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CAREER: Developing Thermal Gel Electrophoresis to Interrogate Higher Order Biological Structure

职业：开发热凝胶电泳来探究更高阶的生物结构

基本信息

批准号：
2046487
负责人：
Thomas Linz
金额：
$ 62.5万
依托单位：
Wayne State University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2046487&HistoricalAwards=false
关键词：
CAREER Developing Thermal Gel Electrophoresis

项目摘要

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, and partial co-funding from the Division of Chemical, Bioengineering, Environmental, and Transport Systems, Dr. Thomas Linz and his group at Wayne State University are developing innovative methods to measure biological molecules. Proteins must be “active” in biological samples and pharmaceutical formulations to carry out therapeutic functions. To improve the reproducibility of biological research studies and to screen the integrity of biopharmaceutical products, convenient low-cost methods are needed for determination of the amount of active protein in a sample, as opposed to the total amount of a target protein. The Linz Lab is addressing this need by developing technology to rapidly determine the fraction of protein molecules in their active states. A technique called thermal gel electrophoresis is being created that uses temperature-responsive materials to help distinguish active and inactive protein molecules. The methods created in the Linz Lab target rapid and inexpensive analysis of biological samples and biopharmaceuticals. The group is also developing associated outreach activities for elementary and middle school students to teach children how temperature impacts the properties of materials.Protein bioactivity is governed in part by folded conformations, multimeric complexes, and post-translational modifications. Screening for these higher order structures when validating biological samples or biopharmaceutical formulations can help determine and control the amount of active protein in the sample, rather than just total protein mass. The Linz Lab is developing methods in a microchip gel electrophoresis format to conveniently interrogate tertiary and quaternary structures and post-translational modifications. Thermal gel electrophoresis uses thermoresponsive polymers to integrate distinct analytical capabilities within a single microfluidic device including sample preparation, separation, and detection. These disparate functions are achieved by controlling temperature in the device with high spatial and temporal resolution to locally adjust gel viscosity for each analysis step. This approach minimizes complexity and cost of the microdevices and streamlines analyses to increase sample throughput. Ultimately, this rapid, inexpensive gel electrophoresis screening technique is expected to enhance the precision of biological research and enable the integrity of protein drug and vaccine formulations to be assessed in the field.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.

在化学系化学测量和成像项目的支持下，以及化学、生物工程、环境和运输系统系的部分共同资助下，托马斯林茨博士和他在韦恩州立大学的团队正在开发测量生物分子的创新方法。蛋白质必须在生物样品和药物制剂中具有“活性”，以实现治疗功能。为了提高生物学研究的再现性和筛选生物制药产品的完整性，需要方便的低成本方法来测定样品中活性蛋白的量，而不是靶蛋白的总量。林茨实验室正在通过开发技术来快速确定处于活性状态的蛋白质分子的分数来满足这一需求。一种称为热凝胶电泳的技术正在开发中，该技术使用温度响应材料来帮助区分活性和非活性蛋白质分子。林茨实验室创建的方法旨在快速、廉价地分析生物样品和生物药物。该小组还为中小学生开发了相关的外展活动，向孩子们教授温度如何影响材料的性质。蛋白质生物活性部分取决于折叠构象，多聚体复合物和翻译后修饰。在验证生物样品或生物药物制剂时筛选这些高阶结构可以帮助确定和控制样品中活性蛋白的量，而不仅仅是总蛋白质质量。林茨实验室正在开发微芯片凝胶电泳形式的方法，以方便地询问三级和四级结构和翻译后修饰。热凝胶电泳使用温敏聚合物将不同的分析能力集成在单个微流体装置内，包括样品制备、分离和检测。这些不同的功能是通过控制具有高空间和时间分辨率的设备中的温度来实现的，以局部调节每个分析步骤的凝胶粘度。这种方法最大限度地降低了微器件的复杂性和成本，并简化了分析，以增加样品的吞吐量。最终，这种快速、廉价的凝胶电泳筛选技术有望提高生物研究的精度，并使蛋白质药物和疫苗制剂的完整性得到现场评估。该奖项反映了NSF的法定使命，并被认为值得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来支持。