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Non-Markovian models of intracellular transport in a heterogeneous environment

异质环境中细胞内运输的非马尔可夫模型

基本信息

批准号：
EP/N018060/1
负责人：
Sergei Fedotov
金额：
$ 47.29万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FN018060%2F1
关键词：
Non Markovian models intracellular transport

项目摘要

Transport of all kinds of components within the cell - from vesicles along the cytoskeleton through to transcription factors along DNA - is fundamental to cell function and health. Neurons are particularly susceptible to small changes in vesicle transport, which underlie motor neuron disease and may also contribute to neuronal degeneration seen in Alzheimer's disease and during ageing. Despite experimental facts that intracellular transport is heterogeneous and non-Markovian with subdiffusive and superdiffusive regimes most mathematical models for vesicles trafficking are Markovian and homogeneous. The main challenge for our Manchester interdisciplinary team is to obtain new non-Markovian models of heterogeneous intracellular transport supported by experiments. These models will provide a tool set for analysing transport processes in a much more realistic way, opening the way for greatly improved analysis and ultimately understanding of these highly complex cellular behaviours. This will allow other researchers to formulate and test new hypotheses. In the long term, therefore, non-Markovian models have the potential to lead to insight into neurological diseases, ageing and other processes that involve intracellular transport such as bacterial and viral infection. Such knowledge will be important for developing new treatments. Our project combines three different approaches: mathematical modelling, numerical modelling and experimental validation, which complement each other. This strategy will provide multidisciplinary study of the intracellular transport problem and ensure maximum impact across and within several disciplines. Our project will allow applied mathematicians (PI and RA), cell biologists and biophysicists (Co-Is and Project Partners) to collaborate thus making significant advances in intracellular transport research and support a cross-disciplinary dissemination.

细胞内各种成分的运输--从沿着细胞骨架的囊泡到沿着沿着DNA的转录因子--是细胞功能和健康的基础。神经元特别容易受到囊泡运输的微小变化的影响，这是运动神经元疾病的基础，也可能导致阿尔茨海默病和衰老过程中出现的神经元变性。尽管实验事实，细胞内运输是异质性和非马尔可夫亚扩散和superdiffusive制度的数学模型的囊泡贩运马尔可夫和同质。我们的曼彻斯特跨学科团队的主要挑战是获得实验支持的异质细胞内运输的新的非马尔可夫模型。这些模型将提供一套工具，以更现实的方式分析运输过程，为大大改进分析和最终理解这些高度复杂的细胞行为开辟道路。这将使其他研究人员能够制定和测试新的假设。因此，从长远来看，非马尔可夫模型有可能导致深入了解神经系统疾病，衰老和其他涉及细胞内转运的过程，如细菌和病毒感染。这些知识对于开发新的治疗方法非常重要。我们的项目结合了三种不同的方法：数学建模，数值建模和实验验证，它们相辅相成。这一战略将提供多学科研究的细胞内运输问题，并确保最大限度地影响跨和几个学科内。我们的项目将允许应用数学家（PI和RA），细胞生物学家和生物药理学家（Co-Is和项目合作伙伴）合作，从而在细胞内转运研究方面取得重大进展，并支持跨学科传播。