Roles and regulation of aqua/glyceroporins in a freeze tolerant amphibian

水/甘油孔蛋白在耐冻两栖动物中的作用和调节

• 批准号: 1121457
• 负责人: David Goldstein
• 金额: $ 56.23万
• 依托单位: Wright State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121457&HistoricalAwards=false
• 关键词: Roles; regulation; aqua; glyceroporins; freeze

Preservation of biological tissues by freezing has application in fields ranging from reproductive technology to conservation of endangered species. However, while scientists can successfully cryopreserve small living structures like eggs and embryos, application of those strategies to larger structures remains challenging. The natural world can provide insights into overcoming those challenges. Many "cold-blooded" animals encounter sub-freezing temperatures in their natural environment and, among the vertebrates, a few species have evolved physiological and biochemical strategies to survive freezing. This project will study one of those species, Cope?s gray treefrog. Freezing imposes daunting challenges for an animal, including potential physical damage from ice, fluctuating tissue oxygenation as the blood freezes and thaws, and disruption of molecular and cellular structures as liquid water freezes and body fluid concentrations change. A key to surviving these challenges is regulation of the distribution of water and dissolved solutes. Ice formation must be restricted to fluids outside of cells, and so water must be able to leave cells rapidly when freezing begins. In addition, some solutes, such as glycerol are cryoprotective and help to preserve molecular and physiological integrity during freezing. Gray treefrogs present a natural model for unraveling the mechanisms behind these capabilities. During the cooling autumn months they accumulate glycerol. They also regulate the expression of proteins ("aquaporins") that facilitate movement of water and glycerol across cell membranes. This project will evaluate how these molecular mechanisms are regulated, what is the resulting impact on cellular properties, and how this contributes to freeze tolerance of the whole animal. This integrative approach provides an excellent framework for training students from high school through PhD level in methods and ideas of molecular physiological regulation, and it will yield novel insights into the challenge of keeping tissues frozen alive.

通过冷冻保护生物组织的保存在从生殖技术到濒危物种的保护等领域中应用。 然而，尽管科学家可以成功地冷冻保存鸡蛋和胚胎等小型生活结构，但将这些策略应用于较大的结构仍然具有挑战性。 自然世界可以提供克服这些挑战的见解。 许多“冷血”动物在其自然环境中遇到亚冻结温度，在脊椎动物中，一些物种已经发展了生理和生化策略，以生存在冻结中。 该项目将研究其中一个物种，Cope's Grey Treefog。 冻结对动物构成了艰巨的挑战，包括冰的潜在物理损害，随着血液冻结和融化而波动的组织氧合，随着液态水冻结和人体流体浓度的变化，分子和细胞结构的破坏。 幸存这些挑战的关键是调节水和溶解溶质的分布。 冰的形成必须仅限于细胞外的液体，因此在冻结开始时，水必须能够快速离开细胞。 此外，某些溶质（例如甘油）是冷冻保护性的，有助于在冷冻过程中保留分子和生理完整性。灰色树蛙提出了一种自然模型，用于揭示这些能力背后的机制。在冷却秋季的几个月中，它们积累了甘油。 它们还调节蛋白质（“水通道蛋白”）的表达，从而促进水和甘油在细胞膜上的运动。 该项目将评估如何调节这些分子机制，对细胞特性的影响是什么，以及这如何有助于冻结整个动物的耐受性。 这种综合方法为分子生理调节的方法和思想培训学生通过博士学位培训学生提供了一个绝佳的框架，它将对保持组织冻结的组织的挑战产生新的见解。