NSF-BSF: Mechanism of Cuticle Remodeling by Hypoxia

皮肤是动物内部和外部世界之间的防线，皮肤的结构和功能影响生物体的生存。这项研究调查了皮肤结构和功能如何在低氧条件下（缺氧）发生变化，并将阐明相关的生物学机制。可塑性反应和低氧适应对于理解呼吸和器官稳定性和功能非常重要。此外，由于许多动物生活在氧气水平波动的栖息地（例如，这项研究将有助于了解动物如何在具有挑战性的生态位中生存。这项研究将测试的假设，环境缺氧影响皮肤渗透性，并将确定特定的分子和调控过程中涉及的线虫秀丽隐杆线虫。像所有的动物一样，C。秀丽隐杆线虫全身都是皮肤，最外层的皮肤叫做角质层。角质层富含胶原蛋白，这是动物王国中常见的蛋白质，但由于种类繁多，很难研究。该项目将扩大对胶原蛋白和其他调节胶原蛋白结构和功能的蛋白质的理解，以及对皮肤结构和功能的影响。研究人员将通过开发和传播播客和教育视频来扩大他们的社区外联活动，这些播客和教育视频传达科学研究成果，并突出来自不同背景的个人对科学研究的贡献;通信将以四种不同的语言提供。这项由NSF-BSF项目支持的合作将为美国和以色列的学生和博士后研究员之间的研究交流提供一个富有成效的平台。皮肤是一种多功能器官，是动物内部和外部环境之间的屏障和沟通界面。皮肤的中心组成部分是生物分子的三维网络，细胞外基质，其由蛋白质组成，包括许多形式的胶原蛋白。目的是了解缺氧如何影响皮肤的结构和功能，并利用C。优雅的模特将检验两个假设：（1）角质层结构响应于缺氧而重塑和修饰;（2）缺氧诱导因子1（HIF-1）通过翻译后修饰以脯氨酸羟基化依赖性方式调节角质层结构。该项目将使用遗传，细胞和生理分析评估缺氧对角质层重塑的影响;使用靶向蛋白质组学分析比较暴露于缺氧或常氧的动物角质层的蛋白质组成;并确定HIF-1在缺氧中控制角质层重塑的机制使用生物化学，成像和遗传方法。这项研究可能会对理解皮肤在调节和适应波动的环境氧气水平方面所起的作用产生变革性的影响。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The skin is a line of defense between an animal’s interior and the external world, and the structure and function of the skin affects organismal survival. This research investigates how skin structure and function change in response to low oxygen conditions (hypoxia) and will elucidate the underlying biological mechanisms involved. Plastic responses and adaptation to low oxygen are important for understanding respiration and organ stability and function. Moreover, since many animals live in habitats where oxygen levels fluctuate (e.g., in water or underground burrows), this research will help understand how animals survive in challenging ecological niches. This study will test the hypothesis that environmental hypoxia impacts skin permeability and will identify specific molecules and regulatory processes involved, in the nematode Caenorhabditis elegans. Like all animals, C. elegans is covered with skin, and the outermost skin layer is called the cuticle. The cuticle layer is rich with collagen proteins, which are common proteins in the animal kingdom but can be difficult to study because of the many varieties. This project will expand the understanding of collagen and other proteins that regulate collagen structure and function, and the effects on skin structure and function. The researchers will expand their community outreach activities by developing and disseminating podcasts and educational videos that communicate scientific research results and highlight the contributions of individuals from different backgrounds to scientific studies; communications will be made available in four different languages. This collaboration supported by the NSF-BSF program will provide a fruitful platform for research exchanges between students and postdoctoral fellows in the United States and Israel.Skin is a multifunctional organ that serves as a barrier and a communication interface between an animal’s interior and the external environment. A central component of the skin is a three-dimensional network of biological molecules, the extracellular matrix, which is composed of proteins, including many forms of collagen. The objective is to understand how hypoxia affects the structure and function of the skin and decipher the cellular and molecular mechanisms underlying these processes, using C. elegans as a model. Two hypotheses will be tested: (1) the cuticle structure is remodeled and modified in response to hypoxia; (2) Hypoxia Inducible Factor 1 (HIF-1) regulates cuticle structure in a proline-hydroxylation-dependent manner, via post-translational modification. The project will assess the impact hypoxia has on cuticle remodeling using genetic, cellular, and physiological analyses; compare the protein composition of the cuticle in animals exposed to hypoxia or normoxia using targeted proteomics analysis; and determine the mechanism by which HIF-1 controls cuticle remodeling in hypoxia using biochemical, imaging, and genetic approaches. The proposed research could have a transformative impact on the understanding of the role skin plays in adjusting and adapting to fluctuating environmental oxygen levels.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.