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

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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.