RoL-FELS:RAISE: Specialization and decision making among synctial nuclei

RoL-FELS：RAISE：合核之间的专业化和决策

• 批准号: 1840273
• 负责人: Amy Gladfelter
• 金额: $ 100万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1840273&HistoricalAwards=false
• 关键词: RoL; FELS; RAISE; Specialization; decision

Cells containing multiple nuclei (syncytial cells) are common across the entire tree of life and are found in every biosphere from bone, muscle, placenta and embryos of animals to the complex networks formed by fungi, water- and slime-molds. Yet little is known about the advantages an organism receives from having multinucleated cells, or how multiple nuclei communicate and coordinate to control cell behavior. This project will use biological and mathematical tools to test whether and how nuclei within multinucleate cells of the filamentous fungus Neurospora crassa adopt different roles in response to changes in the fungus' environment - allowing for a flexible division of labor within the cell. In addition to revealing general rules for nuclear coordination, the project has potential to enhance fungal productivity for food production and biotechnology. The project will offer graduate and undergraduate students interdisciplinary training in mathematical modeling, cell biology, genetics and novel microscopic imaging technology. In addition, new K-12 outreach activities will be catalyzed, including training of teachers and creation of new lesson plans on real world applications of mathematics and the utility of quantitative analysis in biology. Finally, the syncytial cell research community will be stimulated by a workshop that brings together mathematicians and scientists studying multinucleate cells in diverse organisms, including fungi.Multinucleate cells allow the proportion of nuclei that contribute to any specific function to be dynamically tuned according to cellular requirements. But such division of labor is impossible if nuclei that share cytoplasm also see identical proteins and environmental cues. So, for nuclei to behave autonomously, protoplasm must be organized to control communication between adjacent nuclei. This project will use computational imaging, genetics and mathematical modeling to study how nuclei form communities within multinucleate cells and to dissect cellular processes that control these emergent communities. The focus will be on digestion of complex carbohydrates by Neurospora crassa to: 1) analyze the adaptive costs/benefits of nuclear coordination and division of labor; 2) determine the length scales of nuclear cooperation and autonomous behaviors; and 3) develop a linked mathematical model for inter-nuclear communication and coordination, focused on identifying general mechanisms that enable nuclear communities to stably emerge from interactions of relatively few macromolecules whose abundances are dominated by Poisson noise. The project will help discover new rules of life for how coordinated behaviors emerge from autonomous nuclei in filamentous fungi, and in syncytial cells generally, within cellular compartments that range from microns to meters in size.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

包含多个核的细胞（合胞体细胞）在整个生命树中很常见，并且在每个生物圈中都可以找到，从骨骼，肌肉，胎盘和动物胚胎到由真菌，水和黏菌形成的复杂网络。然而，对于生物体从多核细胞中获得的优势，或者多个细胞核如何沟通和协调以控制细胞行为，人们知之甚少。该项目将使用生物学和数学工具来测试丝状真菌粗糙脉孢菌的多核细胞内的核是否以及如何响应真菌环境的变化而发挥不同的作用-允许细胞内灵活的劳动分工。除了揭示核协调的一般规则外，该项目还具有提高粮食生产和生物技术真菌生产力的潜力。该项目将为研究生和本科生提供数学建模，细胞生物学，遗传学和新型显微成像技术的跨学科培训。此外，还将推动新的K-12外联活动，包括培训教师和编制关于数学在真实的世界中的应用和定量分析在生物学中的效用的新教案。最后，合胞体细胞研究界将通过一个研讨会受到刺激，该研讨会汇集了研究包括真菌在内的各种生物体中多核细胞的数学家和科学家。多核细胞允许根据细胞需求动态调整有助于任何特定功能的细胞核比例。但是，如果共享细胞质的细胞核也看到相同的蛋白质和环境信号，这种劳动分工是不可能的。因此，为了让细胞核自主行动，原生质必须被组织起来，以控制相邻细胞核之间的通信。该项目将使用计算成像，遗传学和数学建模来研究细胞核如何在多核细胞内形成社区，并解剖控制这些新兴社区的细胞过程。本研究将以粗糙脉孢菌对复杂碳水化合物的消化为研究对象，分析核协调与分工的适应性成本/收益，确定核协调与自主行为的长度尺度，并对核协调与自主行为的适应性成本/收益进行分析。（3）建立核间通信与协调的关联数学模型，重点是确定一般的机制，使核社区稳定出现的相对较少的大分子的丰度由泊松噪声占主导地位的相互作用。该项目将有助于发现丝状真菌和合胞体细胞中的自主细胞核如何产生协调行为的新生命规则，这些细胞的大小从微米到米不等。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Spatial heterogeneity of the cytosol revealed by machine learning-based 3D particle tracking.

基于机器学习的 3D 粒子跟踪揭示了细胞质的空间异质性。

• DOI: 10.1091/mbc.e20-03-0210
• 发表时间: 2020
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: McLaughlin,GraceA;Langdon,ErinM;Crutchley,JohnM;Holt,LiamJ;Forest,MGregory;Newby,JayM;Gladfelter,AmyS
• 通讯作者: Gladfelter,AmyS