MPS-BIO: Collaborative Research: Physical Mechanisms Regulating Sperm Chemotaxis

MPS-BIO：合作研究：调节精子趋化性的物理机制

• 批准号: 1120200
• 负责人: Roman Stocker
• 金额: $ 43.34万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1120200&HistoricalAwards=false
• 关键词: MPS; BIO; Collaborative; Research; Physical

Despite a century of intensive research, fertilization is one of the least understood fundamental biological processes. Chemical signaling between gametes through fluid-borne cues occurs in diverse taxa with highly divergent reproductive strategies and is thought to play a fundamental role in reproduction. Still, it is unclear how chemical communication between gametes occurs under natural conditions. A critical determinant of the effectiveness of chemical cues and their influence on the motility of male gametes is ambient fluid motion. Fluid motion may promote cell interactions by bringing gametes together or alternately may inhibit adhesion and binding, yet very little is known about the effects of flow on the motility and chemotaxis of male gametes. Existing methods have limited ability to study the role of physics and chemistry in mediating gamete behavior and fertilization. It is very difficult to accurately control fluid motion and chemical cues at microscopic scales. In this project, state-of-the-art microfluidic approaches will enable unprecedented control over microenvironments naturally inhabited by gametes. This study will take a comprehensive approach and apply microfluidics to determine the roles played by physics and chemistry in gamete interactions. The proposed research, to be carried out under the guidance of PIs Jeff Riffell (U. Washington), Roman Stocker (MIT) and Richard Zimmer (UCLA), is thus structured around two principal aims: (i) determine the impact of chemical cues on male gamete motility and on fertilization success; (ii) establish the effects of fluid motion on the motility of male gametes and their response to chemical cues. The synergy and complementarity of expertise between the three PIs will enable an in-depth characterization of the biomechanics of male gamete swimming and of chemical communication between germ cells. The comprehensive and interdisciplinary approach of this study will have broad and diverse impacts on science and society. A better understanding of male gamete chemotaxis will arise from the use of microfluidic technology and provide new knowledge on reproduction and conservation biology. At the same time, the advances fostered by this study in attaining control of fluid flow and chemical cues at the microscale will provide a broad methodological framework for diverse areas of biology. The intimate combination of physics, biology and chemistry in this study will provide ample training opportunities for students at high school, undergraduate and graduate levels, emphasizing under-represented groups in science, through (1) a collaboration with the Summer Institute for Life Science (SILS) at the University of Washington, a 4-week hands-on summer institute that provides grade 4-8 teachers with research experience; (2) the development of a 3-hour science experience to be offered through MIT's Edgerton Center Outreach Program, designed for high-school students to promote hands-on experience in science; (3) the creation of a new course module at UCLA and the involvement of 3-4 UCLA undergraduates in research, each quarter; these undergraduates will be drawn from underrepresented groups through the UCLA CARE (Center for Academic and Research Excellence) and the UC LEADS (Leadership Excellence through Advanced DegreeS) Programs; and (4) the training of graduate students and postdoctorates in cell biology and microfluidics. Together, these programs will foster outreach and science education at multiple educational levels. Broad dissemination of results in technical and popular literature, in the tradition of all three PIs, will complement this outreach plan.

尽管经过一个世纪的深入研究，受精仍然是人们最不了解的基本生物过程之一。配子之间通过液体传播的化学信号发生在具有高度不同生殖策略的不同类群中，并且被认为在生殖中发挥着重要作用。尽管如此，目前还不清楚自然条件下配子之间的化学通讯是如何发生的。化学信号的有效性及其对雄配子运动的影响的一个关键决定因素是环境流体运动。流体运动可以通过将配子聚集在一起来促进细胞相互作用，或者可以抑制粘附和结合，但人们对流体对雄配子运动和趋化性的影响知之甚少。现有方法研究物理和化学在介导配子行为和受精中的作用的能力有限。在微观尺度上精确控制流体运动和化学信号是非常困难的。在这个项目中，最先进的微流体方法将能够对配子自然栖息的微环境进行前所未有的控制。这项研究将采取综合方法并应用微流体学来确定物理和化学在配子相互作用中所扮演的角色。因此，拟议的研究将在 PI Jeff Riffell（华盛顿大学）、Roman Stocker（麻省理工学院）和 Richard Zimmer（加州大学洛杉矶分校）的指导下进行，围绕两个主要目标进行：（i）确定化学线索对雄配子运动和受精成功的影响； (ii) 确定流体运动对雄配子运动及其对化学信号的反应的影响。三个 PI 之间专业知识的协同作用和互补性将能够深入表征雄配子游泳的生物力学和生殖细胞之间的化学通讯。这项研究的综合性和跨学科方法将对科学和社会产生广泛和多样化的影响。微流体技术的使用将更好地理解雄性配子趋化性，并提供生殖和保护生物学的新知识。与此同时，这项研究在微尺度上控制流体流动和化学信号方面取得的进展将为生物学的不同领域提供广泛的方法框架。这项研究将物理、生物和化学紧密结合起来，将为高中、本科和研究生水平的学生提供充足的培训机会，强调科学领域代表性不足的群体，方法是：(1) 与华盛顿大学生命科学研究所 (SILS) 合作，这是一个为期 4 周的实践暑期学院，为 4-8 年级教师提供研究经验； (2) 通过麻省理工学院的埃杰顿中心外展计划开发 3 小时的科学体验，旨在为高中生提供科学实践经验； (3) 每季度在 UCLA 创建一个新的课程模块，并让 3-4 名 UCLA 本科生参与研究；这些本科生将通过 UCLA CARE（卓越学术与研究中心）和 UC LEADS（通过高级学位培养卓越领导力）项目从代表性不足的群体中选拔； （4）细胞生物学和微流控领域研究生和博士后的培养。这些计划将共同促进多个教育层面的外展和科学教育。按照所有三个 PI 的传统，在技术和通俗文献中广泛传播成果将补充这一推广计划。