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Solid-state nanopore-based MMP/ADAM profiling for early cancer detection

Solid-state nanopore-based MMP/ADAM profiling for early cancer detection
基于固态纳米孔的 MMP/ADAM 分析用于早期癌症检测
批准号:
1708596
负责人:
Xiyun Guan
金额:
$36.0万
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-08-15 至 2021-07-31

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中文摘要
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英文摘要
Non-technical:This award by the Biomaterials Program in the Division of Materials Research to the Illinois Institute of Technology is to develop next-generation of biomaterials based on two groups of biocatalysts, namely MMPs (matrix metalloproteinases) and ADAMs (a disintegrin and metalloproteinases) for possible applications in sensing and other technologies. MMPs and ADAMs are enzymes that are responsible for extracellular matrix degradation and tissue remodeling, and play important roles in various biological, physiological, and pathological processes. They are currently under intensive investigation as novel biomarkers and potential therapeutic targets for the early detection and possible treatment of human cancers. However, the current MMP/ADAM assays suffer from low specificity and poor selectivity, which results in their limited utility for any applications. This project offers a new label-free strategy, which combines nanopore sensing and substrate-based proteinase assay, to accomplish highly selective and sensitive measurement of the activity of MMPs/ADAMs. The proposed studies are expected to lead to a better understanding of molecular and ionic transport, as well as to develop a versatile tool for various applications, including biosensing, studying covalent and non-covalent bonding interactions, investigating biomolecular folding and unfolding, and exploring enzyme kinetics. In addition to research, educational and outreach components are also an integral part of this project. The newest research findings from this work will be incorporated in classroom teaching for the benefit of students not directly involved in this research. The PI will recruit undergraduate and graduate students (especially Hispanic and African American minority groups) to participate in the research through established local programs. The PI will disseminate nanopore sensing technology by organizing interdisciplinary symposiums to promote idea exchange and facilitate national & international collaborations among peers and general public. Technical:This project will explore a new strategy to measure the activities of MMPs (matrix metalloproteinases) and ADAMs (a disintegrin and metalloproteinases), and this is accomplished by real-time monitoring of the ionic current modulations caused by the protease-substrate peptide interactions in the nanopore. By taking advantage of both the substrate specificity and the substrate cleavage sites, the nanopore sensor offers a potential to significantly improve the selectivity and accuracy of the MMPs/ADAMs assays. The three objectives of this project will be: 1) to investigate various factors which affect peptide transport in a nano-channel, and gain understanding of the underlying mechanism; 2) to study a simple non-array-based methodology for the multiplex detection and measurement of activities of MMPs/ADAMs to improve assay efficiency, and reduce the sensor manufacturing and assay cost; and 3) to develop a portable solid-state nanopore-based protease detection technique for potential mobile-lab detection of cancer biomarkers for point-of-care applications. The studies are expected to have broad impact on a variety of areas where analyses of proteases are important, such as biology, nanotechnology, pharmaceutical industry, toxicology in general, and biosensing. The components of the educational plan include: incorporation of research findings into classroom teaching; active recruitment of undergraduate and graduate students from underrepresented groups; establishment of a summer scholar research program for high school students; and organizing interdisciplinary symposiums. This interdisciplinary project offers an ideal training opportunity for all participants, particularly with respect to future career opportunities.
期刊论文(13)
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DOI: 10.1021/acsabm.8b00689
发表时间: 2019-01-22
期刊: ACS APPLIED BIO MATERIALS
影响因子: 4.7
作者: [Chen, Xiaohan, Zhang, Youwen, Guan, Xiyun]
通讯作者: Guan, Xiyun
Investigation of Protein Transport in Functionalized Polymeric Nanopores
  • 批准号:
    2345813
  • 项目类别:
    Standard Grant
  • 资助金额:
    $37.11万
  • 财政年份:
    2023
  • 负责人:
    Xiyun Guan
  • 依托单位:
Investigation of Protein Transport in Functionalized Polymeric Nanopores
  • 批准号:
    2203763
  • 项目类别:
    Standard Grant
  • 资助金额:
    $37.11万
  • 财政年份:
    2022
  • 负责人:
    Xiyun Guan
  • 依托单位:
国内基金
海外基金
Simulation and certification of the ground state of many-body systems on quantum simulators
  • 批准号:
    --
  • 项目类别:
    --
  • 资助金额:
    40万元
  • 批准年份:
    2020
  • 负责人:
    Abolfazl Bayat
  • 依托单位:
Cortical control of internal state in the insular cortex-claustrum region
微波有源Scattering dark state粒子的理论及应用研究
  • 批准号:
    61701437
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    28.0万元
  • 批准年份:
    2017
  • 负责人:
    李欢
  • 依托单位:
超导量子器件中关于量子计算、电路量子电动力学和退相干的研究
  • 批准号:
    11174248
  • 项目类别:
    面上项目
  • 资助金额:
    75.0万元
  • 批准年份:
    2011
  • 负责人:
    王浩华
  • 依托单位: