Collaborative Research: BIOMAPS Control of Spindle Positioning and Cytokinesis

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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.