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.