CNIC: U.S.-Netherlands Project Development of Experimental and Theoretical Tools to Investigate the Non-equilibrium Mechanics of the Cell Nucleus

这个美国-荷兰项目开发访问将促进PI在阿默斯特马萨诸塞州大学的实验小组与阿姆斯特丹VU大学的Fred MacKintosh教授的理论小组之间的新合作。 与PI的细胞分裂过程中的染色体/纺锤体运动实验数据一起工作，将共同开发新的理论模型来解释她的数据并扩展UV大学的主动网络模型。 这项新合作的目标是建立一座从理论模型到结果的桥梁，并具有生物学意义，以促进我们对染色体在细胞分裂过程中如何移动的基本理解。 通过初步结果，合作伙伴希望建立一个理论和定量框架，以表征和帮助解释活细胞核微环境的力学。一名美国研究生参与这项活动将提供宝贵的早期职业研究经验，包括实验和理论方法，以及接触一系列生物物理系统和方法，包括先进的显微镜。 如果成功的话，这些发现将有助于我们应对定量细胞内微观流变学目前所带来的挑战，并为美国的研究奠定基础。荷兰研究小组的长期研究。生物体从胚胎到老年的生长都是通过细胞分裂进行的。 它是生物体生物学的一个基本组成部分，在这个过程中获得染色体运动的适当模型有助于理解这一基本事件。 在对阿姆斯特丹的研究访问期间，将对美国关于荧光探针非平衡运动的实验结果（在细胞核中和在核机械环境中活性的体外最小模型中）进行理论分析。 合作的努力将集中在波动增强的频率依赖性和依赖于探针的大小尺度，连接到染色体位点或跨越整个纺锤体。 这些关于浓缩DNA在活细胞和体外的动力学行为的实验和理论可能会导致一种新的方式来思考活细胞中的生命运动及其在DNA在细胞核中的行为方式中的作用。

This U.S.-Netherlands project development visit will catalyze new collaboration between the PI's experimental group at the University of Massachusetts, Amherst, and the theoretical group of Prof. Fred MacKintosh at the VU University, in Amsterdam. Working with the PI's data from experiments on chromosomal/spindle motion during cell division, new theoretical models will be developed jointly to interpret her data and extend UV University's active network models. The goal of the new collaboration is to ceate a bridge going from theoretical models to results with biological implications for advancing our basic understanding of how chromosomes move during cell division. With preliminary results, the partners expect to establish a theoretical and quantitative framework to characterize and help explain the mechanics of the microenvironment of the living cell nucleus. Involvement of one U.S. graduate student in this activity will provide valuable early career research experience with both experimental and theoretical approaches, as well as exposure to a range of biophysical systems and methods, including advanced microscopy. If successful, findings should contribute to our ability to address the challenges currently posed by quantitative intracellular microrheology and prepare a foundation for the U.S.-Netherlands team's longer term research.Growth in organisms, from embryo to old age, proceeds from cell division. It is a fundamental part of the biology of organisms and obtaining an appropriate model for the motion of chromosomes during the process could help with understanding of this basic event. During research visits to Amsterdam, U.S. experimental results on the nonequilibrium motions of fluorescent probes (in the cell nucleus and in an in vitro minimal model for activity in the nuclear mechanical environment) will be analyzed theoretically. Cooperative efforts will focus on the frequency dependence of the fluctuation enhancement and the dependence on the size scale of the probes, attached to a chromosome locus or spanning the entire spindle. These experiments and theory on the dynamic behavior of condensed DNA in living cells and in vitro could lead to a new way of thinking about the vital motion in living cells and about its role in the way DNA behaves in the nucleus.