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。细胞分裂平面在胞质分裂中的定位是一个基本和普遍的细胞过程，与细胞的形态发生、发育、组织结构和干细胞有着广泛的相关性。这项研究的目的是确定控制这一过程的分子机制。该项目利用海胆胚胎作为一种有效的动物细胞模型进行对称细胞分裂。细胞分裂部位的确定涉及多个过程。细胞最初在间期晚期沿着可复制的轴相对于其细胞形状定位和定向细胞核。在这个过程中，细胞核必须以某种方式感觉到细胞的形状。间期核的轴线确定了有丝分裂中纺锤体的位置，然后确定了胞质分裂中的分裂位置。该项目将重点研究细胞核如何定位、细胞形状如何感知以及纺锤体如何向皮质发出信号以指定分裂平面的机制。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)的微型制造的腔中，通过操纵海胆细胞的形状来系统地研究细胞几何的影响。该项目将包括活细胞实验，重点是识别负责核定位的特定分子马达的位置和特定分子马达，以及计算模型如何在被操纵成不同形状的细胞中确定分裂平面。广泛的影响：研究人员继续长期努力，通过扩大科学中代表性不足的少数群体的参与，增加科学家的多样性。工作将在实验室和国家活动中进行。PI是一名细胞生物学家，也是一名美洲原住民(切诺基人)，他长期参与与不同学生群体的合作和国家计划努力。研究人员每年夏天在伍兹霍尔海洋生物实验室共用一个实验室，在那里他们接待从波士顿学院和美国原住民科学促进会(SACNAS)年会上在全国范围内招募的本科生(主要来自代表不足的群体)，以及来自NSF资助的MBL REU暑期项目的本科生。这些学生被指导参加一些活动，这些活动的目的是为了更好地装备他们，如果他们选择从事科学职业的话。在国家层面，PI继续在旨在增加科学家多样性的项目中发挥领导作用，包括领导NSF支持的SACNAS、美国细胞生物学学会的工作，并定期为AAAS、NSF以及学院、大学和科学学会服务，以实现政策变化、评估计划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. The PI 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 Marine Biology Laboratory, 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.