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.
