Towards a theory linking hematopoietic stem cells, foraging ecology, antipredator behavior, and immune defense

建立一种将造血干细胞、觅食生态学、反捕食行为和免疫防御联系起来的理论

• 批准号: 0924195
• 负责人: Marc Mangel
• 金额: $ 29.74万
• 依托单位: University of California-Santa Cruz
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0924195&HistoricalAwards=false
• 关键词: Towards; theory; linking; hematopoietic; stem

The stem cells found in the bone marrow produce a variety of cells that are required for the organism to function, such as red blood cells and immune cells. In general, bone marrow stem cells are rarely active, but when they are active it is in response to the needs of the organism, which sends signals to the bone marrow. Thus, an organism foraging for food or fleeing a predator will send a different signal (for red blood cells) to the bone marrow than an organism that is fighting off a bacterial or viral infection (immune cells). The proposed work will be the first to develop a quantitative framework for modeling the link between the needs of the entire organism and the bone marrow stem cells. To do so requires models at two different levels of biological structure: one for the foraging/anti-predator responses and one for the bone marrow stem cells. A third model is needed to link the two levels. The models developed for this work will lead to testable predictions ranging from animal behavior to the aging process that can be verified by colleagues in experimental and field settings. In addition to introducing a fundamentally new approach into stem cell biology, the work has a wide range of potential applications in developmental biology, epigenetics, life history theory, homeostasis, aging, animal behavior, and medicine. Educational components of the work include training graduate students and the development of K-12 modules that will help students see the unity of biology and the utility of mathematical methods for understanding biological problems.

骨髓中发现的干细胞产生生物体功能所需的各种细胞，如红细胞和免疫细胞。一般来说，骨髓干细胞很少活跃，但当它们活跃时，它会响应生物体的需要，向骨髓发送信号。因此，觅食或逃离捕食者的生物体将向骨髓发送与抵抗细菌或病毒感染（免疫细胞）的生物体不同的信号（红细胞）。这项工作将首次建立一个定量框架，用于模拟整个生物体和骨髓干细胞需求之间的联系。要做到这一点，需要两个不同层次的生物结构模型：一个是觅食/抗捕食反应模型，另一个是骨髓干细胞模型。需要第三种模式将这两个层面联系起来。为这项工作开发的模型将导致从动物行为到衰老过程的可测试预测，这些预测可以由同事在实验和现场环境中验证。除了将一种全新的方法引入干细胞生物学之外，这项工作在发育生物学、表观遗传学、生活史理论、体内平衡、衰老、动物行为和医学方面具有广泛的潜在应用。这项工作的教育部分包括培训研究生和开发K-12模块，这将帮助学生看到生物学的统一性和数学方法在理解生物学问题中的实用性。