Using calorespirometry to assemble a complete picture of acute hypoxic metabolic depression in fishes

使用热量呼吸测定法来绘制鱼类急性缺氧代谢抑制的完整图像

基本信息

  • 批准号:
    RGPIN-2021-03109
  • 负责人:
  • 金额:
    $ 2.77万
  • 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:
    2022
  • 资助国家:
    加拿大
  • 起止时间:
    2022-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

Human practices are rendering the world's aquatic environments increasingly hypoxic (low O2). This threatens the resident animals because O2 is required to supply sufficient quantities of cellular energy (ATP) to meet the animals' high metabolic demands. However, many animals, especially fishes, are adapted to environments that already experience hypoxia, and we can look to the tolerance strategies of these species to understand what might facilitate or hinder an animal's ability to adapt to a changing world. A highly effective strategy for tolerating hypoxia is metabolic depression (MD), a regulated reduction of metabolic rate - and thus the supply and use of ATP - below resting levels. Not all fishes can induce hypoxic MD, but those that can tend to be highly tolerant of hypoxia. Some of the downregulated cellular ATP-supply and -use processes that contribute to hypoxic MD have been investigated in isolation; however, the upstream signal that induces their downregulation and the manner by which their modulation is linked via time and O2 level (PO2) remain unknown. This Discovery Grant will build significantly upon my previous work to test the overarching hypothesis that diminished hemoglobin (Hb)-mediated O2 supply to the tissues serves as the initial signal for hypoxic MD in fish. Specifically, when water PO2 becomes too low for Hb to bind and deliver sufficient quantities of O2 to the tissues, those tissues induce MD, including the arrest of aerobic and anaerobic ATP-supply pathways and the downregulation of ATP-use processes. Through 4 hypothesis-driven projects, the work will first investigate the role of Hb in hypoxic MD induction through experiments involving calorespirometry and the manipulation of Hb-O2 affinity. Second, it will determine how cellular PO2 affects aerobic ATP supply pathways using high resolution respirometry. Third, it will investigate how the arrest of ATP-supply and -use processes are linked as a function of time and PO2 using cultured tissue cells. And fourth, it will investigate at the cellular level why some species are unable to induce hypoxic MD. The expected outcome of this work is a better understanding of what signals hypoxic MD induction, how its cellular mechanisms are linked sequentially, and what cellular mechanisms differ between species that do and do not use hypoxic MD. Currently, these are unknowns. The proposed work will train 5 graduate (4 MSc, 1 PhD) and 6 undergraduate students, providing them with widely applicable research and analytical skills. Additionally, it will improve our understanding of animal responses to aquatic hypoxia, a phenomenon that is increasing globally (incl. Canada) and threatens innumerable fish populations. Recent work indicates that hypoxic MD may be a rapidly evolved strategy for tolerating hypoxia. Understanding its proximate and ultimate mechanisms may benefit predictive models for identifying potentially vulnerable species and conservation efforts for protecting them.
人类的做法正在使世界上的水生环境变得越来越低氧(低氧气)。这对栖息的动物构成了威胁,因为O2需要提供足够数量的细胞能量(ATP)来满足动物的高代谢需求。然而,许多动物,特别是鱼类,已经适应了已经经历缺氧的环境,我们可以研究这些物种的耐受策略,以了解什么可能促进或阻碍动物适应不断变化的世界的能力。耐受低氧的一种高效策略是代谢抑制(MD),这是一种代谢速率的调节降低--从而使ATP的供应和使用--低于静息水平。并不是所有的鱼都能引起缺氧性MD,但那些可以高度耐缺氧的鱼。一些导致缺氧性MD的细胞ATP供应和使用过程已经被孤立地研究;然而,诱导它们下调的上游信号以及它们的调节方式通过时间和O2水平(PO2)联系在一起的方式仍然未知。这项发现拨款将大大建立在我以前工作的基础上,以测试最重要的假设,即减少血红蛋白(Hb)介导的组织氧气供应是鱼类缺氧性MD的初始信号。具体地说,当水中的PO2变得太低,Hb无法结合并向组织输送足够数量的O2时,这些组织就会诱发MD,包括有氧和无氧ATP供应途径的停止以及ATP使用过程的下调。通过4个假设驱动的项目,这项工作将首先通过实验研究Hb在低氧性MD诱导中的作用,实验涉及量热呼吸和Hb-O2亲和力的操纵。其次,它将使用高分辨率呼吸测量法确定细胞氧合氧对有氧ATP供应途径的影响。第三,它将利用培养的组织细胞,研究ATP供应和使用过程的停止是如何作为时间和PO2的函数联系在一起的。第四,它将在细胞水平上研究为什么一些物种无法诱导缺氧性MD。这项工作的预期结果是更好地理解低氧MD诱导的信号,其细胞机制是如何顺序连接的,以及使用和不使用低氧MD的物种之间有什么细胞机制不同。目前,这些都是未知的。拟议的工作将培养5名研究生(4名硕士,1名博士)和6名本科生,为他们提供广泛适用的研究和分析技能。此外,它将提高我们对动物对水生缺氧的反应的理解,这种现象在全球范围内正在增加(包括。加拿大),并威胁到无数的鱼类种群。最近的研究表明,缺氧性MD可能是一种快速进化的耐缺氧策略。了解其最近和最终的机制可能有助于建立预测模型,以识别潜在的脆弱物种,并为保护它们而进行保护努力。

