Almost all eukaryotic cells use actins for multiple vital processes. Cells move, divide, organize their interior, and establish and maintain their shape with the help of actins filaments. Repeated, identical subunits similar across cell types make up these filaments. Despite the common nature of the filaments, cells co-opt them for multifarious tasks with a spectrum of proteins to nucleate, cap, sever, branch, cross-link, and move along them. This work aims both (i) to understand how cells employ actins for specific tasks and (ii) to push our understanding of the actins system towards a physical picture expressed by predictive mathematical models. This study focuses on fission yeast as a model eukaryotic cell. The proposed approach combines mathematical modeling, image analysis, and experimental biology to study how cells organize actins. Two hypotheses form the basis of the study. First, that cross-linking proteins aid the formation of a ring that divides the cytoplasm during the final step of division. Second, that nucleating proteins and severing proteins act in concert with confinement to organize actins into cables. The study proposes to test these hypotheses by (i) extracting relevant quantities from micro- scope images of these structures, (ii) building mathematical models of these structures emphasizing measurable quantities, and (iii) collaborating with experimentalists to subject these models to rigorous challenges. The image analysis uses novel tools, such as tools for automated filament and filament-network tracking, developed in collaboration with computer scientists. The mathematical modeling makes use of a combination of discrete and continuum approaches to dynamical systems informed by experimental parameters. The experimental chal- lenges come in collaboration with Jian-Qiu Wu's lab and in the form of genetic manipulations, pharmacological treatments, and fluorescence microscopy. Every aspect of the study leads to a mechanistic understanding of the actins cytoskeleton and its roles that would underpin future cancer and health research based on an advanced understanding of cellular function.
This project uses mathematical modeling, image analysis, and experimental biology to study the actins cy- toskeleton, a dynamic structure underlying the growth and division of all human cells. If successful, this basic science would underpin future cancer and health research based on an understanding of cellular function.
|Khalili, Bita; Merlini, Laura; Vincenzetti, Vincent et al. (2018) Exploration and stabilization of Ras1 mating zone: A mechanism with positive and negative feedbacks. PLoS Comput Biol 14:e1006317|
|Merlini, Laura; Khalili, Bita; Dudin, Omaya et al. (2018) Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating. J Cell Biol 217:1467-1483|
|Zhang, Tian; Vavylonis, Dimitrios; Durachko, Daniel M et al. (2017) Nanoscale movements of cellulose microfibrils in primary cell walls. Nat Plants 3:17056|
|Ryan, Gillian L; Holz, Danielle; Yamashiro, Sawako et al. (2017) Cell protrusion and retraction driven by fluctuations in actin polymerization: A two-dimensional model. Cytoskeleton (Hoboken) 74:490-503|
|Wan, Sunhua; Lee, Hsiang-Chieh; Huang, Xiaolei et al. (2017) Integrated local binary pattern texture features for classification of breast tissue imaged by optical coherence microscopy. Med Image Anal 38:104-116|
|Merlini, Laura; Khalili, Bita; Bendezú, Felipe O et al. (2016) Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating. Curr Biol 26:1117-25|
|Zhang, Dan; Bidone, Tamara C; Vavylonis, Dimitrios (2016) ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly. Curr Biol 26:647-53|
|McMillen, Laura M; Vavylonis, Dimitrios (2016) Model of turnover kinetics in the lamellipodium: implications of slow- and fast- diffusing capping protein and Arp2/3 complex. Phys Biol 13:066009|
|Heisler, David B; Kudryashova, Elena; Grinevich, Dmitry O et al. (2015) ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization. Science 349:535-9|
|Vitriol, Eric A; McMillen, Laura M; Kapustina, Maryna et al. (2015) Two functionally distinct sources of actin monomers supply the leading edge of lamellipodia. Cell Rep 11:433-45|
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