PROJECT SUMMARY The microbiome has become an essential element of biomedical science as recent research has uncovered the connection between human microbiome composition, diet, environment, and the incidence of a wide variety of the most serious and life-threatening human health conditions, such as cancer, cardiovascular disease, autoimmune disorders, musculoskeletal diseases, and antibiotic resistance. Despite knowledge of these critical connections, research on effective microbiome-based treatments for health problems is still in its infancy and there is vast untapped potential for groundbreaking discoveries. Teaching K-12 students about the biomedical science behind the microbiome, diet, and environment that are directly relevant to their everyday lives therefore has the potential to increase their interest in biomedical science, develop quantitative and computational problem-solving skills essential for biomedical research, and empower them to play a role in disseminating biomedical science via public health advocacy. Exposure to such education is especially critical at the high school level when students are contemplating future career paths. To meet this critical need, SIFT, Colby College, and Jackson Labs propose Gut Grieff, a low-cost, web-based digital game that teaches high school students to think about genomics quantitatively, computationally, and predictively through active engagement, strategic problem-solving, and customized feedback emulating how high school biology instructors teach their students. Non-violent gameplay and educational content relevant to students' everyday lives present an inclusive environment designed to appeal to students regardless of their experiences playing games. Phase I of this Small Business Innovation Research (SBIR) project will produce a low-fidelity prototype with tasks demonstrating specific game mechanics designed to teach core genomics concepts: healthy microbiome composition; species interdependence, including the host; influence of biotic and abiotic factors; and strategies for maintaining healthy microbiome (Aim 1, Sub Aim 1 ). The Gut Grieff prototype will also include a cutting-edge artificial intelligence (Al) system that monitors player performance and appropriately modifies game content to improve learning outcomes (Aim 1, Sub Aim 2). Gut Grief!'s low-fidelity prototype will be evaluated in terms of usability (Aim 2) and its efficacy at teaching microbiome concepts, engaging the learner, and increasing students' interest in biomedical science (Aim 3). Gut Grieff will be the first scalable, game-based, and adaptive biomedical education tool targeting the microbiome and promoting transfer of in-game learning to traditional biology assessments. Gut Grieff will be a web-based game, allowing easy set up and scalability regardless of individual computers' capabilities. Making Gut Grieff commercially available to high schools, outreach organizations, and the general public has the potential to d...