New analytical methods for global and targeted metabolomics

全球和靶向代谢组学的新分析方法

基本信息

  • 批准号:
    RGPIN-2019-06973
  • 负责人:
  • 金额:
    $ 2.11万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2021
  • 资助国家:
    加拿大
  • 起止时间:
    2021-01-01 至 2022-12-31
  • 项目状态:
    已结题

项目摘要

The existing analytical approaches for comprehensive study of hundreds or thousands of metabolites in a single analysis are currently underdeveloped, better-suited for medium to high-abundance stable metabolites and lack adequate validation and quality control procedures, which can in turn lead to erroneous biological conclusions. The long-term objective of the proposed research program is to improve analytical methods in both global and targeted metabolomics with the primary focus on improving the detection and identification of low abundance and unstable metabolites in biological fluids and tissues using high-resolution mass spectrometry. To achieve this objective, we will examine systematically ionic liquids to identify the most useful new extraction materials in metabolomics by liquid chromatography - mass spectrometry (LC-MS). In particular, we will investigate our recent exciting finding that PF6 ionic lipids are suitable for lipid removal and may represent a new class of lipid clarification agents. We will also further refine and miniaturize our sequential extraction protocols to subdivide a complex metabolome into lipid, anion, zwitterion, cation and neutral fractions. Secondly, many hormone peptides are currently detected by poor quality immunoassays relying on polyclonal antibodies because sufficiently sensitive and accurate MS methods do not yet exist. We will develop novel highly sensitive assays for these challenging analytes by combining solid-phase microextraction (SPME), nano LC and state-of-the-art derivatization strategies to achieve limits of detection suitable for their detection in biofluids. Finally, we will expand our research program for unstable metabolites, such as hormone peptides, oxylipins, and thiols, by designing biobanking devices that can preserve these important classes of metabolites and by identifying newly discovered unstable metabolites. The innovative analytical techniques, devices and methods developed in this program will play a critical role to improve both targeted and untargeted metabolomics, while our ultra-sensitive LC-MS platfrom will provide breakthrough technology for hormone peptide analysis. This research program will answer important questions including how (i) to customize emerging materials to improve metabolite coverage over classical approaches, (ii) to miniaturize our new sequential extraction protocols to render them suitable for deep mining of the metabolome even in sample-limited situations, and (iii) to design new analytical methods and devices for preservation and analysis of unstable metabolites, especially hormone peptides and metabolites involved in oxidative stress and inflammation. Collectively, these approaches will aid in rational design and selection of metabolomics methods and discovery of previously-uncharacterized metabolites, thus presenting an important and critically-needed contribution to the field of analytical metabolomics.
现有的在一次分析中对数百或数千种代谢物进行综合研究的分析方法目前还不发达,更适合于中等至高丰度的稳定代谢物,并且缺乏足够的验证和质量控制程序,这反过来又会导致错误的生物学结论。拟议研究计划的长期目标是改进全球和目标代谢组学的分析方法,主要重点是使用高分辨率质谱法改进生物液体和组织中低丰度和不稳定代谢物的检测和鉴定。 为了实现这一目标,我们将系统地研究离子液体,以确定最有用的新提取材料的代谢组学液相色谱-质谱(LC-MS)。特别是,我们将研究我们最近令人兴奋的发现,PF 6离子脂质适合于脂质去除,并可能代表一类新的脂质澄清剂。我们还将进一步完善和优化我们的连续提取方案,将复杂的代谢组细分为脂质、阴离子、两性离子、阳离子和中性组分。其次,目前许多激素肽是通过依赖于多克隆抗体的低质量免疫测定来检测的,因为还不存在足够灵敏和准确的MS方法。我们将开发新的高灵敏度的检测这些具有挑战性的分析物相结合的固相微萃取(SPME),纳米LC和国家的最先进的衍生化策略,以实现检测限适合他们在生物流体中的检测。最后,我们将扩大我们的研究计划,为不稳定的代谢物,如激素肽,oxlipins和硫醇,通过设计生物银行设备,可以保存这些重要类别的代谢物,并确定新发现的不稳定的代谢物。 该项目开发的创新分析技术、设备和方法将在改善靶向和非靶向代谢组学方面发挥关键作用,而我们的超灵敏LC-MS平台将为激素肽分析提供突破性技术。这项研究计划将回答重要的问题,包括如何(i)定制新兴材料,以提高代谢物覆盖率超过经典方法,(ii)优化我们的新的顺序提取方案,使其适用于代谢物组的深度挖掘,即使在样品有限的情况下,和(iii)设计新的分析方法和设备,用于保存和分析不稳定的代谢物,尤其是参与氧化应激和炎症的激素肽和代谢物。总的来说,这些方法将有助于合理设计和选择代谢组学方法和发现以前未表征的代谢物,从而为分析代谢组学领域做出重要和急需的贡献。

