Interaction between innate and Th2 lymphocytes in helminth immunity

描述(由申请人提供)：这是加州大学旧金山分校医学博士Jesse Nussbaum的一份K08学位的初步申请。努斯鲍姆博士已经完成了传染病方面的奖学金培训，现在正在寻求资金和受保护的时间进行培训，以发展宿主与寄生虫相互作用的独立内科科学家职业生涯。这位候选人在基础和临床研究方面表现出色，他在培训的每个阶段发表的工作都证明了这一点。他最近加入了理查德·洛克斯利博士的实验室，获得了使用模型生物研究宿主免疫领域的专业知识。这项提议有两个培训目标：(1)职业发展计划说明努斯鲍姆博士为实现科学独立而需要掌握的科学领域(如免疫学、寄生虫学、显微镜)和专业能力(如陈述、撰写补助金)。该计划详细说明了课程作业、研讨会和指导的基准。(2)努斯鲍姆博士的研究策略解决了一个具有临床和科学意义的重要课题。了解启动和维持对蠕虫的免疫反应的保守信号将回答有关共同进化的宿主和病原体相互作用的关键问题，并使改善发展中国家生活的疗法成为可能。这一研究计划既具有创新性，又具有可实现性。它使用成熟的模型和现有的小鼠品系来定义T辅助细胞和新发现的固有淋巴细胞之间的新的相互作用。候选人的具体目标是定义(1)这些细胞-细胞相互作用的动态特性，(2)这些细胞对记忆免疫反应的相对贡献，以及(3)激素信号在淋巴细胞激活中的作用。这些目标建立在努斯鲍姆博士之前工作的基础上，但也融入了需要进一步培训的新技术。努斯鲍姆博士组建了一个指导委员会，成员包括主要导师、医学和微生物学及免疫学教授、传染病和免疫学内科科学家专家理查德·洛克斯利博士；免疫系统高级成像专家马修·克鲁梅尔博士；宿主-寄生虫生物学和药物发现专家詹姆斯·麦克罗博士；以及T细胞开发专家和加州大学旧金山分校医学科学家培训项目主任马克·安德森博士。该委员会的结构旨在提供互补的科学和职业观点，其成员是密切的合作者。Nussbaum博士得到了传染病系的全力支持，他将在那里担任助理教授，这一职位不取决于获得这一奖项。加州大学旧金山分校的机构环境提供了资源充足的设施和培训早期内科科学家的良好记录。医学系和免疫学和微生物学系将通过获得不同的教员合作和用于研究活动的受保护时间(至少75%)来帮助候选人。这项提议为Nussbaum博士的进一步职业发展奠定了基础，确保了培训和对科学的原创贡献，使他能够竞争他的独立研究计划的资金。

DESCRIPTION (provided by applicant): This is an initial application for a K08 for Jesse Nussbaum, MD at the University of California, San Francisco. Dr. Nussbaum has completed fellowship training in Infectious Diseases and now seeks funding and protected time for training to develop an independent physician scientist career in host-parasite interactions. The candidate has excelled in basic and clinical research, as evidenced by publication of his work at each stage of his training. He most recently joined the laboratory of Dr. Richard Locksley to gain expertise in the use of model organisms to study the field of host immunity. This proposal has two training goals: (1) The career development plan describes the scientific fields (e.g. immunology, parasitology, microscopy) and professional competencies (e.g. presentation, grant-writing) that Dr. Nussbaum will need to master in order to achieve scientific independence. The plan details benchmarks for coursework, seminars, and mentoring. (2) Dr. Nussbaum's research strategy addresses a clinically and scientifically important subject. Understanding the conserved signals that initiate and maintain immune responses to helminths will answer crucial questions about co-evolved host-pathogen interactions and enable therapies that improve life in the developing world. This research plan is both innovative and achievable. It uses well-established models and existing mouse strains to define novel interactions between T helper cells and newly discovered innate lymphocytes. The candidate's specific aims are to define (1) the dynamic properties of these cell-cell interactions, (2) the relative contribution of these cell to memory immune responses, and (3) the role of hormonal signals in lymphocyte activation. These aims build on Dr. Nussbaum's previous work but also incorporate new techniques that require further training. Dr. Nussbaum has assembled a mentoring committee, comprised of primary mentor, Dr. Richard Locksley, Professor of Medicine and Microbiology and Immunology and physician-scientist expert in infectious diseases and immunology; Dr. Matthew Krummel, expert in advanced imaging of the immune system; Dr. James McKerrow, expert in host-parasite biology and drug discovery; and Dr. Mark Anderson, expert in T cell development and Director of the UCSF Medical Scientist Training Program. The committee is structured to provide complementary scientific and career perspectives, and its members are close collaborators. Dr. Nussbaum has the full support of the Division of Infectious Diseases where he will be an Assistant Professor, a position that is not contingent upon receiving this award. UCSF's institutional environment provides well-resourced facilities and a strong track record of training early-stage physician scientists. The Department of Medicine and Department of Immunology and Microbiology will assist the candidate through access to diverse faculty collaborations and protected time (at least 75%) devoted to his research activities. This proposal forms a basis for Dr. Nussbaum's further career development, ensuring training and original contributions to science that will allow him to compete for funding of his independent research program.