{"193701":{"#nid":"193701","#data":{"type":"event","title":"Paul C\u00e1rdenas Lizana - Ph.D. Proposal Presentation","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EAdvisor\u003C\/strong\u003E:\u003Cbr \/\u003ECheng Zhu, Ph.D. (BME, GATech)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECommittee\u003C\/strong\u003E:\u003Cbr \/\u003EAndr\u00e9s Garc\u00eda, Ph.D. (ME, GATech)\u003Cbr \/\u003ESteve Harvey, Ph.D. (BIO, GATech)\u003Cbr \/\u003EJizhong Lou, Ph.D. (Biophysics, Chinese Academy Of Sciences) \u003Cbr \/\u003ERodger McEver, Ph.D. (Molecular Biology - Oklahoma Medical Research Foundation)\u003Cbr \/\u003E\u003Cbr \/\u003EI propose to use Molecular Dynamics (MD) simulations to study the stability, the conformational changes, and the ligand dissociation of membrane receptors under mechanical forces. Two receptors of the immune system\u2013 the Selectins and the Integrins and one blood glycoprotein involved in homeostasis\u2013 von Willebrand factor (vWF) will be studied. Selectin-ligand interactions mediate the first step of a multistep adhesion and signaling cascade that recruits leukocytes to inflamed endothelium at sites of infection and injury. Malfunction of these interactions can result in a number of inflammatory and thrombotic disorders. Integrins are a family of heterodimeric molecules that mediate cell adhesion and signaling. Ligand binding of \u03b22 Integrins mediates the subsequent steps of the leukocyte recruitment cascade, which converts rolling adhesion to stable adhesion of leukocytes to endothelium. Both Selectins and Integrins are functionally important to immune system. The immune system protects the body from pathogens such as bacteria and viruses and diseased tissues such as cancer. Insufficient and over-reactive immune responses lead to various diseases. The vWF is a multimeric protein circulating in the plasma that functions as the main clotting factor to induce platelet aggregation and thrombus formation in blood vessels subjected to high haemodynamic shears.\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;In this proposal, the structural mechanisms of conformational changes, and the structural mechanisms of mechanical priming and force-history dependence will be investigated in L- and P-Selectin-ligand interactions. The activation pathway of \u03b1v \u03b23 and \u03b1x \u03b22 Integrin, and their conformational changes in the inside-out signaling when the trans-membrane cytoplasmic tails are unclasped, will be unraveled. Mechanical regulation between platelet GPIb\u03b1 and vWF, and the importance of mutant residues in their initial binding will be examined.\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;The groundwork of this proposal is MD simulation combined with rigorous experimental data produced in the Zhu lab. This kind of study is novel and provides a unique means for elucidating the mechanical regulation of bio-molecular interactions at the atomic resolution.\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003E\u0022Structural Basis of Mechanically Regulated Selectin, Integrin, and von Willebrand Factor Functions\u0022\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Structural Basis of Mechanically Regulated Selectin, Integrin, and von Willebrand Factor Functions"}],"uid":"27547","created_gmt":"2013-02-20 10:42:01","changed_gmt":"2016-10-08 02:02:37","author":"Chris Ruffin","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2013-02-28T08:00:00-05:00","event_time_end":"2013-02-28T10:00:00-05:00","event_time_end_last":"2013-02-28T10:00:00-05:00","gmt_time_start":"2013-02-28 13:00:00","gmt_time_end":"2013-02-28 15:00:00","gmt_time_end_last":"2013-02-28 15:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"65448","name":"Bioengineering Graduate Program"}],"categories":[],"keywords":[{"id":"569","name":"bioengineering"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:chris.ruffin@ibb.gatech.edu\u0022\u003EMr. Chris Ruffin\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}