项目成果

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Regan, Matthew其他文献

Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death.
  • DOI:
    10.1038/s41591-022-02142-1
  • 发表时间:
    2023-01
  • 期刊:
  • 影响因子:
    82.9
  • 作者:
    Byrne, Alicia B.;Arts, Peer;Ha, Thuong T.;Kassahn, Karin S.;Pais, Lynn S.;O'Donnell-Luria, Anne;Babic, Milena;Frank, Mahalia S. B.;Feng, Jinghua;Wang, Paul;Lawrence, David M.;Eshraghi, Leila;Arriola, Luis;Toubia, John;Nguyen, Hung;McGillivray, George;Pinner, Jason;McKenzie, Fiona;Morrow, Rebecca;Lipsett, Jill;Manton, Nick;Khong, T. Yee;Moore, Lynette;Liebelt, Jan E.;Schreiber, Andreas W.;King-Smith, Sarah L.;Hardy, Tristan S. E.;Jackson, Matilda R.;Barnett, Christopher P.;Scott, Hamish S.;Aguet, Francois;Arachchi, Harindra M.;Austin-Tse, Christina A.;Babb, Larry;Baxter, Samantha M.;Brand, Harrison;Byrne, Alicia B.;Chang, Jaime;Chao, Katherine R.;Collins, Ryan L.;Cummings, Beryl;Delano, Kayla;DiTroia, Stephanie P.;England, Eleina;Evangelista, Emily;Everett, Selin;Francioli, Laurent C.;Fu, Jack;Ganesh, Vijay S.;Garimella, Kiran, V;Gauthier, Laura D.;Goodrich, Julia K.;Gudmundsson, Sanna;Hall, Stacey J.;Huang, Yongqing;Jahl, Steve;Laricchia, Kristen M.;Larkin, Kathryn E.;Lek, Monkol;Lemire, Gabrielle;Lipson, Rachel B.;Lovgren, Alysia Kern;MacArthur, Daniel G.;Mangilog, Brian E.;Mano, Stacy;Marshall, Jamie L.;Mullen, Thomas E.;Nguyen, Kevin K.;O'Heir, Emily;O'Leary, Melanie C.;Osei-Owusu, Ikeoluwa A.;Pais, Lynn S.;Chavez, Jorge Perez de Acha;Pierce-Hoffman, Emma;Rehm, Heidi L.;Serrano, Milan;Singer-Berk, Moriel;Snow, Hana;Solomonson, Matthew;Son, Rachel G.;Sveden, Abigail;Talkowski, Michael;Tiao, Grace;Udler, Miriam S.;Valivullah, Zaheer;Valkanas, Elise;VanNoy, Grace E.;Wang, Qingbo S.;Watts, Nicholas A.;Weisburd, Ben;Williamson, Clara E.;Wilson, Michael W.;Witzgall, Lauren;Wojcik, Monica H.;Wong, Isaac;Wood, Jordan C.;Zhang, Shifa;Abeysuriya, Disna;Ades, Lesley C.;Amor, David J.;Arbuckle, Susan;Bakshi, Madhura;Barnete, Christopher P.;Berry, Bligh;Boughtwood, Tiffany;Bournazos, Adam;Bray, Alessandra;Chan, Fiona;Chan, Yuen;Chung, Clara;Clark, Jonathan;Collett, Jackie;Colley, Alison;Collins, Felicity;Cooper, Sandra;Corbett, Mark A.;Dahlstrom, Jane E.;Dargaville, Peter;Davies, Janene;Davis, Tenielle;Dearman, Jarrad;Dissanayake, Jayanthi;Dobbins, Julia;Doyle, Helen;Dubowsky, Andrew;Edwards, Matt;Ewans, Lisa J.;Fadia, Mitali;Fennell, Andrew;Finlay, Ken;French, Andrew;Friend, Kathryn;Gardner, Alison E.;Gecz, Jozef;Graf, Nicole;Haan, Eric A.;Hollingsworth, Georgina;Horton, Ari E.;Howting, Denise;Hunter, Matthew F.;Jevon, Gareth;Kamien, Benjamin;Kennedy, Debra;Khong, T. Yee;Krivanek, Michael;Kroes, Thessa;Krzesinski, Emma, I;Kwan, Edward;Lau, Stephanie;LeBlanc, Shannon;Liebelt, Jan;Lindsey-Temple, Suzanna;Lipsett, Jill;Loo, Christine K. C.;Low, Julia;Mallawaarachchi, Amali;Manton, Nick;Matsika, Admire;Mattiske, Tessa;McGaughran, Julie;McGillivray, George;McGregor, Lesley;McKenzie, Fiona;Mittal, Namita;Moghimi, Ali;Moore, Lynette;Albayrak, Hatice Mutlu;Ng, Jessica;Nicholl, Jillian;Pachter, Nicholas;Papadimitriou, John;Parker, Renae;Parsons, Sarah;Patel, Chirag;Pawlowski, Rhonda;Perez-Jurado, Luis A.;Pinner, Jason R.;Politis, Katerina;Poulton, Cathryn;Power, Theresa;Quinn, Michael;Rajagopalan, Sulekha;Regan, Matthew;Rodgers, Jonathan;Rorke, Steuart;Sachdev, Rani;Sallevelt, Suzanne;Sandaradura, Sarah A.;Shamassi, Maryam;Shamon, Roshan;Sherburn, Isabella;Slee, Ennie;Solinas, Annalisa;Sugo, Ella;Thompson, Elizabeth;Tripathy, Sagarika;Vasudevan, Anand;Vazquez, Melisa;Verma, Kunal;Viki, Mthulisi;Wallis, Mathew;Webber, Dani L.;Weber, Martin;Whale, Karen;Wilson, Meredith;Worgan, Lisa;Yu, Sui
  • 通讯作者:
    Yu, Sui

