Multiscale modelling of the microstructural evolution of nervous tissues through high-performance computing

通过高性能计算对神经组织微观结构演化进行多尺度建模

• 批准号: EP/Y001583/1
• 负责人: Ariel Ramirez Torres
• 金额: $ 9.89万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY001583%2F1
• 关键词: Multiscale; modelling; microstructural; evolution; nervous

This project seeks to address a key UK societal challenge in healthcare concerning neurological disorders. It is estimated that neurological conditions are a leading cause of disability in the UK and cause around one-fifth of all deaths yearly. Growing evidence points to the pivotal role of mechanics in neurological disorders and experiments show that neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, and demyelination, lead to changes in nervous tissue microstructure. For instance, autism has been linked to structural plasticity-associated changes leading to alterations in dendritic spines' (tiny protrusions from dendrites, which form functional contacts with neighbouring axons of other neurons) shape and number. From the modelling point of view, efforts have been made to understand the mechanisms underlying such neurological conditions through different theoretical and computational approaches and to elucidate innovative treatment strategies. While advances have been made in the investigation of the function and dysfunction of nervous tissues, many common challenges still need to be addressed and realistic computational simulations based on a multiscale and multiphysics framework tying together the individual pieces of information are still missing. The methodologies developed in this proposal will provide new mathematical infrastructures and generate a fundamental scientific understanding of the nerve tissue by explaining how the relationship among electro-chemo-mechanical interactions at individual scales contributes to its evolution through mathematical modelling and high-performance computing. The outcomes and knowledge generated by the proposal will be of most benefit to the scientific community and, particularly, to healthcare as it aims at understanding some of the mechanisms concerning the progression of neurological disorders and shed light on new information that can be useful for the conception of novel treatment strategies. A long-term goal is to reinforce the scientific community in terms of the technological transfer towards biomedicine through accessible, but sophisticated, computer software.

该项目旨在应对有关神经系统疾病的医疗保健方面的关键社会挑战。据估计，神经系统疾病是英国残疾的主要原因，每年造成所有死亡人数的五分之一。越来越多的证据表明，力学在神经系统疾病中的关键作用，实验表明，神经退行性疾病（例如多发性硬化症，阿尔茨海默氏病和脱髓鞘）会导致神经组织微观结构的变化。例如，自闭症与结构可塑性相关的变化有联系，导致树突状刺的改变（树突的微小突起，它们与其他神经元的相邻轴突形成功能接触）形状和数字。从建模的角度来看，已经努力通过不同的理论和计算方法来了解这种神经系统条件的机制，并阐明创新的治疗策略。尽管在调查神经组织功能和功能障碍时已经取得了进步，但仍需要解决许多共同的挑战，并且基于多尺度和多物理框架将各个信息捆绑在一起的多尺度和多物理框架的现实计算模拟仍缺失。本提案中开发的方法将提供新的数学基础设施，并通过解释各个量表的电化学相互作用之间的关系如何通过数学建模和高表现计算来促进其演变，从而产生对神经组织的基本科学理解。该提案产生的结果和知识将对科学界，尤其是医疗保健最大的好处，因为它旨在理解有关神经系统疾病进展的某些机制，并阐明了新信息，这些信息可用于新的治疗策略的概念。一个长期的目标是通过可访问但复杂的计算机软件来加强科学界的科学界。