A biophysical study on how the actin and microtubule cytoskeletons dynamically collaborate to regulate cellular organization

生物学中的一个基本问题是复杂的动物是如何从第一个细胞--卵子--起源的。很久以前，胚胎学家就提出，卵子细胞质中被称为决定簇的物质的不对称分布（称为卵子极化）可以赋予细胞分裂时接收它们的细胞一种特定的特征。在果蝇中发现了卵子极化的一个最显著的例子，在卵子发生过程中，各种决定因素的不对称定位建立了身体计划。为了使这些发展决定因素适当地定位，需要发生各种复杂的过程。首先，细胞（如鸡蛋）不是对称实体;相反，它们必须采用特定的不对称性，这对于定义决定因素的最终位置至关重要。此外，决定子所通过的液体，即细胞质，并不是静止的。相反，它是一种旋转的、喷射的、动态的流体。因此，要理解物质的不对称分布是如何实现的，我们不仅需要研究物质的运动，还需要研究围绕物质的高度动态的细胞质的运动。分子运动和细胞质流体动力学之间的联系不仅是理论上的，而且是机械上的。细胞具有两种复杂的丝状结构，称为肌动蛋白和微管（MT）细胞骨架，它们施加力并驱动分子和细胞器的运输。这些细胞骨架和一组沿着它们“行走”的蛋白质（称为分子马达）不仅需要运输决定簇，还需要诱导细胞质流动。有时肌动蛋白，MT和它们的马达蛋白作为单独的系统，但也有经常了解两个细胞骨架之间的串扰。在果蝇雌性生殖系中，发育决定因素的定位由肌动蛋白、MT和运动蛋白驱动蛋白之间的相互作用决定。定向运输和细胞质流动都是由这种相互作用介导的。这构成了一个强大的细胞组织模型的发展的重要性，其中两个细胞骨架动态相互调节。我们将采用统一的理论和实验方法来了解肌动蛋白和MT细胞骨架如何协调卵子发生过程中的基本和发育调节的不对称性和运动。此外，我们将探讨流如何影响细胞骨架的组织，以及流揭示了什么样的潜在力量。具体来说，我们将研究：1。细胞质流动和MT细胞骨架之间的双向联系;和2。肌动蛋白细胞骨架对流动、MT和驱动蛋白的调节。

A fundamental question in biology is how complex animals originate from the first cell, the egg. Embryologists suggested long ago that the asymmetric distribution of substances, called determinants, in the cytoplasm of an egg (known as egg polarization) could confer a specific characteristic to the cells that receive them upon cell division. One of the most striking examples of egg polarization is found in Drosophila, in which the asymmetric localization of various determinants during oogenesis establishes the body plan. For these developmental determinants to localize properly, a variety of complex processes need to take place. Firstly, cells (such as the egg) are not symmetric entities; rather they have to adopt particular asymmetries, which are critical to define the final position of the determinants. Additionally, the fluid through which the determinants navigate, known as cytoplasm is not quiescent. Instead it is a swirling, jetting, dynamic fluid. Thus, to understand how the asymmetric distribution of substances is achieved, we need to study not only the movement of the substance, but also the motion of the highly dynamic cytoplasm that surrounds the substance.The link between the movement of molecules and the fluid dynamics of the cytoplasm is not only a theoretical one, but also a mechanistic one. Cells have two complex filamentous structures, known as the actin and microtubule (MT) cytoskeletons that exert forces and drive transport of molecules and organelles. These cytoskeletons, and a group of proteins (known as molecular motors) that "walk" along them, are required to transport determinants, but also to induce cytoplasmic flows. At times actin, MTs and their motor proteins act as separate systems, but there is also often poorly understood crosstalk between the two cytoskeletons. In the Drosophila female germline, localization of developmental determinants is governed by the interplay among actin, MTs and the motor protein Kinesin. Both directed transport and cytoplasm streaming, are mediated by this interplay. This constitutes a powerful cellular organization model of developmental importance in which the two cytoskeletons dynamically modulate each other. We will employ a unified theoretical and experimental approach to understand how the actin and MT cytoskeletons coordinate the essential, and developmentally regulated, asymmetries and motions during oogenesis. Further, we will explore how streaming impacts on the organization of the cytoskeletons, and what flows reveal about the underlying forces. Specifically, we will investigate: 1. The bi-directional link between cytoplasmic flows and the MT cytoskeleton; and 2. The regulation of streaming, MTs and Kinesin by the actin cytoskeleton.