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

健康细胞功能的关键是适当控制新陈代谢--化学反应途径，它提供能量并产生分子，形成复杂的生物结构，并将信息发送到细胞的不同部分。虽然研究工作已经确定了细胞中许多最基本的化学反应途径，但这些途径在正常和异常代谢条件下变化的联系在很大程度上仍不清楚。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--生命中占主导地位的能量途径--如何与其他感知和控制正在经历压力的细胞的反应的途径进行沟通。同时，Moellering博士将这项研究与新的课程作业、为当地高中生提供的校园研究机会，以及在当地高中创建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。通过这一奖项，生命过程化学项目将资助芝加哥大学的Raymond Moellering博士开发一套集成的化学探针、蛋白质组学方法和细胞模型系统，以发现和量化典型的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的动态平衡以及细胞和整个生物体的复杂表型。Moellering博士使用这些方法和跨物种蛋白质组和代谢组学数据集来确定参与对活性糖酵解代谢物反应的新蛋白质靶点。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，这三个目标开发了新的课程，使物理科学教育学和学生接触到科学、技术、工程和数学(STEM)的不同职业选择。该团队为当地高中生在芝加哥大学校园内和当地高中提供教育研究机会。课程作业、暑期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优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.