Biomathematical analysis of cell invasion: migration of neural crest cells to form the enteric nervous system

细胞侵袭的生物数学分析：神经嵴细胞迁移形成肠神经系统

• 批准号: nhmrc : 436971
• 负责人: Dr Donald Newgreen
• 金额: $ 29.97万
• 依托单位: Murdoch Childrens Research Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/biomathematical-analysis-cell-enteric-nervous/77937
• 关键词: Biomathematical; analysis; cell; invasion; migration

Extending scientific studies to a mathematical level is the way to produce deep understanding and control. Mathematics has been applied less to biology, particularly the biology of development, than to other branches of science, no doubt due to the innate complexity and technical difficulties of seeing and measuring what is actually going on. Labelling, imaging and computational tools to visualise biological processes are only now becoming available. To build our bodies during embryonic development, cells must move; this is called cell migration. The same process occurs throughout life in wound repair. Uncontrolled migration is the hallmark of malignant cancers, where it is called invasion. The molecular mechanisms in cells that allow them to move are just beginning to be understood. However, the big questions determining the general rules of migration are more difficult to approach. Here are some examples of such questions. When to migrate? Where to migrate to? Which pathways? How many cells to migrate? How far? How fast? How to stop? Such simple questions are still unanswered. We are pioneering a novel and unique approach combining imaging of real cells migrating in real tissues (digital time-lapse movies) with mathematical modelling to understand the driving forces of cell migration-invasion. This technology is here applied to a particular example of cell migration where precursor nerve cells migrate all the way along the length of the gastro-intestinal tract in early development. This process gives rise to fatal birth defects associated with migration failure. The development of the nervous system in the gut has features in common with all other migrations and invasions, normal and pathological. A much more profound knowledge of the big picture of the developmentally and clinically crucial process of cell migration-invasion will emerge from this marriage of biological experimentation and mathematical modelling.

将科学研究扩展到数学水平是产生深刻理解和控制的方法。与其他科学分支相比，数学在生物学，特别是发育生物学中的应用较少，这无疑是由于观察和测量实际发生的事情的内在复杂性和技术困难。为了在胚胎发育期间构建我们的身体，细胞必须移动;这被称为细胞迁移。同样的过程发生在整个生命的伤口修复。不受控制的迁移是恶性癌症的标志，在那里它被称为侵袭。细胞中允许它们移动的分子机制才刚刚开始被理解。然而，决定移民一般规则的大问题更难解决。以下是此类问题的一些示例。何时迁移？迁移到哪里？哪些途径？要迁移多少细胞？多远？有多快？如何停止？这些简单的问题仍然没有答案。我们正在开创一种新颖独特的方法，将真实的细胞在真实的组织中迁移的成像（数字延时电影）与数学建模相结合，以了解细胞迁移入侵的驱动力。该技术在此应用于细胞迁移的特定实例，其中前体神经细胞在早期发育中沿胃肠道的长度沿着一直迁移。这一过程导致与移徙失败有关的致命出生缺陷。肠道神经系统的发育与所有其他正常和病理的迁移和入侵具有共同的特征。从生物学实验和数学建模的结合中，我们将对细胞迁移-入侵这一在发育和临床上至关重要的过程的全貌有更深刻的了解。