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防御线，皮肤的结构和功能会影响有机生存。这项研究调查了皮肤结构和功能如何响应低氧条件（缺氧），并将阐明涉及的潜在生物学机制。塑性反应和对低氧的适应对于理解呼吸和器官稳定性和功能很重要。此外，由于许多动物生活在氧气水平波动（例如在水或地下洞穴中）的栖息地，因此这项研究将有助于了解动物如何在挑战生态壁ches中生存。这项研究将检验以下假设：环境缺氧会影响皮肤渗透性，并将在线虫秀丽隐杆线虫中识别涉及的特定分子和调节过程。像所有动物一样，秀丽隐杆线虫被皮肤覆盖，最外面的皮肤层称为表皮。角质层层富含胶原蛋白，它们是动物界的常见蛋白质，但由于许多变化，可能很难研究。该项目将扩大对调节胶原蛋白结构和功能的胶原蛋白和其他蛋白质的理解，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其社区外展活动，以传达科学研究结果，并强调个人对科学研究的个人的贡献；通信将以四种不同的语言提供。 NSF-BSF计划支持的这项合作将为美国和以色列的学生与博士后研究员之间的研究交流提供一个富有成果的平台。Skin是一种多功能器官，是动物内部和外部环境之间的障碍和通信界面。皮肤的主要成分是生物分子的三维网络，即细胞外基质，由蛋白质组成，包括多种形式的胶原蛋白。目的是使用秀丽隐杆线虫作为模型来了解缺氧如何影响皮肤的结构和功能，并破译这些过程的细胞和分子机制。将检验两个假设：（1）对缺氧的反应进行重塑和修饰； （2）低氧诱导因子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，细胞和物理分析评估缺氧对切割重塑的影响；使用靶向蛋白质组学分析比较暴露于缺氧或正常氧的动物中切菜的蛋白质组成；并确定HIF-1使用生化，成像和遗传方法控制低氧中的角质层重塑的机制。拟议的研究可能会对对皮肤在调整和适应环境氧气的作用的理解的理解产生变革性的影响。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的影响来通过评估来获得的支持。