, Elizabeth
• 金额: $ 2.62万
• 依托单位: University of British Columbia
• 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=663358
• 关键词: Control; male; female; differences; stress

OVERVIEW. Biological sex determines many aspects of animal development and physiology, including stress survival, body size, and lifespan. In spite of the importance of sex to these traits, sex is often overlooked as an experimental variable. As a result, little is known about how male-female differences in cellular processes, development, physiology and behaviour cause sex differences in survival, body size or lifespan. Sex hormones explain these differences in some animals; yet sex differences also exist in animals without sex hormones, like insects. Our knowledge of how male-female differences cause sex-biased survival or aging in insects is poor. My long-term research goal is to improve our understanding of how sex differences in fundamental biological processes cause sex bias in these complex traits in insects using the fruit fly, Drosophila, as a model. The focus of this proposal is to study the mechanisms underlying sex differences in starvation survival. My lab discovered a single gene, transformer (tra), that creates male-female differences in starvation survival in Drosophila. Tra is known to control female sexual development, behaviour and reproduction; however, our finding defines a totally new role for Tra in survival. We will combine our unique knowledge of Tra's survival effects with existing genetic tools to identify the relevant differences between males and females that influence survival. To do this, we will pursue the following Goals: ****GOAL 1. Identify the tissues and stage of development in which sex acts to enhance female survival. Our discovery of Tra as a switch between male and female survival provides a powerful tool to unambiguously determine how each tissue and stage of development contributes to sex differences in survival. These studies will allow us to dissect how sexual development and maintenance of sexual identity contribute to male-female differences in survival, and identify tissues that participate in the stress response.***GOAL 2. Characterize the genetic and molecular mechanisms underlying sex-biased survival. Tra is an SR protein, and has been shown to regulate alternative splicing. We will determine the molecular mechanism of Tra's effects on survival by identifying its downstream target genes. These studies will provide novel mechanistic insight into an important question in biology – how do males and females survive differently?***SIGNIFICANCE. This research not only addresses a fundamental question in biology, but it has important agricultural and industrial implications due to male-female differences in survival after pesticide exposure. The knowledge we generate will assist in the development of novel pesticides that equally target males and females. Several industries in Canada (eg. agriculture), will benefit from this knowledge to combat infestations of harmful species such as Drosophila suzukii (soft fruit crops).****** **

概述。生物性别决定了动物发育和生理的许多方面，包括生存压力、体型和寿命。尽管性别对这些特征很重要，但性别作为一个实验变量经常被忽视。因此，人们对男女在细胞过程、发育、生理和行为方面的差异是如何导致生存、体型或寿命方面的性别差异知之甚少。性激素解释了一些动物的这些差异；然而，在没有性激素的动物中也存在性别差异，比如昆虫。我们对雌雄差异如何导致昆虫的性别偏见生存或衰老的了解很少。我的长期研究目标是提高我们对基本生物过程中的性别差异如何导致昆虫这些复杂特征中的性别偏见的理解，以果蝇为模型。本研究的重点是研究饥饿生存中性别差异的机制。我的实验室发现了一个单一的基因，变压器（tra），它在果蝇的饥饿生存中产生了雄性和雌性的差异。已知Tra控制女性的性发育、行为和生殖；然而，我们的发现定义了Tra在生存中的全新作用。我们将把我们对Tra的生存影响的独特知识与现有的遗传工具相结合，以确定影响生存的男性和女性之间的相关差异。为此，我们将努力实现以下目标：****目标1。确定性行为能提高女性存活率的组织和发育阶段。我们发现Tra是男性和女性生存之间的一个开关，这一发现提供了一个强有力的工具，可以明确地确定每个组织和发育阶段是如何影响性别生存差异的。这些研究将使我们能够剖析性发育和性身份的维持如何导致男女在生存方面的差异，并确定参与应激反应的组织。* * *的目标2。描述性别偏见生存的遗传和分子机制。Tra是一种SR蛋白，已被证明可调节选择性剪接。我们将通过鉴定其下游靶基因来确定Tra对生存影响的分子机制。这些研究将为生物学中的一个重要问题——男性和女性如何以不同的方式生存——提供新的机制见解。这项研究不仅解决了生物学中的一个基本问题，而且由于男性和女性在农药暴露后的生存差异，它具有重要的农业和工业意义。我们获得的知识将有助于开发同样针对雄性和雌性的新型杀虫剂。加拿大的几个行业(如……农业)，将从这一知识中受益，以对抗有害物种的侵扰，如铃木果蝇（软果作物）。* * * * * * * *