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.

这项研究是对原核生物和真核生物中基因调节的结合探索，以及在整个器官水平上对造血性细胞增殖和成熟的调节。基因调节研究的长期目标是增加系统的催化系统，使我们可以理解他们的动态调节，以了解其在单元格中的作用，并在单元格中响应了噪声的作用。从我正在探索固有和外在噪声如何在Geneexpression级别塑造和改变动态的意义上，关于基因调节的工作极为基础，并且正在增加我们对所有生物过程中心的知识目录。这个赠款申请期限的目标是同时探索半乳糖调节的遗传和代谢方面（在数学模型上没有做过的事情），并了解基因调节的时间和空间方面的相互作用在生成海洋尿路的长期靶向过程中的长期靶向的时间范围内的时间和空间方面，以使我的工作能够完成水平，以使我能够完成一项正常的工作。细胞增殖和成熟。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。