Dynamics of cellular proliferation and maturation; dynamics of gene regulation

细胞增殖和成熟的动态；

• 批准号: 36920-2013
• 负责人: Mackey, Michael
• 金额: $ 5.03万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630090
• 关键词: Dynamics; cellular; proliferation; maturation; dynamics

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.

本研究将原核生物和真核生物的基因调控与整个器官水平上造血细胞增殖和成熟的调控结合起来进行探索，其长期目标是增加一个系统的目录，在其中我们可以了解它们的动态调控，以及在单细胞水平上了解噪声在决定群体水平反应中的作用。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态，并为我们对这些位于所有生物过程核心的系统的知识目录增加了知识。本基金申请期的目标是同时探索半乳糖调节的遗传和代谢方面（这是以前在数学建模环境中没有做过的事情），以及理解海胆胚胎中基因调控的时间和空间方面在生成模式形成中的相互作用。我的造血工作的长期目标是开发一个完整的数学模型，正常器官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血细胞群体的观察，以极大的优势，解开各种细胞调节机制负责稳态。在此期间，我更直接的目标是建立一个精确的巨核细胞核复制和血小板形成的调控模型。这一过程在生理学上是有趣的（因为它涉及到没有有丝分裂的核复制），并且由于血小板生成素介导的状态依赖性延迟而涉及到重要的新数学。