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

尽管经过了世纪的深入研究，受精仍然是人们最不了解的基本生物过程之一。配子之间的化学信号通过流体传播的线索发生在不同的类群具有高度不同的生殖策略，并被认为在生殖中发挥了重要作用。尽管如此，目前还不清楚配子之间的化学通讯是如何在自然条件下发生的。一个关键的决定因素的有效性的化学线索和他们的影响，男性配子的运动是周围的流体运动。流体运动可能会促进细胞相互作用，使配子在一起，或者可以抑制粘附和结合，但很少有人知道流动的运动性和趋化性的男性配子的影响。现有的方法在研究物理和化学在介导配子行为和受精中的作用方面能力有限。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前所未有地控制配子自然居住的微环境。这项研究将采取全面的方法，并应用微流体来确定物理和化学在配子相互作用中所起的作用。这项拟议中的研究将在PI的指导下进行。华盛顿），Roman Stocker（麻省理工学院）和Richard Zimmer（加州大学洛杉矶分校），因此围绕两个主要目标构建：（i）确定化学线索对雄性配子运动和受精成功的影响;（ii）建立流体运动对雄性配子运动及其对化学线索的反应的影响。三个PI之间的专业知识的协同作用和互补性将使深入的生物力学特征的雄性配子游泳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而多样的影响。微流控技术的应用将使人们更好地了解雄配子的趋化性，并为生殖和保护生物学提供新的知识。与此同时，这项研究在微观尺度上实现流体流动和化学线索控制方面的进展将为生物学的不同领域提供一个广泛的方法框架。在这项研究中，物理学、生物学和化学的紧密结合将为高中、本科和研究生阶段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，具体做法是：（1）与华盛顿大学生命科学暑期研究所（SILS）合作，这是一个为期四周的实践暑期研究所，为4 - 8年级的教师提供研究经验;（2）通过麻省理工学院的埃杰顿中心外展计划，为高中生提供3小时的科学体验，以促进科学实践经验;（3）在加州大学洛杉矶分校创建一个新的课程模块，每个季度有3 - 4名加州大学洛杉矶分校的本科生参与研究;这些本科生将通过UCLA CARE从代表性不足的群体中选拔（卓越学术和研究中心）和UC LEADS（通过高级学位的卓越领导）计划;（4）在细胞生物学和微流体研究生和博士后的培训。总之，这些计划将促进在多个教育层次的推广和科学教育。按照所有三个项目研究所的传统，在技术和大众文献中广泛传播研究结果，将补充这一推广计划。

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.