I-Corps: Enhanced Protein Discovery Tools for Proteomics Research

I-Corps项目的更广泛影响/商业潜力侧重于为生物医学研究界开发工具，特别是发现在细胞、组织和生物体正常或异常功能期间发生改变的蛋白质。这个蛋白质发现领域的术语是蛋白质组学。世界各地每年都要分析数十万个蛋白质组学样本。这些创新将大大有利于生物医学研究界。这些工具将使科学家了解复杂的过程，如微生物组如何影响行为，基因突变如何影响发育，以及癌细胞如何在化疗后改变其行为。这些工具可以帮助解决的问题数量是无限的。所有主要的研究机构都有蛋白质组学设施，为数十到数百名研究人员提供服务。这些工具将被单独的研究实验室和蛋白质组学核心机构，以及合同研究机构和制药公司使用。这个I-Corps项目解决了蛋白质组学领域的技术需求。很大一部分蛋白质组学样本涉及到通过一种称为凝胶电泳的过程将不同蛋白质的复杂混合物分离成单个蛋白质物种，在凝胶材料的薄板中，电流通过大小和电荷来分离蛋白质。这项工作集中于两个未得到满足的关键需求。首先是提高电泳凝胶中蛋白质的检测灵敏度。传统的检测仪器可以检测到超过1000倍浓度范围的蛋白质，但蛋白质通常存在于超过100万倍浓度范围的细胞中。这里开发的设备能够检测超过一百万倍浓度范围的蛋白质。下一个未满足的需求是有效地将蛋白质从凝胶转移到用于化学表征蛋白质的质谱仪上。这里正在开发的方法将大大提高这一过程的吞吐量。

The broader impact/commercial potential of this I-Corps project focuses on developing tools for the biomedical research community, in particular the discovery of proteins that are altered during the normal or abnormal functioning of cells, tissues and organisms. The term for this protein discovery field is proteomics. Hundreds of thousands of proteomics samples are analyzed around the world annually. These innovations will significantly benefit the biomedical research community. These tools will allow scientists to understand complex processes such as how the microbiome affects behavior, how development is affected by genetic mutations, and how cancer cells change their behavior upon chemotherapy. The number of questions these tools can help address is limitless. All major research institutions have proteomics facilities that serve dozens to hundreds of researchers. These tools will be used both by individual research labs and proteomics core facilities, as well as contract research facilities and pharma companies.This I-Corps project addresses technological needs in the field of proteomics. A very large fraction of proteomics samples involve separating complex mixtures of different proteins into individual protein species by a process called gel electrophoresis, where electric currents are used to separate proteins by size and charge in thin slabs of gel material. This work concentrates on two key unmet needs. First is improving the detection sensitivity of proteins within electrophoresis gels. Convention detection instruments can detect proteins over a 1,000-fold concentration range, but proteins normally exist in cells over a million-fold range. The device developed here is capable of detecting proteins over a million-fold concentration range. The next unmet need is to efficiently transfer proteins from gels to a mass spectrometer, which is used to chemically characterize proteins. The method under development here will greatly increase the throughput of this process.