Evolutionary reconfiguration of signaling cascades

所有的生物都严重依赖于能够感知他们的环境并做出适当的反应来生存。因此，所有细胞都有复杂的系统来完成这一任务。这类系统包括感知环境变化的蛋白质，然后将这种变化信号传递给与它们相互作用的其他蛋白质。通过这种蛋白质相互作用的网络，细胞可以协调复杂的反应，这些反应是在不同的环境压力下生存所必需的，例如温度、pH或盐浓度的变化，甚至暴露在毒素、污染物和化学杀虫剂中。鉴于这些信号网络对于适应环境压力的核心重要性，所涉及的蛋白质在整个进化过程中往往高度保守。这项研究计划使用与人类关系最密切的实验上最容易驯化的生物来研究蛋白质相互作用网络的变化对细胞信号、应激生存以及最终适应新环境的影响的机制。我们将使用真菌模型系统来进化蛋白质相互作用网络中的新连接，将利用不同真菌物种的遗传变异来确定相互作用网络是如何通过自然界的进化而重新配置的，并将剖析支持全球范围内适应不同环境的物种内的特定变化。这项研究使用最先进的分子工具来了解细胞的连接以及这如何影响进化过程。这项工作的结果将使分子遗传学家能够理解细胞信号的新方面，也将为进化生物学家提供关于进化如何在分子水平上发生的新见解。除了使多个科学学科受益外，这项研究还将制定战略，阻止对农业生产力至关重要的杀虫剂抗药性的演变，并制定战略，使微生物具有更强的承受压力和修复受污染环境的能力，从而改善加拿大人的生活。

All living creatures critically depend on being able to sense their environment and mount the appropriate responses in order to survive. As a consequence, all cells have intricate systems to do this. Such systems include proteins that sense environmental change and then signal this change to the other proteins that they interact with. Through such networks of protein interactions, the cell can orchestrate complex responses that are required to survive diverse environmental stresses such as changes in temperature, pH, or salt concentration or even exposure to toxins, pollutants, and chemical pesticides. Given the central importance of these signaling networks for adapting to environmental stress, the proteins involved are often highly conserved throughout evolution. This research program uses the most experimentally tractable organisms that are closely related to humans to study the mechanisms by which changes in the network of protein interactions impact on cellular signaling, survival during stress, and, ultimately, adaptation to new environments. We will use fungal model systems to evolve new connections in protein interaction networks, will exploit the genetic variation in diverse fungal species to determine how interaction networks have been reconfigured by evolution in nature, and will dissect the specific changes within a species underpinning adaptation to divergent environments on a global scale. This research uses state-of-the-art molecular tools to understand the wiring of a cell and how this can influence the course of evolution. The outcomes of this work will allow molecular geneticists to understand new aspects of cellular signaling and will also provide new insights for evolutionary biologists as to how evolution happens at the molecular level. Beyond benefiting multiple scientific disciplines, this research will establish strategies to block the evolution of resistance to pesticides crucial for agricultural productivity as well as strategies to evolve microbes with enhanced capacity to tolerate stress and remediate contaminated environments, thereby improving the lives of Canadians.