Mathematical Modelling and Computational Simulation Studies of Flagellate Motility

细胞游泳几乎完全是通过两种类型的细长附属物，纤毛和鞭毛，虽然我们的重点是后者。虽然鞭毛超微结构在原核生物和真核生物之间存在差异，但统一和基本的微机械原理适用，因此鞭毛细胞生物学的不同领域受到相同的基础力学的支配。这种机制的重要性是例证表面游泳-至关重要的了解细菌的行为在表面殖民化，从而生物膜启动以及精子细胞与微器件和女性生殖道的表面相互作用。进一步的例子包括鞭毛的控制和调节，以及为什么它会采用任何给定的节拍模式，对此有许多思想流派，但很少有机械分析，尽管后者在完善我们的理解方面很有用。这个理论项目的战略目标将是通过数学建模和计算机模拟进一步发展我们对鞭毛虫运动的机械理解。具体而言，该项目旨在开发新的软件，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。这将通过对不同微生物中鞭毛调控的理论研究来补充，研究该领域最近的假设，并旨在通过考虑其他结构特征来扩展当前的理解。一个例子是研究原生寄生虫利什曼原虫属运动的机械原理，利什曼原虫每年感染多达100万人。第一项研究的目的将是了解和理解利什曼原虫运动的各个方面，例如细胞被鞭毛沿着拖动而不是推动的事实，以及细胞体与其他鞭毛动物相比非常大的事实，在其生命周期的游泳阶段对其行为的影响。这包括表面游泳行为，与上皮附着和脱离，而寄生虫是居住在其宿主，白蛉。它还包括这些细胞在背景流中的行为，这与人类感染的初始阶段的寄生虫的血流形式有关，并且利什曼原虫行为的两个方面都没有受到详细的机械分析和计算机模拟。还将探讨与牛津大学邓恩病理学院的伊娃格伦茨和理查德惠勒博士合作进行其他研究的前景，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在生物学文献和生物学同事中对鞭毛调节的假设机制进行机械分析。一个例子是真核生物鞭毛内的空间异质性分子马达刚性是否解释了在被称为超活化的过程中鞭毛的不对称性，该过程已被观察到是哺乳动物自然受精所必需的。这些后者的研究还需要进一步发展的细丝弹性流体动力学模拟，因此，除了生物和建模的新奇，这样的研究也将是新颖的，从计算物理学的观点。因此，该项目属于EPSRC研究领域的福尔斯（i）数学生物学（ii）流体动力学和（iii）连续介质力学。

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.