Investigating the role of the microbiota in enhancing memory T cell function during caloric restriction to promote melanoma control

项目摘要/摘要 研究：发现提高记忆T细胞质量的新因素和新机制有可能 影响癌症免疫疗法的发展。我最近发表的文章表明，卡路里限制(CR) 增强记忆T细胞控制黑色素瘤的功能，显著延长宿主存活时间。因此，CR可以 代表了一种可获得的营养干预，以调节免疫系统的功能，用于治疗 癌症。然而，涉及的分子决定因素和信号通路仍然不清楚，这对 发现，以便合理设计和实施以饮食为基础的治疗方法。根据初步数据 和其他人发表的工作，这项提议将调查微生物区系衍生的醋酸盐在促进 记忆性T细胞在CR期间发挥作用，以促进黑色素瘤的控制。这样的信息有可能造福于人类 通过改进旨在治疗癌症的策略来促进健康。 职业目标：我的首要职业目标是成为一家学术机构的独立调查员 我研究了CR可被用作营养干预以调节免疫系统的机制 癌症的治疗。此外，我认为教学和指导是成为一名 她是一名独立的调查员，因此立志成为一名鼓舞人心的教师和杰出的导师。 职业发展计划：为了成为一名成功的独立调查员，我需要开展各种研究， 专业技能和个人技能。这些将包括获得分子生物学和微生物学方面的专业知识。 技巧，以及促进合作和发展写作、指导、教学和交流的技能 和实验室管理。美国国立卫生研究院提供了一个优秀的学术环境，学员可以在其中完成这些任务 通过定期提交数据、接收知名科学家的反馈、促进合作和 参加课程以发展专业科学领域、个人发展和实验室管理方面的技能。 此外，除了我的导师和共同导师外，我还得到了几个独立调查人员的支持， 在将极大地促进完成这里提出的实验的领域中具有广泛的专业知识。因此，美国国家卫生研究院 是一个在K99阶段开发的理想环境，随着我成为一个成功的独立人士 调查员。 职业发展环境：我将在美国国立卫生研究院亚斯明·贝尔凯德博士的实验室里完成K99阶段的工作， 就现有的资源和设施而言，这提供了一个前所未有的环境。实验室里有 获得完成本申请中提出的实验所需的所有仪器和设施。 这些设施包括一个灵知生物动物设施和一个也提供生物信息学分析的测序设施。这个 我将得到最高标准的指导，将有许多合作机会。

Project summary/Abstract Research: To discover novel factors and mechanisms that enhance the quality of memory T cells has the potential to impact the development of cancer immunotherapies. My recent publication demonstrated that caloric restriction (CR) enhanced the function of memory T cells to control melanoma and significantly extend host survival. As such, CR could represent an accessible nutritional intervention to modulate the function of the immune system for the treatment of cancer. However, the molecular determinants and signalling pathways involved remain unclear, which are critical to uncover in order to rationally design and implement diet-based therapeutic approaches. Based on preliminary data and the published work of others, this proposal will investigate the role of microbiota-derived acetate in enhancing memory T cell function during CR to promote melanoma control. Such information has the potential to benefit human health by improving strategies aimed at treating cancer. Career Goals: My overarching career goal is to become an independent investigator at an academic institution where I study the mechanisms by which CR can be utilized as a nutritional intervention to modulate the immune system for the treatment cancer. Furthermore, I believe that teaching and mentoring are essential aspects of being an independent investigator and therefore aspire to become an inspirational teacher and an outstanding mentor. Career Development Plan: To become a successful independent investigator I will need to develop various research, professional and personal skills. These will include acquiring expertise in molecular biology and microbiology techniques, as well as fostering collaborations and developing skills in writing, mentoring, teaching, communicating and laboratory management. The NIH provides an outstanding academic environment in which trainees can fulfil these criteria by regularly presenting data, receiving feedback from prominent scientists, fostering collaborations and enrolling in courses to develop skills in specialist scientific areas, personal development and laboratory management. Furthermore, in addition to my mentor and co-mentor, I have support from several independent investigators with extensive expertise in areas that will greatly facilitate the completion of experiments proposed here. As such, the NIH is an ideal environment to develop during the K99 phase as I progress to become a successful independent investigator. Career Development Environment: I will perform the K99 phase in the laboratory of Dr. Yasmine Belkaid at the NIH, which provides an unprecedented environment in terms of the resources and facilities available. The laboratory has access to all of the instruments and facilities necessary to complete the experiments proposed in this application. These include a gnotobiotic animal facility and a sequencing facility that also provides bioinformatics analysis. The mentorship I will receive will be of the highest standard and there will be numerous opportunities to collaborate.