Dynamics of the Traumatic Brain Injury Degradome.

描述（由申请人提供）：创伤性脑损伤（TBI）是一种复杂的神经系统疾病，是我们社会的主要负担。TBI病因学需要许多学科，包括定量物理科学，如NIH路线图所述。该奖项促进定量科学家融入TBI的重点研究，这是该提案的精神。作为一名分析化学家，具有定量质谱分析的专业知识，我为NASA航天飞机发射的未来安全开发了地面支持仪器。最近，我开始在蛋白质研究中使用定量质谱法，这是当我发现我的专业知识将对神经创伤研究产生重大影响时。该奖项将确保我的直接职业目标，通过以下方式过渡到健康科学：1）提供必要的资金和保护时间，通过课程工作，研讨会和讲习班接受神经科学和分子细胞生物学的培训; 2）提供书面的机构承诺，以支持上述职业发展和晋升为医学院的全职终身教职人员;和3）在著名的McKnight Brain Institute内提供结构化的指导研究环境，以发展TBI研究中的生物研究技能，在医学科学中展示和发表，并作为主要研究者为未来的拨款提交生成初步数据。完成这份提案将使我能够实现我的长期目标，成为一名全职独立调查员，将定量和健康科学结合起来解决神经系统疾病。该研究将导师在TBI和蛋白水解方面的专业知识与我的定量化学背景相结合，是第一个大规模的TBI后降解组学研究。本研究将通过以下四个具体目标进行：1）开发新的标记化学方法来鉴定TBI相关蛋白酶的体外脑底物; 2）确定TBI后TBI相关蛋白酶激活的体内空间和时间动力学;第三章通过在蛋白酶活化的时间和空间分布内定量目标1中鉴定的底物来表征TBI后的体内底物降解，目标2;以及4）汇集并公开分发TBI降解区的概况（地图和时间轴）。这项研究将提供一个详细的表征分子事件，加剧脑损伤后头部创伤。了解这些事件将促进新的诊断和治疗方法的发展，以减少脑创伤对社会的负担。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a complex neurological disease and a major burden in our society. TBI etiology requires many disciplines, including quantitative physical sciences, working together as outlined in the NIH roadmap. This Award fosters integration of quantitative scientists into focused study of TBI, which is the spirit of this proposal. As an analytical chemist, with expertise in quantitative mass spectrometry, I developed ground support instrumentation for the future safety of NASA Space Shuttle launches. More recently, I began to use quantitative mass spectrometry in protein studies, which is when I discovered the significant impact that my expertise would have on neurotrauma research. This Award will ensure my immediate career goal to transition into the health sciences via the following: 1) provide the funding and protected time necessary to receive training in neuroscience and molecular cell biology through course work, seminars and workshops; 2) provide written institutional commitments to support the above career development and a promotion to full-time tenure-track faculty in the College of Medicine; and 3) provide a structured mentored research environment within the renowned McKnight Brain Institute to develop biological research skills in the study of TBI, present and publish within the medical sciences, and generate preliminary data for future grant submissions as a primary investigator. Completing this proposal will position me to achieve my long-term goal of becoming a full-faculty independent investigator, combining quantitative and health science in the resolution of neurological disorders. The research proposed, combines the mentors' expertise in TBI and proteolysis in synergy with my quantitative chemistry background, and is the first large scale post-TBI degradomic study. This research will be conducted through the following four Specific Aims: 1) develop novel tagging chemistry methodology to identify in vitro brain substrates of TBI-relevant proteases; 2) define in vivo spatial and temporal dynamics of TBI-relevant protease activation after TBI; 3) characterize in vivo substrate degradation after TBI by quantifying substrates identified in Aim 1 within temporal and spatial profiles of protease activation revealed in Aim 2; and 4) assemble and publicly distribute a profile (map and timeline) of the TBI degradome. This research will provide a detailed characterization of molecular events that exacerbate brain damage after head trauma. An understanding of these events will foster development of novel diagnostics and therapeutics to reduce the burden of brain trauma on society.