COMPUTER ANALYSIS OF AGING IN DICTYOSTELIUM

本申请书中提出的研究将继续努力 定义代谢转变期间的限速事件 模式系统中的分化、衰老和死亡--网柄网柄菌 盘状骨。正在测试的假设是，对 导致分化和衰老的生化机制必须是 寻求在复杂和集成的水平上使用系统分析 比目前所考虑的任何理论所涵盖的要大得多。这个 对这一假设的最终检验是对 所构建的动力学模型。 我们正在获取建造、测试和测试所需的数据 在新陈代谢的各个领域继续扩展模型 发育和衰老。具体来说，我们将获得必要的数据(1) 模拟两种细胞在正常情况下的碳水化合物代谢 稳态状态下的血糖微扰与分化 条件，(2)构造稳态(TFLUX)和转换 (METASIM)戊糖代谢模型，(3)构建过渡模型 以及(4)构建柠檬酸循环的过渡模型 三种代谢性细胞中的碳水化合物代谢 类型。

The research proposed in this application will continue our efforts to define rate-limiting events during the metabolic transitions essential to differentiation, aging and death in the model system, Dictyostelium discoideum. The hypothesis being tested is that an understanding of the biochemical mechanisms responsible for differentiation and aging must be sought using a SYSTEMS analysis, at a level of complexity and integration much greater than that encompassed by any theory thus far considered. The ultimate test of this hypothesis is the demonstrated predictive value of kinetic models which are constructed. We are acquiring the data necessary for the construction, testing and continued expansion of models in various areas of metabolism essential to development and aging. Specifically, we will obtain the data necessary (1) to simulate carbohydrate metabolism in the two cell types during normal differentiation and during glucose perturbation under steady-state conditions, (2) to construct a steady-state (TFLUX) and transition (METASIM) model of pentose metabolism, (3) to construct a transition model of the citric acid cycle, and (4) to construct transition models of carbohydrate metabolism in the three metabolically distinguishable cell types.