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

此次美国-荷兰项目开发访问将促进位于阿姆赫斯特的马萨诸塞大学国际和平研究所的实验小组和位于阿姆斯特丹的VU大学的弗雷德·麦金托什教授的理论小组之间的新合作。利用PI在细胞分裂过程中染色体/纺锤体运动的实验数据，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搭建一座从理论模型到具有生物学意义的结果的桥梁，以推进我们对染色体在细胞分裂过程中如何运动的基本理解。有了初步的结果，合作伙伴希望建立一个理论和定量框架，来表征和帮助解释活细胞核微环境的机制。一名美国研究生参与这项活动将提供宝贵的职业生涯早期研究经验，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，这些发现将有助于我们解决目前定量细胞内微观流变学带来的挑战，并为美国-荷兰团队的长期研究奠定基础。生物体从胚胎到老年的生长来自细胞分裂。它是生物体生物学的一个基本部分，在这个过程中获得一个适当的染色体运动模型有助于理解这一基本事件。在阿姆斯特丹的研究访问期间，将从理论上分析美国关于荧光探针(在细胞核中和在核机械环境中活动的体外最小模型中)非平衡运动的实验结果。合作努力将集中在波动增强的频率依赖性和探针大小的依赖性上，这些探针附着在染色体上或跨越整个纺锤体。这些关于凝聚的DNA在活细胞和体外的动态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，以及它在DNA在细胞核中的行为方式中所起的作用。

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.