NSF-BSF: Mechanism of Cuticle Remodeling by Hypoxia

NSF-BSF：缺氧角质层重塑机制

• 批准号: 2308879
• 负责人: Pamela Padilla
• 金额: $ 99.98万
• 依托单位: University of North Texas
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2308879&HistoricalAwards=false
• 关键词: NSF; BSF; Mechanism; Cuticle; Remodeling

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.

皮肤是动物内部和外部世界之间的一道防线，皮肤的结构和功能影响生物生存。这项研究调查了皮肤结构和功能如何响应低氧条件（缺氧）而变化，并将阐明皮肤结构和功能如何变化。此外，由于许多动物生活在氧气水平波动的栖息地（例如在水中或地下洞穴中），因此塑料对低氧的反应和适应非常重要。这项研究将有助于了解动物如何在具有挑战性的生态环境中生存，该研究将检验环境缺氧影响皮肤渗透性的假设，并将确定线虫中涉及的特定分子和调节过程，就像所有动物一样，秀丽隐杆线虫也被覆盖。皮肤，最外层的皮肤称为角质层，角质层富含胶原蛋白，这是动物界中常见的蛋白质，但由于品种繁多，研究起来很困难。了解胶原蛋白和调节胶原蛋白结构和功能的其他蛋白质，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展活动，以传达科学研究成果并强调个人的贡献。不同的科学研究背景；将以四种不同的语言进行交流。 NSF-BSF 计划支持的这项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果的平台。作为一个障碍和皮肤的核心组成部分是生物分子的三维网络，即细胞外基质，它由蛋白质组成，包括多种形式的胶原蛋白。缺氧会影响皮肤的结构和功能，并以秀丽隐杆线虫为模型来解释这些过程背后的细胞和分子机制，将测试两个假设：（1）角质层结构因缺氧而被重塑和改变； ）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、细胞和生理分析比较蛋白质来评估缺氧对角质层重塑的影响。使用靶向蛋白质组学分析研究暴露于缺氧或常氧的动物的角质层组成，并使用生化、成像和遗传确定 HIF-1 在缺氧条件下控制角质层重塑的机制；拟议的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发挥的作用产生变革性影响。该奖项符合 NSF 的法定使命，并通过使用基金会的智力优势和更广泛的评估而被认为值得支持。影响审查标准。