CAREER: Reactivity-Driven Metabolic Signaling: A Feature not a Flaw in Metabolic Regulation

职业：反应驱动的代谢信号：代谢调节中的一个特征而不是一个缺陷

• 批准号: 1945442
• 负责人: Raymond Moellering
• 金额: $ 73万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1945442&HistoricalAwards=false
• 关键词: CAREER; Reactivity; Driven; Metabolic; Signaling

Key to healthy cell function is proper control over metabolism - chemical reaction pathways that provide energy and produce molecules for making complex biological structures and send messages to various parts of the cell. While research efforts have defined many of the most basic chemical reaction pathways in cells, the changing connections between these pathways under normal and abnormal metabolic conditions remain largely unknown. Dr. Raymond Moellering develops new chemical tools and techniques to understand how glucose (sugar) metabolism - the dominant energy pathway in life - communicates with other pathways that sense and control the response of cells that are experiencing stress. In parallel, Dr. Moellering integrates this research with new coursework, on-campus research opportunities for local high school students, and the creation of an educational outreach program in local high schools. Collectively, these programs aim to provide students with hands-on research experiences and encourage them to pursue career paths in science, technology, engineering, and math fields. With this award, the Chemistry of Life Processes Program is funding Dr. Raymond Moellering at the University of Chicago to develop an integrated suite of chemical probes, proteomic methods, and cellular model systems to discover and quantify the role of a prototypical intrinsic reactive metabolite, methylglyoxal. Methylglyoxal regulates cellular homeostasis and complex phenotypes in cells and whole organisms. Dr. Moellering uses these methods and cross-species proteomic and metabolomic datasets in identifying novel protein targets involved in the response to reactive glycolytic metabolites. He studies the two candidate proteins already identified. Research objectives are integrated with three educational goals that develop new coursework that brings together physical science pedagogy and student exposure to diverse career options for science, technology, engineering and math (STEM). The team provides educational research opportunities for local high school students on-campus at the University of Chicago and in local high schools. The coursework, summer research areas, and basic science lectures consider the role of chemical probes and techniques in understanding basic biology and wellness in society.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

健康细胞功能的关键是对新陈代谢的适当控制 - 化学反应途径提供能量并产生分子以形成复杂的生物结构并向细胞的各个部分发送信息。尽管研究工作已经定义了细胞中许多最基本的化学反应途径，但在正常和异常代谢条件下这些途径之间的变化联系在很大程度上仍然未知。 Raymond Moellering 博士开发了新的化学工具和技术，以了解葡萄糖（糖）代谢（生命中的主要能量途径）如何与感知和控制正在经历压力的细胞的反应的其他途径进行通信。与此同时，莫勒林博士将这项研究与新课程、为当地高中生提供的校园研究机会以及在当地高中创建的教育推广计划相结合。总的来说，这些项目旨在为学生提供实践研究经验，并鼓励他们在科学、技术、工程和数学领域追求职业道路。 凭借该奖项，生命过程化学计划正在资助芝加哥大学的 Raymond Moellering 博士开发一套化学探针、蛋白质组学方法和细胞模型系统的集成套件，以发现和量化原型内在反应性代谢物甲基乙二醛的作用。 甲基乙二醛调节细胞和整个生物体的细胞稳态和复杂表型。 Moellering 博士使用这些方法以及跨物种蛋白质组和代谢组数据集来识别参与反应性糖酵解代谢物反应的新蛋白质靶标。 他研究了已经确定的两种候选蛋白质。研究目标与三个教育目标相结合，开发新的课程，将物理科学教学法和学生接触科学、技术、工程和数学 (STEM) 的多样化职业选择结合起来。 该团队为芝加哥大学校园和当地高中的当地高中生提供教育研究机会。课程作业、夏季研究领域和基础科学讲座考虑了化学探针和技术在理解基础生物学和社会健康方面的作用。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。