With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. David Baker for a project to engage the Foldit community in a collaborative citizen science effort to address the ongoing Ebola outbreak in West Africa. Foldit is a game-based protein design platform that engages gamers drawn from the community at large. This project involves collaboration among the Foldit game-based scientific community, The University of Washington's Institute for Protein Design (IPD), and The University of Washington's Center for Game Science, to improve and tailor the Foldit design platform in order to arrive at proteins that bind and neutralize the Ebola glycoprotein. The project will collectively harness the expertise of computer scientists and protein design experts in collaboration with the constantly growing citizen scientist community to arrive at totally novel functional proteins in an efficient and rapid manner. The proposed research will deliver critical insight into the structure and binding modes of potential anti-Ebola therapeutics; development of these anti-Ebola binders will be extremely valuable both for academic and industrial communities. The work will also significantly expand and broaden the citizen scientist community focused on discovering anti-viral therapeutics for Ebola. In addition to advancing development of anti-Ebola therapeutics, this project will continue to educate the public at large about Ebola, its epidemiology and current research efforts underway to combat this virus.
This project sets out to improve the Foldit game-based scientific environment in the direction of rapid and direct collaboration among the Foldit community, The University of Washington's Institute for Protein Design (IPD) and The University of Washington's Center for Game Science. The project will use Foldit puzzle challenges to facilitate the design of novel anti-viral proteins that bind to the surface glycoproteins of Ebolaviruses, and will experimentally test these binders for in vitro efficacy in collaborator laboratories. The approaches involve (a) customizing the Foldit protein design platform for Ebola studies, (b) engaging the Foldit citizen scientist community with anti-Ebola directed protein design challenges, (c) refining the anti-Ebola Foldit player designs, (d) preparing synthetic genes and manufacturing anti-Ebola proteins with the designed proteins and (e) testing the optimized anti-Ebola proteins prepared, in cell-based studies and animal models. The project will enlist the knowledge of a broad cadre of experts in the design of novel protein binders targeting Ebola and will utilize the Foldit platform to continually educate the public about project progress and more broadly about the virus itself with regular updates and feedback on the work.