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: 1121692
• 负责人: Jeffrey Riffell
• 金额: $ 41万
• 依托单位: University of Washington
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121692&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.

尽管进行了一世纪的深入研究，但受精是最知名的基本生物学过程之一。通过流体传播提示，配子之间的化学信号传导发生在不同的分类单元中，具有高度不同的生殖策略，被认为在生殖中起着基本作用。尽管如此，尚不清楚配子之间的化学通信如何在自然条件下发生。化学提示有效性及其对雄性配子运动的影响的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或交替抑制粘附和结合来促进细胞相互作用，但对于流动对雄性配子的运动性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施肥中的作用的能力有限。在微观尺度上准确控制流体运动和化学提示非常困难。在这个项目中，最先进的微流体方法将使对配子自然居住的微环境进行前所未有的控制。这项研究将采用一种全面的方法，并采用微流体来确定物理和化学在配子相互作用中扮演的角色。因此，在PIS Jeff Riffell（U. Washington），Roman Stocker（MIT）和Richard Zimmer（UCLA）的指导下进行的拟议研究围绕两个主要目的进行了构建：（i）确定化学线索对男配子运动的影响以及对男配子运动的影响； （ii）确定流体运动对男配子运动性及其对化学提示的反应的影响。三个PI之间的专业知识的协同和互补性将使男配子游泳的生物力学和生殖细胞之间化学通信的生物力学具有深入的特征。这项研究的全面和跨学科方法将对科学和社会产生广泛而多样的影响。对雄性配子趋化性的更好理解将是由于使用微流体技术而产生的，并提供有关生殖和保护生物学的新知识。同时，这项研究促进的进步在控制流体流量和微观的化学线索方面将为生物学领域提供广泛的方法论框架。这项研究中物理，生物学和化学的亲密结合将为高中，本科和研究生级的学生提供充足的培训机会，强调科学领域的代表性不足，通过（1）与华盛顿大学的暑期生命科学研究所（SILS）合作，为华盛顿大学提供了4周的4周暑期研究所，为4-8名教师提供了4-至8年级的研究经验； （2）通过MIT的Edgerton Center Outreach计划提供3小时的科学经验，该计划旨在高中生促进科学实践经验； （3）在UCLA创建一个新的课程模块，并在每个季度参与研究中的3-4个UCLA大学生；这些本科生将通过UCLA护理（卓越学术和研究中心）和UC Leads（通过高级学位的领导力）计划从代表性不足的群体中汲取灵感； （4）对研究生的培训，并在细胞生物学和微流体学领域进行培训。这些计划将在多个教育水平上促进外展和科学教育。按照所有三个PI的传统，对技术和流行文学的结果的广泛传播将补充这一外展计划。