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|Title:||Symmetry Breaking in Cells & Cell Networks|
|Advisors:||Shvartsman, Stanislav Y|
|Contributors:||Chemical and Biological Engineering Department|
|Publisher:||Princeton, NJ : Princeton University|
|Abstract:||Proper development and growth of all organisms requires biological decisions that are precisely defined spatially and temporally. In many cases, these processes arise from the breaking of some symmetry, creating new structures essential for continued development. Despite their importance, we have until recently lacked the proper advanced quantitative imaging techniques and image processing algorithms necessary to analyze and explore these key developmental structures. In addition to experimentally-derived measurements and high-level quantification of these events, mathematical models provide a systematic approach for analyzing these processes, revealing key insights into robustness based on properties of the organism itself. Using these approaches, we focus on three key symmetry breaking events in cells and cell networks: single cell polarization, oocyte selection, and emergence of growth patterns in multicellular clusters. In the first case, we aim to understand how cell shape affects the membrane localization of proteins, an essential step in the development and reproduction of many organisms. Using numerical simulations as a guide, we provide analytical solutions for constructing high concentration protein patches based on the redistribution of proteins between the cell surface and bulk of domains of a sphere, an important precursor for exploring curvature-driven pattern formation in cells. Furthermore, through experimental, mathematical, and computational approaches, we investigate how one cell is selected to become the future oocyte and how the corresponding cluster of interconnected cells grows collectively throughout development. Both oocyte selection and the growth of multicellular structures involve the exchange of proteins and organelles across cells through a network of reinforced cytoplasmic channels. While the formation and structure of this class of multicellular systems has been extensively studied, their dynamics are poorly understood, leaving many critical questions about cell fate determination and development unanswered. Our findings provide new insights into aspects of gametogenesis and growth dynamics present across species. In addition, we demonstrate how the tools developed throughout these studies may be applied to quantify early developmental events in other contexts.|
|Alternate format:||The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu|
|Type of Material:||Academic dissertations (Ph.D.)|
|Appears in Collections:||Chemical and Biological Engineering|
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