Transcriptional regulation of immunological memory in innate and adaptive lymphocytes

项目摘要 候选人，Colleen Lau博士寻求实现作为一个独立的研究学术生涯 研究人员在一个机构，在那里她可以促进学术发展和免疫学研究的进展， 治疗或预防人类疾病。她的目标是通过一个实验室实验联盟来实现这一目标 和生物信息学方法，正如她目前的提案所反映的那样。 她的项目旨在了解驱动免疫系统正确形成的潜在机制。 在病毒感染的情况下，通过在两个溶细胞淋巴细胞中研究记忆，使用小鼠 巨细胞病毒（CMV）作为模型。通过研究小鼠的感染，以前在实验室中进行的工作 证明自然杀伤（NK）细胞，传统上被归类为先天性细胞的溶细胞淋巴细胞， 能够表现出适应性免疫记忆的属性。因此，她以前的工作使用这些CMV- 特异性NK细胞和更经典的适应性CD 8 + T细胞进一步说明这两种淋巴细胞 有着共同的转录和表观遗传记忆特征从这个签名开始，她将磨练 两个候选转录因子，ZEB 2和JunB，以测试它们对最佳效应子功能的需求， 记忆形成，记忆维持和回忆在两种细胞类型，使用遗传小鼠模型， 暂时删除该基因。使用高通量测序技术的组合，她将 生成全局转录组学、表观基因组学和转录因子占用谱，以阐明 记忆NK和CD 8 + T细胞之间的任何共同机制。这一建议增进了我们对 抗病毒过程和免疫记忆的能力，以便最终将其用于疫苗治疗和疾病 干预 在整个过渡和奖励期间，候选人将专注于提高她的技术和 计算技能，用于生成和分析大型和复杂的数据集，提高和锻炼她 指导技能，通过定期参加科学研讨会扩大她的科学背景， 会议，并发展她的赠款写作技巧。她渴望获得终身教职， 在她以前的导师的非正式指导下，努力开展她的长期研究计划， 研究免疫记忆

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.