Regan, Matthew的其他文献

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{{ truncateString('Regan, Matthew', 18)}}的其他基金

Using calorespirometry to assemble a complete picture of acute hypoxic metabolic depression in fishes
使用热量呼吸测定法来绘制鱼类急性缺氧代谢抑制的完整图像
  • 批准号:
    RGPIN-2021-03109
  • 财政年份:
    2021
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Discovery Grants Program - Individual
Using calorespirometry to assemble a complete picture of acute hypoxic metabolic depression in fishes
使用热量呼吸测定法来绘制鱼类急性缺氧代谢抑制的完整图像
  • 批准号:
    DGECR-2021-00153
  • 财政年份:
    2021
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Discovery Launch Supplement
Integrating the microbiome into the hibernator's metabolic phenotype
将微生物组整合到冬眠者的代谢表型中
  • 批准号:
    532597-2019
  • 财政年份:
    2020
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Postdoctoral Fellowships
Integrating the microbiome into the hibernator's metabolic phenotype
将微生物组整合到冬眠者的代谢表型中
  • 批准号:
    532597-2019
  • 财政年份:
    2019
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Postdoctoral Fellowships
Integrating the microbiome into the hibernator's metabolic phenotype
将微生物组整合到冬眠者的代谢表型中
  • 批准号:
    532597-2019
  • 财政年份:
    2018
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Postdoctoral Fellowships
The role of intracellular ph regulation in the evolution of air-breathing
细胞内pH调节在空气呼吸进化中的作用
  • 批准号:
    389031-2010
  • 财政年份:
    2012
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The role of intracellular ph regulation in the evolution of air-breathing
细胞内pH调节在空气呼吸进化中的作用
  • 批准号:
    389031-2010
  • 财政年份:
    2011
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The role of intracellular ph regulation in the evolution of air-breathing
细胞内pH调节在空气呼吸进化中的作用
  • 批准号:
    389031-2010
  • 财政年份:
    2010
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Postgraduate Scholarships - Doctoral

相似海外基金

Using calorespirometry to assemble a complete picture of acute hypoxic metabolic depression in fishes
使用热量呼吸测定法来绘制鱼类急性缺氧代谢抑制的完整图像
  • 批准号:
    RGPIN-2021-03109
  • 财政年份:
    2021
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Discovery Grants Program - Individual
Using calorespirometry to assemble a complete picture of acute hypoxic metabolic depression in fishes
使用热量呼吸测定法来绘制鱼类急性缺氧代谢抑制的完整图像
  • 批准号:
    DGECR-2021-00153
  • 财政年份:
    2021
  • 资助金额:
    $ 2.77万
  • 项目类别:
    Discovery Launch Supplement
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