Collective dynamics in cell clusters

细胞簇中的集体动力学

• 批准号: 10733920
• 负责人: Stanislav Y. Shvartsman
• 金额: $ 33.37万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733920
• 关键词: 3-Dimensional; Active Biological Transport; Address; Animals; Biology; Cell Count; Cell Cycle Arrest; Cell Lineage; Cells; Clinical; Computer Models; Coupling; Cytoplasm; Cytoplasmic streaming; Cytoskeleton; Data; Deposition; Development; Diffusion; Drosophila genus; Embryo; Embryonic Development; End Point Assay; Experimental Models; Fertility; Fertility Disorders; Filament; Funding; Future; Gametogenesis; Genetic; Genetic Models; Genetic Transcription; Germ; Germ Cells; Growth; Human; Image; Interdisciplinary Study; Joints; Kinesin; Mediating; Microtubules; Mitotic; Modeling; Motor; Nature; Oocytes; Oogenesis; Process; Proteins; Regulation; Relaxation; Reproduction; Reproductive Biology; Research; Research Personnel; Research Support; Resources; Signal Transduction; Somatic Cell; Speed; Structure of primordial sex cell; Study models; Supporting Cell; System; Testing; Theoretical Studies; Training; Walking; Work; biophysical model; computer studies; computerized tools; data tools; design; egg; experimental study; fluid flow; hydrodynamic flow; image processing; imaging study; insight; model organism; scientific computing; statistics; theories; tumor

Abstract The proposed work will combine experiments and theory to advance quantitative understanding of animal gametogenesis. We use Drosophila as a genetic model organism that is highly suitable for quantitative interdisciplinary research and focus on two evolutionarily conserved aspects of reproductive biology. First, eggs and early embryos of large volumes require efficient means for coordinating cytoplasmic processes. Studies in multiple experimental systems indicate that such coordination in large cells relies on large-scale hydrodynamic flows, which reach the speeds of 100s nm/s and can mediate rapid mixing and transport of cytoplasmic components. Our Aim 1 investigates such flows at a critical point in Drosophila oogenesis, where cytoplasmic streaming is driven by cargo-loaded kinesin motors walking on arrays of cortically anchored microtubules. We will use computational modeling and live imaging to systematically test a recent theory according to which cytoplasmic streaming emerges spontaneously, through hydrodynamic coupling of cortically anchored microtubules. Second, gametogenesis in both Drosophila and humans starts with the formation of cell-cycle arrested primordial germ cells (PCSs). Quantitative control of PGC numbers is essential for organismal fertility and for avoiding germline tumors. Aim 2 will investigate quantitative control of PGCs numbers in Drosophila embryos, where PGCs are formed by limited divisions of the pole cells, the first true cells to form in the embryo. We will use live imaging to characterize statistics of pole cell lineages and test the hypothesis that control of PGC numbers can be explained using a model in which a mitotic clock slowly drifts out of an oscillatory regime. Given the ubiquitous nature of cytoplasmic flows and conserved mechanisms of PGC regulation, our results will have broad impact by providing answers to fundamental questions of developmental and reproduction biology.

摘要

项目成果

Clonal dominance in excitable cell networks.

• DOI: 10.1038/s41567-021-01383-0
• 发表时间: 2021-12
• 期刊: Nature physics
• 影响因子: 19.6
• 作者: Alsous JI;Rozman J;Marmion RA;Košmrlj A;Shvartsman SY
• 通讯作者: Shvartsman SY

Mechanics of stabilized intercellular bridges.

稳定细胞间桥的力学。

• DOI: 10.1016/j.bpj.2022.06.033
• 发表时间: 2022
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Singh,Jaspreet;ImranAlsous,Jasmin;Garikipati,Krishna;Shvartsman,StanislavY
• 通讯作者: Shvartsman,StanislavY

Author Correction: Forced and spontaneous symmetry breaking in cell polarization.

作者更正：细胞极化中的强迫和自发对称性破缺。

• DOI: 10.1038/s43588-022-00345-7
• 发表时间: 2022
• 期刊: Nature computational science
• 作者: Miller,PearsonW;Fortunato,Daniel;Muratov,Cyrill;Greengard,Leslie;Shvartsman,Stanislav
• 通讯作者: Shvartsman,Stanislav

Forced and spontaneous symmetry breaking in cell polarization.

• DOI: 10.1038/s43588-022-00295-0
• 发表时间: 2022-08
• 期刊: NATURE COMPUTATIONAL SCIENCE
• 作者: Miller, Pearson W.;Fortunato, Daniel;Muratov, Cyrill;Greengard, Leslie;Shvartsman, Stanislav
• 通讯作者: Shvartsman, Stanislav

Deconstructing gastrulation at single-cell resolution.

• DOI: 10.1016/j.cub.2022.02.059
• 发表时间: 2022-04-25
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Stern, Tomer;Shvartsman, Stanislav Y.;Wieschaus, Eric F.
• 通讯作者: Wieschaus, Eric F.