Collaborative Research: BIOMAPS Control of Spindle Positioning and Cytokinesis

智力优势：细胞通常在一个特定的、可预测的位置分裂。细胞分裂过程中细胞分裂平面的定位是一个基本的和普遍的细胞过程，与细胞形态发生、发育、组织结构和干细胞有广泛的关系。本研究的目的是确定控制这一过程的分子机制。本项目利用海胆胚胎作为对称细胞分裂的有效动物细胞模型。细胞分裂位点的确定涉及多个过程。细胞最初在间期晚期，细胞核沿着相对于其细胞形状的可复制轴定位和定向。在这个过程中，细胞核必须以某种方式感知细胞的形状。间期核的轴确定有丝分裂时纺锤体的位置，然后确定细胞质分裂时分裂的位置。该项目将重点研究细胞核如何定位的机制，细胞形状如何被感知，以及纺锤体如何向皮层发出信号以指定分裂平面。研究人员最近开发了一种强大的新方法，通过将海胆细胞引入不同形状（如矩形、三角形等）的微型制造室来操纵细胞的形状，以系统的方式研究细胞几何形状的影响。该项目将包括活细胞实验，重点是确定负责核定位的特定分子马达的位置，以及如何在被操纵成不同形状的细胞中确定分裂平面的计算建模。更广泛的影响：研究人员通过扩大未被充分代表的少数群体在科学领域的参与，继续长期努力增加科学家的多样性。将在实验室和国家活动两方面作出努力。参与这个合作项目的PI之一是一位细胞生物学家，他也是一位印第安人（切诺基人），长期以来，他参与了与不同学生群体的合作和国家项目的努力。研究人员每年夏天在伍兹霍尔MBL的一个实验室里共享大约两个月的时间，在那里他们招收本科生（主要来自代表性不足的群体），这些本科生来自波士顿学院的奇卡诺人和美洲原住民科学进步协会（SACNAS）年会，以及MBL的国家科学基金会资助的REU暑期项目。这些学生被指导参加一些活动，其目的是更好地装备他们，如果他们选择追求科学事业。在国家层面，PI继续在项目中发挥领导作用，其目标是增加科学家的多样性，包括领导NSF支持的SACNAS、美国细胞生物学学会的工作，并通过服务于AAAS、NSF、学院、大学和科学社团，以常规的身份影响政策变化、评估项目，并为国家活动做出贡献。

Intellectual Merit: Cells typically divide at a specific, predictable location. Positioning of the cell division plane in cytokinesis is a fundamental and universal cellular process that has broad relevance to cell morphogenesis, development, tissue architecture, and stem cells. The aims of this research are to determine the molecular mechanisms governing this process. This project utilizes the sea urchin embryo as a potent animal cell model for symmetric cell division. Cell division site determination involves multiple processes. The cell initially positions and orients the nucleus in late interphase along a reproducible axis relative to its cell shape. In this process, the nucleus must somehow sense the shape of the cell. The axis of the interphase nucleus sets the position of the spindle in mitosis, which then specifies the site of cleavage in cytokinesis. The project will focus on the mechanisms of how the nucleus is positioned, how cell shape is sensed, and how the spindle signals to the cortex to specify the division plane. The researchers have recently developed a powerful new approach to study the effect of cell geometry in a systematic manner by manipulating the shape of sea urchin cells by introducing them into micro-fabricated chambers of different shapes (such as rectangles, triangles, etc. The project will include live cell experiments focusing on the identifying the location of and specific molecular motor responsible for nuclear positioning coupled with computational modeling of how the division plane is determined in cells manipulated into different shapes.Broader Impacts: The researchers continue longstanding efforts to increase the diversity of scientists by broadening participation of underrepresented minorities in science. Efforts will be directed both in the laboratory and in national activities. One of the PI's on this collaborative project is a cell biologist who is also a Native American (Cherokee) who has a long record of involvement in working with a diverse pool of students and in national programmatic efforts. The researchers share a laboratory at the MBL, Woods Hole for about two months each summer where they host undergraduates (mostly from underrepresented groups) recruited nationally at the Society for Advancement of Chicanos and Native Americans in Science (SACNAS) annual conference, from Boston College, and from the NSF funded REU summer program at the MBL. These students are mentored to participate in a number of activities whose aim is to better equip them, should they choose to pursue a scientific career. At the national level, the PI is continuing in a leadership role in programs whose goal is to increase the diversity of scientists including leading NSF supported efforts for SACNAS, for the American Society for Cell Biology and serving in a regular capacity to effect policy change, evaluate programs, and contribute to national activities by service to the AAAS, the NSF, and to colleges, universities and scientific societies.