Mathematical Modelling and Computational Simulation Studies of Flagellate Motility

细胞游泳几乎完全是通过纤毛和鞭毛这两种细长的附属物中的一种来驱动的，尽管我们关注的是后者。虽然鞭毛的超微结构在原核生物和真核生物之间不同，但统一的和基本的微观力学原理适用于鞭毛细胞生物学的不同领域，因此受相同的基本机制支配。这种机制的重要性以表面游动为例--这对于了解细菌在表面定植中的行为至关重要，从而对生物膜的启动以及精子细胞与微型设备和女性生殖道表面的相互作用至关重要。进一步的例子包括鞭毛的控制和调节，以及为什么它采用任何给定的拍子模式，对于这种模式，有许多学派的思想，但最少的机械分析，尽管后者对完善我们的理解是有用的。这个理论项目的战略目标将是通过数学建模和计算模拟来进一步发展我们对鞭毛虫运动的力学理解。具体地说，该项目旨在开发新的软件来对鞭毛虫进行高精度的数值模拟，然后将其用于研究复杂的游泳行为和力学。此外，还将对不同微生物中鞭毛的调控进行理论研究，审查该领域最近的假设，并旨在通过考虑其他结构特征来扩展目前的理解。一个例子是研究原生寄生虫利什曼原虫属运动的机械基础，这种原生寄生虫每年感染多达100万人。第一项研究的目标将是描述和了解利什曼原虫运动性的一些方面，如细胞被鞭毛拖曳而不是被推动，以及细胞体与其他鞭毛相比非常大的事实，如何影响它们在生活史的游泳阶段的行为。这包括表面游动行为，伴随着上皮附着和脱离，而寄生虫驻留在其宿主沙蝇体内。它还包括这些细胞在背景流中的行为，这与人类感染初期寄生虫的血流形式有关，利什曼原虫的这两个方面的行为都没有受到详细的机械分析和计算模拟的影响。还将探讨与牛津大学邓恩病理学院的Eva Gluenz和Richard Wheeler博士合作进行更多研究的前景，以进一步提高我们对利什曼原虫运动性的理解。该项目的进一步目标可以包括对生物学文献和生物学同事提出的鞭毛调节假想机制进行机械分析。一个例子是，真核细胞鞭毛内空间不均匀的分子马达刚性是否解释了鞭毛在一种被称为超激活的过程中的不对称，这一过程被观察到是哺乳动物自然受精所必需的。这些后一种研究还需要进一步发展细丝弹性流体动力学模拟，因此，除了生物学和模型的新颖性之外，从计算物理的角度来看，这种研究也将是新颖的。因此，该项目属于EPSRC的(I)数学生物学(Ii)流体动力学和(Iii)连续介质力学的研究领域。

Cellular swimming is almost exclusively actuated via one of two types of slender appendages, cilia and flagella, though our focus is the latter. While flagella ultrastructure differs between prokaryotes and eukaryotes, unifying and fundamental micromechanical principles apply and thus the diverse areas of flagellate cellular biology are governed by the same underlying mechanics. The importance of such mechanics is exemplified by surface swimming - vital in understanding bacterial behaviour in surface colonisation and thus biofilm initation as well as sperm cell interactions with the surfaces of microdevices and the female reproductive tract. Further examples include the control and regulation of the flagellum and why it adopts any given beat pattern, for which there are numerous schools of thought but minimal mechanical analyses, despite the usefulness of the latter in refining our understanding. The strategic aim of this theoretical project will be to further develop our mechanical understanding of flagellate motility by mathematical modelling and computational simulation. Specifically, this project aims to develop new software to perform high-accuracy numerical simulation of flagellates, which will then be used to examine complex swimming behaviours and mechanics. This will be complemented by a theoretical study of the regulation and control of flagella in different microorganisms, examining recent hypotheses in the field and aiming to extend current understanding via consideration of additional structural features. One example will be the study of the mechanical fundamentals for the motility of the genus of protist parasites, Leishmania, which infects up to 1 million humans each year. The objective of a first study will be to characterise and understand how aspects of Leishmania motility, such as the fact the cells are dragged along by their flagella rather than pushed and the fact the cell bodies are very large compared to other flagellates, impacts on their behaviour during the swimming stages of their life cycle. This includes surface swimming behaviour, with epithelial attachment and detachment, while the parasite is resident in its host, the sandfly. It also includes the behaviour of these cells in background flows, as is relevant for bloodstream forms of the parasite in the initial stages of human infection, and neither aspect of Leishmania's behaviour has been subject to detailed mechanical analysis and computational simulation. The prospect of additional studies in collaboration with Drs Eva Gluenz and Richard Wheeler, Dunn School of Pathology, University of Oxford to further improve our understanding of Leishmania motility will also be explored. Further objectives for the project can include the mechanical analysis of hypothesised mechanisms for flagellar regulation within the biological literature and from biological colleagues. One example is whether spatially heterogeneous molecular motor rigor within the eukaryotic flagellum explains the asymmetry of the flagellum during a process known as hyperactivation, which has been observed to be necessary for natural fertilisation in mammals. These latter studies will also require the further development of filament elastohydrodynamic simulations and thus, in addition to biological and modelling novelty, such studies will also be novel from a computational physics viewpoint. Consequently, this project falls within the EPSRC research areas of (i) mathematical biology (ii) fluid dynamics and (iii) continuum mechanics.