项目成果

期刊论文数量(0)
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Vuckovic, Dajana其他文献

Solid-Phase Microextraction Method Development
  • DOI:
    10.1016/b978-0-12-416017-0.00007-3
  • 发表时间:
    2012-01-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kudlejova, Lucie;Risticevic, Sanja;Vuckovic, Dajana
  • 通讯作者:
    Vuckovic, Dajana
Systematic Evaluation of Solid-Phase Microextraction Coatings for Untargeted Metabolomic Profiling of Biological Fluids by Liquid Chromatography-Mass Spectrometry
  • DOI:
    10.1021/ac102614v
  • 发表时间:
    2011-03-15
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Vuckovic, Dajana;Pawliszyn, Janusz
  • 通讯作者:
    Pawliszyn, Janusz
Automated study of ligand-receptor binding using solid-phase microextraction
Target Identification by Chromatographic Co-elution: Monitoring of Drug-Protein Interactions without Immobilization or Chemical Derivatization
  • DOI:
    10.1074/mcp.m111.016642
  • 发表时间:
    2012-07-01
  • 期刊:
  • 影响因子:
    7
  • 作者:
    Chan, Janet N. Y.;Vuckovic, Dajana;Emili, Andrew
  • 通讯作者:
    Emili, Andrew
Determination of tranexamic acid concentration by solid phase microextraction and liquid chromatography-tandem mass spectrometry: First step to in vivo analysis

Vuckovic, Dajana的其他文献

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{{ truncateString('Vuckovic, Dajana', 18)}}的其他基金

New analytical methods for global and targeted metabolomics
全局和靶向代谢组学的新分析方法
  • 批准号:
    RGPIN-2019-06973
  • 财政年份:
    2022
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
New analytical methods for global and targeted metabolomics
全球和靶向代谢组学的新分析方法
  • 批准号:
    RGPIN-2019-06973
  • 财政年份:
    2020
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
New analytical methods for global and targeted metabolomics
全球和靶向代谢组学的新分析方法
  • 批准号:
    RGPIN-2019-06973
  • 财政年份:
    2019
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
New analytical methods for studying low abundance metabolome
研究低丰度代谢组的新分析方法
  • 批准号:
    435814-2013
  • 财政年份:
    2018
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
New analytical methods for studying low abundance metabolome
研究低丰度代谢组的新分析方法
  • 批准号:
    435814-2013
  • 财政年份:
    2017
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
New analytical methods for studying low abundance metabolome
研究低丰度代谢组的新分析方法
  • 批准号:
    435814-2013
  • 财政年份:
    2016
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
High-resolution mass spectrometer for metabolomics and lipidomics
用于代谢组学和脂质组学的高分辨率质谱仪
  • 批准号:
    RTI-2016-00596
  • 财政年份:
    2015
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Research Tools and Instruments
New analytical methods for studying low abundance metabolome
研究低丰度代谢组的新分析方法
  • 批准号:
    435814-2013
  • 财政年份:
    2015
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
New analytical methods for studying low abundance metabolome
研究低丰度代谢组的新分析方法
  • 批准号:
    435814-2013
  • 财政年份:
    2014
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Discovery Grants Program - Individual
Liquid-handler for high-throughput metabolomics of biological fluids
用于生物体液高通量代谢组学的液体处理器
  • 批准号:
    472731-2015
  • 财政年份:
    2014
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Research Tools and Instruments - Category 1 (<$150,000)

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全局和靶向代谢组学的新分析方法
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