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

在骨髓中发现的干细胞会产生机体发挥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，它是对生物体的需求做出反应，生物体向骨髓发送信号。因此，寻找食物或逃离捕食者的有机体向骨髓发送的信号(对于红细胞)将不同于正在抵抗细菌或病毒感染的有机体(免疫细胞)。这项拟议的工作将是第一次开发一个量化框架，对整个生物体的需求和骨髓干细胞之间的联系进行建模。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/反捕食者反应的模型，另一个是骨髓干细胞的模型。需要第三种模式来连接这两个层面。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，这些预测可以在实验和现场环境中得到同事的验证。除了将一种全新的方法引入干细胞生物学之外，这项工作还在发育生物学、表观遗传学、生活史理论、动态平衡、衰老、动物行为和医学等领域有着广泛的潜在应用。这项工作的教育部分包括培训研究生和开发K-12模块，这些模块将帮助学生看到生物学的统一性，以及数学方法在理解生物问题方面的效用。

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.