Transcriptional regulation of immunological memory in innate and adaptive lymphocytes

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PROJECT SUMMARY The candidate, Dr. Colleen Lau seeks to achieve an academic career as an independent research investigator at an institution where she can foster academic growth and immunology research that advances treatment or prevention of human disease. She aims to do so through a union of laboratory experimentation and bioinformatics methods, as reflected in her current proposal. Her project aims to understand the underlying mechanisms that drive proper formation of immune memory by studying it in two cytolytic lymphocytes in the context of viral infection, using mouse cytomegalovirus (CMV) as a model. By studying the infection in mice, work performed previously in the lab has demonstrated that natural killer (NK) cells, cytolytic lymphocytes traditionally classified as innate cells, are capable of exhibiting attributes of adaptive immune memory. As a result, her previous work used these CMV- specific NK cells and the more classic adaptive CD8+ T cell to further illustrate that these two lymphocytes share a common transcriptional and epigenetic memory signature. Building from this signature, she will hone in on two candidate transcription factors, ZEB2 and JunB, to test their requirement for optimal effector function, memory formation, memory maintenance and recall in both cell types, using genetic mouse models that temporally delete the gene. Using a combination of high-throughput sequencing technologies, she will generate global transcriptomic, epigenomic, and transcription factor occupancy profiles in order to elucidate any common mechanisms between memory NK and CD8+ T cells. This proposal improves our understanding of antiviral processes and immune memory in order to ultimately harness it for vaccine therapy and disease intervention. Throughout the transition and award period, the candidate will focus on advancing her technical and computational skills for generating and analyzing large and complex datasets, improving and exercising her mentoring skills, broadening her scientific background through regular attendance of scientific seminars and conferences, and developing her grant writing skills. She aspires to acquire a tenure-track faculty position, and, with the informal guidance of her previous mentors, strives to carry out her long-term research program of studying immunological memory.