Dynamics of cellular proliferation and maturation; dynamics of gene regulation

本研究是在全器官水平上对原核生物和真核生物基因调控和造血细胞增殖成熟调控的综合探索。基因调控研究的长期目标是增加系统目录，使我们能够了解它们的动态调控，并了解单细胞水平上噪声在决定种群水平反应中的作用。基因调控的工作是非常基础的，因为我正在探索内在和外在的噪音如何在基因表达水平上塑造和改变动力学，并且正在增加我们对这些系统的知识目录，这些系统位于所有生物过程的核心。本基金申请期的目标是同时探索半乳糖调控的遗传和代谢方面（在数学建模背景下从未做过的事情），并了解海胆胚胎中产生模式形成的基因调控的时间和空间方面之间的相互作用。我在造血方面工作的长期目标是建立一个完整的数学模型，说明正常器官如何通过细胞增殖和成熟来维持自身。我已经能够使用动态振荡的血细胞群的观察，在解开各种细胞调节机制负责体内平衡的巨大优势。在这个资助期间，我更直接的目标是为巨核细胞的核复制和随后的血小板形成的调节建立一个准确的模型。这个过程在生理学上是有趣的（因为它涉及无丝分裂的核复制），并且涉及重要的新数学，因为涉及由血小板生成素介导的状态依赖性延迟。

This research is a combined exploration of gene regulation in prokaryotes and eukaryotes and the regulation of hematopoietic cellular proliferation and maturation at the whole organ level.The long term goal of the research on gene regulation is to add to the catalog of systems in which we can understand their dynamic regulation as well to understand the role of noise at the single cell level in determining population level responses. The work on gene regulation is extremely fundamental in the sense that I am exploring how both intrinsic and extrinsic noise can shape and alter dynamics at the geneexpression level, and is adding to the catalog of knowledge we have for these systems that lie at the heart of all biological processes. The goal for this grant application period is to simultaneously explore the genetic and metabolic aspects of galactose regulation (something that has not been done before in a mathematical modeling context), and to understand the interplay between temporal and spatial aspects of gene regulation in generating pattern formation in the sea urchin embryo.The long term goal of my work on hematopoiesis is to develop a complete mathematical model for how a normal organ maintains itself through cellular proliferation and maturation. I have been able to use observations of dynamically oscillating blood cell populations to great advantage in untangling a variety of cellular regulatory mechanisms responsible for homeostasis. For the duration of this grant period my more immediate goal is to produce an accurate model for the regulation of megakaryocyte nuclear replication and the subsequent formation of platelets. This process is physiologically interesting (since in involves nuclear replication without mitosis) and involves significant new mathematics because of the state dependent delays involved that are mediated by thrombopoietin.