{"681409":{"#nid":"681409","#data":{"type":"event","title":"Immunoengineering Trainee Seminar","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EFeatured Speakers\u003C\/strong\u003E\u003Cbr\u003E\u003Cbr\u003E\u0022\u003Cem\u003E\u003Cstrong\u003EThe Co-agonist Effect of Wild-type p53 on a Clinically Relevant Tumor Antigen Reactive TCR, a Biophysical and Mechanistic Study\u0022\u003C\/strong\u003E\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EValencia Watson, Ph.D. Student, Cheng Zhu, Advisor - Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech \/ Emory University\u003C\/strong\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003EAbstract\u003C\/strong\u003E\u003Cbr\u003EWhen sampling a cell, cytotoxic T cells make direct physical contact with the target cell to determine immunogenic protein expression. T cells can recognize whether a cell exhibits antigenic protein expression through bond formation between T cell receptors (TCRs) and peptide loaded major histocompatibility complexes (pMHCs) expressed on the surface of the target cell. In the absence of antigenic infection, pMHCs exclusively express endogenous\/self-epitopes. Non-stimulatory self-pMHCs do not induce a T cell response alone, however, when antigenic infection occurs, both antigenic and endogenous pMHCs expressed on the surface of the target cell are sampled by TCRs to produce a response. Studies have shown that self-pMHC enhances CD8+ T cell responses to antigenic pMHC. This is referred to as the co-agonist effect. The physiological significance and molecular mechanism of this phenomenon are not clearly understood, especially at the bond level. TCRs require force to sample pMHC, thereby leading to an internalized signaling cascade, and ultimately the carrying out of effector functions. CD8 is a co-receptor that works in tandem with the TCR to potentiate the response from \u2018outside\u2019 receptor binding to \u2018inside\u2019 intracellular response. We are interested in studying TCR mechanosensing in bond formation, and how endogenous TCR pulling is influenced by the co-agonist effect. Here, we have identified a previously unknown co-agonist of a clinically relevant, tumor antigen responsive TCR. We demonstrate the co-agonist effect using wild type p53, the \u2018guardian of the genome\u2019, and a single point hot spot p53 mutant, R175H, a gain of function tumor antigen. Using single cell analysis, we explore how the TCR mechanosensing is impacted by the co-agonist effect and dive into the molecular mechanism of the CD8 co-receptor and its role in co-agonism at the bond level.\u003C\/p\u003E\u003Cdiv\u003E\u003Cp\u003E\u003Cbr\u003E\u003Cem\u003E\u003Cstrong\u003E\u0022High Cell Throughput, Programmable Fixation Reveals the RNA and Protein Co-regulation with Spatially Resolved NF\u03baB Pseudo-signaling\u0022\u003C\/strong\u003E\u003C\/em\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003ENicholas Zhang, Ph.D. Student, Ahmet Coskun, Advisor - Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech \/ Emory University\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EAbstract\u003C\/strong\u003E\u003Cbr\u003ERNA translation to protein is paramount to creating life, yet RNA and protein correlations vary widely across tissues, cells, and species. To investigate these perplexing results, we utilize a time-series fixation method that combines static stimulation and a programmable formaldehyde perfusion to map pseudo-Signaling with Omics signatures (pSigOmics) of single-cell data from hundreds of thousands of cells. Using the widely studied nuclear factor kappa B (NF\u03baB) mammalian signaling pathway in mouse fibroblasts, we discovered a novel asynchronous pseudotime regulation (APR) between RNA and protein levels in the quintessential NF\u03baB p65 protein using single molecule spatial imaging. Prototypical NF\u03baB dynamics are successfully confirmed by the rise and fall of NF\u03baB response as well as A20 negative inhibitor activity by 90 min. The observed p65 translational APR is evident in both statically sampled timepoints and dynamic response gradients from programmable formaldehyde fixation, which successfully creates continuous response measurements. Finally, we implement a graph neural network model capable of predicting APR cell subpopulations from GAPDH RNA spatial expression, which is strongly correlated with p65 RNA signatures. Successful decision tree classifiers on Potential of Heat-diffusion for Affinity-based Trajectory Embedding embeddings of our data, which illustrate partitions of APR cell subpopulations in latent space, further confirm the APR patterns. Together, our data suggest an RNA-protein regulatory framework in which translation adapts to signaling events and illuminates how immune signaling is timed across various cell subpopulations.\u003C\/p\u003E\u003C\/div\u003E\u003Cp\u003E\u003Cem\u003EThe Immunoengineering Training Seminar Series is supported by the\u0026nbsp;\u003C\/em\u003E\u003Ca href=\u0022https:\/\/immunoengineering.gatech.edu\/\u0022\u003E\u003Cem\u003E\u003Cstrong\u003ECenter for Immunoengineering at Georgia Tech\u003C\/strong\u003E\u003C\/em\u003E\u003C\/a\u003E\u003Cem\u003E.\u0026nbsp;\u003C\/em\u003E\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EValencia Watson (Cheng Zhu Lab) and Nicholas Zhang (Ahmet Coskun Lab) presenting\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Valencia Watson (Cheng Zhu Lab) and Nicholas Zhang (Ahmet Coskun Lab) presenting"}],"uid":"27195","created_gmt":"2025-03-27 14:01:11","changed_gmt":"2025-03-27 17:58:56","author":"Colly Mitchell","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2025-04-04T09:30:00-04:00","event_time_end":"2025-04-04T10:30:00-04:00","event_time_end_last":"2025-04-04T10:30:00-04:00","gmt_time_start":"2025-04-04 13:30:00","gmt_time_end":"2025-04-04 14:30:00","gmt_time_end_last":"2025-04-04 14:30:00","rrule":null,"timezone":"America\/New_York"},"location":"Petit Biotech Building (IBB), Suddath Seminar Room 1128, 315 Ferst Drive","extras":[],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1254","name":"Wallace H. Coulter Dept. of Biomedical Engineering"}],"categories":[],"keywords":[{"id":"187423","name":"go-bio"},{"id":"189814","name":"go-researchevents"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"177814","name":"Postdoc"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:dbalasub3@gatech.edu\u0022\u003EDeepali Balasubramani\u003C\/a\u003E - series coordinator\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}