CAREER: Dynamic and Intrinsic Profiling of Membrane Microdomain Composition, Function and Regulation

这项由生物技术、生化和生物质工程项目颁发的美国国家科学基金会职业奖，支持一项研究和教育项目，该项目专注于发现构成细胞膜微域的物种的功能，并通过专业发展促进女性在STEM学科中的进步。膜物种对于调节无数的细胞过程是必不可少的，对于使用这些物种作为传感器的生物分析测定和传感器的正常功能至关重要。然而，我们对蛋白质功能之间的联系以及蛋白质局部膜环境对其功能的影响的理解是缺乏的。在这项工作中，我们将采用一种新型的微流体装置，由图案组成，两相共存的膜来评估生物分子在不同膜相中的分配；识别触发分区变化的刺激物；量化分配是如何影响并可能调节蛋白质功能的。了解蛋白质功能如何依赖于局部膜组成对于理解膜生物学至关重要，了解膜环境如何影响药物-蛋白质相互作用对于评估减轻糖尿病、阿尔茨海默病和不孕症等疾病的治疗效果是必要的，在这些疾病中，细胞膜组成的变化与疾病的表现有关。因此，本研究的广泛影响正在填补膜蛋白质组学研究的技术空白，该研究将用于研究分配如何依赖于膜特性和外部刺激（化学，生物，环境），最终监测异质膜中物种之间的直接相互作用，并确定相互作用后蛋白质活性的变化。与研究计划相一致的是，将通过一个新的多层次专业发展计划，实施教育工作，指导研究生和博士后女性成为成功的领导者和教育家。该教育计划将通过同侪辅导、外联项目和职业网络研讨会来教授领导技能和教育能力。该教育计划的广泛影响正在填补STEM学科年轻女性专业人员的本科晋升计划和专业发展计划之间的空白；创建一种女性研究生教育模式，将工程技术教育与领导和管理技能相结合，培养全面发展、有技术能力的毕业生；并最终增加研究生毕业后选择高级技术职业的女性人数。

CBET 1149452/ DanielThis NSF CAREER award by the Biotechnology, Biochemical and Biomass Engineering program supports a research and education program focused on discovering the function of species that comprise cell membrane microdomains and promoting the advancement of women in STEM disciplines through professional development. Membrane species are essential for regulating myriad cellular processes and vital to proper function of bioanalytical assays and sensors that employ these species as transducer elements. Yet our understanding of the links between protein function and the impact of the local membrane environment of that protein on its function is lacking. In this work, we will employ a novel microfluidic device comprised of patterned, two-phase co-existent membranes to assess biomolecule partitioning into different membrane phases; identify the stimuli that trigger changes in partitioning; and quantify how partitioning impacts, and possibly regulates, protein function. Knowing how protein function depends on the local membrane composition is vital to understanding membrane biology and appreciating how the membrane environment impacts drug-protein interactions is necessary for assessing therapeutic efficacy in mitigating diseases such as Diabetes, Alzheimer's disease, and infertility, where changes in cell membrane composition are implicated in the disease manifestation. Thus the broader impacts of this research are filling a technological gap in membrane proteomic research that will be used to study how partitioning depends on membrane properties and external stimuli (chemical, biological, environmental) to ultimately monitor direct interactions between species in heterogeneous membranes and determine protein activity changes after interaction. Coincident to the research plan, educational efforts on coaching graduate and post doctoral women to become successful leaders and educators will be implemented through a new multi-layered professional development program. The education plan will build leadership skills and educational competency through peer mentoring, teaching leadership skills through outreach programs, and career networking workshops. The broader impacts of this education plan are filling the gap between undergraduate advancement programs and professional development programs for young female professionals in the STEM disciplines; creating a model for female graduate student education that combines technical education in engineering with leadership and management skills to yield well-rounded, technically competent graduates; and ultimately increasing the number of women choosing advanced technical careers after graduate school.