Science and Technology Center for Quantitative Cell Biology

定量细胞生物学科学技术中心（QCB）旨在通过创建全细胞模型来彻底改变我们对细胞的理解，这些模型忠实地捕捉细胞功能和紧急行为的各个方面。QCB将利用计算、人工智能和超分辨率成像的最新进展，以及最先进的组学和细胞测量技术，开发具有新颖细节和预测能力的模型。最终，QCB渴望解开活细胞的秘密，预测正常和异常的细胞功能，设计单细胞和多细胞系统，为人类健康、气候变化和农业提供解决方案，推动美国生物经济。QCB的教育，扩大参与和知识共享计划将确保多样化的劳动力在定量细胞生物学方面得到良好的培训。该中心的目标是将研究细胞关键“模块”的实验学家社区与计算科学家社区聚集在一起，计算科学家社区将建立一个统一的细胞模型，包括在环境影响下真核和细菌细胞的所有基本过程，包括基因表达，代谢和分裂。统一模型有可能对每一个模型生物化学物种的随时间变化的行为做出预测——这相当于同时进行数百次实验的数据量。尝试把我们从分子生物学、化学和物理学中获得的综合知识综合成一个完整的细胞模型的时机已经成熟。在技术方面，伊利诺伊大学厄巴纳-香槟分校（University of Illinois at Urbana-Champaign）在跟踪单个分子方面有着悠久的历史，并且是使用最小光子通量（MINFLUX）显微镜定位生物分子到2纳米空间分辨率的合作采用者，并在活细胞的背景下以100微秒的时间分辨率跟踪它们。MINFLUX比所有其他现有的单分子技术改进了10倍，与结构电子显微镜和红外代谢组学技术建立了动态联系。在细胞生物学方面，细胞“模块”的例子有：在细胞内运输货物时的分子马达，通过细胞核内rna -蛋白质转录复合物的组装形成剪接体，基因表达过程中染色体动力学和与核凝聚物的相互作用，细胞器网络从健康状态转变为不健康状态时的变化，真核和细菌细胞及其细胞器网络的相互作用。MINFLUX研究的这些细胞动力学过程将辅以低温电子显微镜（CEM）对大型功能中间体/复合物的测量，以及分子动力学和粗粒度模拟来确定基本的机制状态。动态红外显微镜将聚焦于细胞内经常被忽视的小代谢物。低温电子断层扫描（CET）捕获的整个细胞区域将作为细胞模拟中超微结构的基础，其空间分辨率为8-32纳米，时间步长为50-100微秒。反应-扩散过程的细胞模拟将代谢动力学与从MINFLUX测量中获得的遗传信息过程的动力学相结合，以创建从分子水平到细胞分裂的细胞功能的统一模型。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Science and Technology Center for Quantitative Cell Biology (QCB) aims to revolutionize our understanding of cells via the creation of whole-cell models that faithfully capture all aspects of cell function and emergent behavior. QCB will leverage the newest advances in computing, artificial intelligence, and super-resolution imaging, as well as the state of the art -omics and cellular measurements, to develop models with novel details and predictive capabilities. Ultimately, QCB aspires to unlock the secrets of living cells, to predict normal and abnormal cellular functions, and to design single cells and multicellular systems that provide solutions for human health, climate change and agriculture, fueling the U.S. bioeconomy. QCB’s education, broadening participation, and knowledge sharing programs will ensure that a diverse workforce is well-trained in quantitative cell biology. The goal of this center is to bring together a community of experimentalists who will study key “modules” of the cell with a community of computational scientists who will build a unified model of the cell, comprising all fundamental processes, including gene expression, metabolism, and division, for both eukaryotic and bacterial cells under the influence of their environment. Unified models have the potential to make predictions of the time-dependent behavior for every modeled biochemical species – a quantity of data akin to performing hundreds of simultaneous experiments. The time is ripe for attempting a synthesis of the comprehensive knowledge we have from molecular biology, chemistry, and physics into a complete model of the cell. On the technology side, the University of Illinois at Urbana-Champaign has a strong history of tracking single molecules, and is a collaborative adopter of a facility that uses minimal photon fluxes (MINFLUX) microscopy to locate biomolecules to 2 nanometer spatial resolution and track them with 100 microsecond time resolution within the context of a living cell. MINFLUX represents a 10-fold improvement over all other existing single-molecule techniques, making the dynamical connection with structural electron microscopy and IR metabolomics techniques. On the cell biology side, examples of “modules” of the cell are molecular motors as they transport cargo across the cell, formation of spliceosomes through assembly of RNA-protein transcriptional complexes within the nucleus, chromosome dynamics and interactions with nuclear condensates during gene expression, changes in organelle networks as they transition from healthy and to unhealthy states, and interactions of eukaryotic and bacterial cells and their organelle networks. These cellular dynamical processes studied by MINFLUX will be complemented by cryogenic electron microscopy (CEM) measurements of large functional intermediates/complexes, and molecular dynamics and coarse-grained simulations to determine essential mechanistic states. Dynamical infrared microscopy will focus on the often-neglected small metabolites inside cells. Regions of the entire cell captured by cryogenic electron tomography (CET) will serve as the basis for the ultrastructure in cell simulations, with resolutions ranging from 8-32 nanometers in space and 50-100 microsecond time steps. Cell simulations of the reaction-diffusion processes will integrate metabolic kinetics with the dynamics of genetic information processes obtained from MINFLUX measurements to create a unified model of cellular function, from the molecular level up to cell division.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.