Nonequilibrium Physics of Spindle Assembly: Understanding the Response of the Spindle to Perturbations

该奖项资助了哈佛大学 Daniel Needleman 教授指导下的一个研究项目。当细胞分裂时，它的每个子细胞都必须获得其 DNA 的完整副本。 首先，DNA 被复制，然后 DNA 的两个拷贝通过一种高度复杂的自组织结构（称为纺锤体）分离到子细胞中。 虽然主轴的许多部件已经被详细研究，但对于主轴如何组装和执行其功能仍然知之甚少。 了解纺锤体等自组织结构不仅对生物学至关重要，而且对物理学提出了根本性挑战，因为这些系统是生命材料，其行为与凝聚态物理学中传统研究的惰性物质截然不同。 在这个项目中，尼德曼教授将采用物理学方法，包括定量实验和数学理论，来理解主轴。 这项研究的目标是开发和测试可能解释纺锤体对药物以及生化和物理扰动的反应的理论。该项目预计将产生更广泛的影响。了解纺锤体对扰动的反应可能具有医学益处，因为纺锤体功能的错误被认为会导致一些癌症和出生缺陷，并且许多化疗药物通过干扰纺锤体发挥作用。从定量角度研究纺锤体还可以为非平衡统计力学提供基本见解，提高我们对生命物质的理解，并提高设计新材料的能力。 从事该项目的本科生和研究生将接受高度跨学科的培训。 通过该研究项目获得的结果也将在研究期刊和实验室网站上传播。 将开发并使用针对高中、本科生和研究生水平学生的课程材料，以促进针对更广泛受众的跨学科培训。 Needleman 教授还将在与高中教师的接触和鼓励高中生追求 STEM 职业方面发挥积极作用。

This award funds a research project under the direction of Professor Daniel Needleman at Harvard University.When a cell divides, each of its daughter cells must receive a complete copy of its DNA. First the DNA is duplicated, and then the two copies of DNA are segregated into the daughter cells by a highly complex, self-organizing structure called the spindle. While many of the components of the spindle have been studied in detail, there is still very little known about how the spindle assembles and carries out its function. Understanding self-organizing structures such as the spindle is not only crucial for biology, but also poses a fundamental challenge for physics, since these systems are living materials that behave drastically differently from the inert matter that has been traditionally studied in condensed matter physics. In this project, Professor Needleman will employ approaches from physics, including quantitative experiments and mathematical theories, to understand the spindle. The goal of this research is to develop and test theories that might explain the responses of the spindle to drugs and to biochemical and physical perturbations.This project is envisioned to have significant broader impacts. Understanding the response of the spindle to perturbations may have medical benefits, as errors in spindle function are believed to cause some cancers and birth defects, and many chemotherapy agents work by interfering with the spindle. Studying the spindle from a quantitative perspective may also provide fundamental insights into nonequilibrium statistical mechanics, improve our understanding of living matter, and lead to the ability to design new materials. Undergraduate and graduate students working on this project will receive highly interdisciplinary training. The results obtained through this research project will also be disseminated in research journals and on the lab web site. Course material for students at the high school, undergraduate, and graduate levels will be developed and used to promote interdisciplinary training for a wider audience. Professor Needleman will also take an active role in outreach to high school teachers and in encouraging high school students to pursue STEM careers.