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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=568787
• 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 gene expression 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.

这项研究是对原核生物和真核生物中基因调节的综合探索，以及整个器官水平上造血细胞增殖和成熟的调节。 关于基因调控的研究的长期目标是增加系统目录，在该目录中我们可以理解它们的动态调节，以了解噪声在单细胞水平确定人群水平响应中的作用。关于基因调控的工作在探索固有和外在噪声如何塑造和改变基因的动态的意义上是极为基础的。 表达水平，并增加了我们对所有生物过程核心的知识目录。这个赠款申请期的目的是同时探索半乳糖调节的遗传和代谢方面（在数学建模环境中之前没有做过的事情），并了解基因调节在海乌蛋白胚胎中产生模式形成时的时间和空间方面之间的相互作用。 我在造血作品上工作的长期目标是开发一个完整的数学模型，以通过细胞增殖和成熟方式来维持正常器官。我已经能够使用动态振荡的血细胞群体的观察结果，在解开负责稳态的各种细胞调节机制方面具有很大的优势。在此赠款期间，我更直接的目标是为调节巨核细胞核复制和随后的血小板形成提供准确的模型。这个过程在生理上很有趣（因为在没有有丝分裂的情况下涉及核复制），并且涉及大量的新数学，因为涉及的国家依赖性延迟是由血小板素介导的。