{"345681":{"#nid":"345681","#data":{"type":"event","title":"Young Innovators in Biomedical Engineering","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003E\u0022Single-cell Secretion Analysis Reveals Paracrine Strategies for Coordinating Innate Immune Responses in Cell Populations\u0022\u003C\/strong\u003E\u003Cbr \/\u003E \u003Cbr \/\u003E \u003Cstrong\u003EKathryn Miller-Jensen, PhD\u003C\/strong\u003E\u003Cstrong\u003E\u003Cbr \/\u003E \u003C\/strong\u003E\u003Cstrong\u003EAssistant Professor, Department of Biomedical Engineering\u003C\/strong\u003E\u003Cstrong\u003E\u003Cbr \/\u003E \u003C\/strong\u003E\u003Cstrong\u003EYale University\u003C\/strong\u003E\u003Cbr \/\u003E \u0026nbsp; \u003Cbr \/\u003E Seminar will be made available via videoconference in the Health Sciences Research Building, room E182 and Technology Enterprise Park, room 104.\u003Cbr \/\u003E \u003Cbr \/\u003E Cell responses are mediated by intermediate signals that are secreted and sensed by the same cells and are subject to significant cell-to-cell heterogeneity. The propagation of these intermediate signals by extracellular signaling impacts the collective cell-population response, but the contribution of autocrine versus paracrine signaling is difficult to analyze. To address this, we have combined multiplexed, microwell single-cell secretion measurements with cell-population data to uncover the role of paracrine signaling in shaping the inflammatory response in human macrophages following toll-like receptor 4 (TLR4) stimulation with lipopolysaccharide (LPS). We demonstrate that loss of paracrine signaling upon single-cell isolation in microwells significantly alters secretion of some LPS-stimulated cytokines. Gaussian graphical models of these single-cell \u201cperturbation\u201d data sets specifically uncover regulatory connections between cytokines in the LPS-stimulated network. Tumor necrosis factor-\u03b1 (TNF), the most highly connected cytokine in the network, exhibits highly heterogeneous secretion, such that a small fraction of cells appears to drive total TNF output in the cell population. Using a mechanistic ODE model fit to our single-cell data, we demonstrate that this small fraction of high TNF secretors combined with positive feedback amplifies the pro-inflammatory IL-6 response in cell populations. Overall, our results reveal a novel role for paracrine cell-to-cell communication in coordinating a rapid and reliable innate immune response in spite of underlying cell-to-cell heterogeneity.\u0026nbsp; \u003Cbr \/\u003E \u003Cbr \/\u003E \u003Ca href=\u0022https:\/\/www.bme.gatech.edu\/bme\/faculty\/Melissa-Kemp\u0022 target=\u0022_blank\u0022\u003EMelissa Kemp, PhD\u003C\/a\u003E - faculty host\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EYoung Innovators in Biomedical Engineering - \u0022Single-cell Secretion Analysis Reveals Paracrine Strategies for Coordinating Innate Immune Responses in Cell Populations\u0022 - Kathryn Miller-Jensen, PhD - Yale University\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"\u0022Single-cell Secretion Analysis Reveals Paracrine Strategies for Coordinating Innate Immune Responses in Cell Populations\u0022 - Kathryn Miller-Jensen, PhD - Yale University"}],"uid":"27159","created_gmt":"2014-11-13 15:24:59","changed_gmt":"2017-04-13 21:21:07","author":"Vickie Okrzesik","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2014-11-25T10:00:00-05:00","event_time_end":"2014-11-25T11:00:00-05:00","event_time_end_last":"2014-11-25T11:00:00-05:00","gmt_time_start":"2014-11-25 15:00:00","gmt_time_end":"2014-11-25 16:00:00","gmt_time_end_last":"2014-11-25 16:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"related_links":[{"url":"http:\/\/seas.yale.edu\/faculty-research\/faculty-directory\/kathryn-miller-jensen","title":"Miller-Jensen profile"}],"groups":[{"id":"1254","name":"Wallace H. Coulter Dept. of Biomedical Engineering"}],"categories":[],"keywords":[{"id":"1613","name":"Biomedical Engieering"},{"id":"12016","name":"Young Innovators"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[{"id":"78751","name":"Undergraduate students"},{"id":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:melissa.kemp@bme.gatech.edu\u0022\u003EMelissa Kemp, PhD\u003C\/a\u003E - faculty host\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}