Collaborative Research - Role of Pulsatile Ca^2+ in Controlling Polarized Hyphal Tip Growth

智力上的优点。 所有生物都有复杂的方式来识别和适应环境，以便它们能够生存或避免恶劣的条件，开发新的食物来源，甚至引起疾病。最近在DNA测序、解码和修饰方法方面的一些进展，以及在统一方法中使用的强大显微镜的技术改进，现在使活细胞内靶向遗传变化的微妙异常影响得以监测。这项研究使用真菌作为模型系统，用于确定细胞如何能够感知其微观环境的变化，并招募高度专业化的蛋白质，这些蛋白质在随后的级联事件中与钙离子结合，从而改变细胞行为。遗传方法将用于全面破坏真菌模式生物中所有已知的关键钙相互作用蛋白，并附加特殊标签，允许监测钙变化和/或多种钙相互作用和相关蛋白的运动，以在活细胞内进行跟踪。这种方法将导致全面了解哪些靶向蛋白质允许细胞以快速和定向的方式生长。该项目的科学影响不仅仅是更好地了解导致小麦严重疾病的模式真菌禾谷镰刀菌中钙信号的生物学。它将为研究钙信号的进化创造一个新的工具箱，钙信号是一种高度保守的古老分子语言，几乎所有生物体都使用这种语言将外部环境信号转化为所需的细胞变化。该项目汇集了一批具有互补背景的科学家，包括：生物化学，细胞生物学，细胞学，进化生物学，真菌生物学，信息学，数学和遗传学。 这个项目的广泛和跨学科的范围将提供一个理想的环境，实践团队为基础的综合问题解决与本科生，研究生和博士后的学生。面对生物学问题迅速增长的复杂性，对这种教育的需求继续增加。由该项目支持的博士后将在不久的将来通过既定的指导计划来指导她开发自己的程序。通过为期一周的实践讲习班和全面的公开网站，其他人将有机会获得所有资源，并接受培训，以使用所开发的工具。钙信号的发现和显微镜技术在这里开发将介绍研究生水平的课程和基于网络的工具。本科生（包括少数民族学生）将通过NSF REU和EPSCoR计划以及宾夕法尼亚州立大学和特拉华州大学的其他现有信贷和推广计划参与该项目。这些努力将帮助参与的学生获得广阔的视野和新技术，以推进学术和工业环境。该真菌模型将揭示动物和植物中其他类似生长形式（即神经元、芽殖和分裂酵母、上皮细胞、根毛、花粉管）中钙信号通路的共享组分，并揭示可能与其进化适应和功能多样性相关的独特属性。真菌Ca 2+信号的独特方面可用于控制疾病。

Intellectual merit. All organisms have sophisticated ways for recognizing and adapting to their environment so they can survive or avoid harsh conditions, exploit new food sources or even cause disease. Several recent advances in methods for sequencing, decoding and modifying DNA and technological improvements in powerful microscopes when used in a unified approach now enable subtle abnormal effects of targeted genetic changes to be monitored inside living cells. This research uses fungi as a model system for determining how cells are able to sense changes in their microscopic environment and recruit highly specialized proteins that bind to calcium ions in a subsequent cascade of events that change the cells behavior. Genetic methods will be used to comprehensively disrupt all known key calcium interacting proteins in a fungal model organism and attach special tags that allow monitoring of calcium changes and/or movement of multiple calcium interacting and related proteins to be tracked inside of living cells. This approach will result in a comprehensive understanding of which targeted proteins allow cells to grow in a rapid and directed fashion. The scientific impacts of this project go beyond better understanding the biology of calcium signaling in the model fungus Fusarium graminearum which causes a serious disease in wheat. It will create a novel toolbox for studying the evolution of calcium signaling, a highly conserved ancient molecular language used by in virtually all organisms for converting external environmental signals into needed cellular changes. The project brings together a group of scientists with complementary backgrounds including; biochemistry, cell biology, cytology, evolutionary biology, fungal biology, informatics, math, and genetics.Broader impacts. The broad and interdisciplinary scope of this project will provide an ideal environment for practicing team-based integrative problem solving with undergraduate, graduate, and postdoctoral students. Faced with the rapidly growing complexity of biological questions, the need for such education continues to increase. A postdoc supported by this project will be mentored to develop her own program in the near future through established mentoring programs. Through hands-on week long workshops and comprehensive publicly available websites, others will have access to all resources and trained to implement the developed tools. The calcium signaling discoveries and microscopy techniques developed here will be introduced in graduate level courses and web-based tools. Undergraduate students (including minority students) will be involved in this project through NSF REU and EPSCoR programs as well as other existing credit and outreach programs at both Penn State and University of Delaware. These efforts will help the participating students gain broad perspectives and new technologies to carry forth into academic and industrial settings. This fungus model will reveal shared components of calcium signaling pathways in other similar growth forms (i.e. neurons, budding and fission yeast, epithelial cells, root hairs, pollen tubes) in animals and plants, and also expose unique attributes potentially relating to their evolutionary adaptation and functional diversity. Unique aspects of fungal Ca2+ signaling may be exploited for controlling disease.