Unravelling the Lipidome of Idiopathic Pulmonary ... Idiopathic Pulmonary Fibrosis and its Spatial Distribution

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  • Unravelling the Lipidome of

    Idiopathic Pulmonary Fibrosis and its

    Spatial Distribution using High

    Resolution Mass Spectrometry

    by

    Shabarinath Mathoosoothenen Nambiar

    BSc. (Hons)

    This thesis is presented for the degree of Doctor of Philosophy at

    the School of Veterinary and Life Sciences, Murdoch University,

    Perth, Western Australia

    2018

  • ii

    A journey that took my breath away

  • iii

    Declaration

    I declare that this thesis is my own account of my research and contains, as its main

    content, work that has not been previously submitted for a degree at any tertiary

    educational institution.

    In addition, I claim the majority of authorship for each manuscript presented in this thesis.

    In doing so, I declare that the co-authors listed in the “Statement of Authorship”

    contributed by critically evaluating and commenting on the relevant manuscript.

    Shabarinath Mathoosoothenen Nambiar

  • iv

    Statement of Authorship for Chapter 1

    Title of Manuscript Metabolomics in chronic lung diseases: a practical review for clinicians

    Manuscript Status  Published  Accepted for publication

     Submitted for review

     Ready for submission

    Manuscript Details The manuscript was submitted to Respirology (Impact factor: 4.407) and is

    included as Chapter 1 in this thesis.

    Principal Author

    Name of Principal Author Shabarinath Nambiar

    Contribution to the Manuscript Critically reviewed the literature, prepared the manuscript and

    acted as corresponding author.

    Signature

    Date 29/11/2018

    Co-Authors

    By signing this Statement of Authorship, each co-author certifies that:

    a) the candidate’s stated contribution to the manuscript is accurate (as detailed above); b) the co-author’s stated contribution to the manuscript is accurate (as per below); and c) permission is granted for the candidate to include the manuscript in this thesis.

    Name of Co-Author Bong Sze How

    Contribution to the Manuscript Proposed the concept, critically reviewed and approved the final

    version of the manuscript.

    Signature

    Date 29/11/2018

    Name of Co-Author Robert Trengove

    Contribution to the Manuscript Reviewed and evaluated the manuscript.

    Signature

    Date 29/11/2018

    Name of Co-Author Joel Gummer

    Contribution to the Manuscript Reviewed and evaluated the manuscript.

    Signature

    Date 23/11/2018

    Name of Co-Author Yuben Moodley

    Contribution to the Manuscript Proposed the review and evaluated the manuscript.

    Signature

    Date 29/11/2018

  • v

    Statement of Authorship for Chapter 2

    Title of Manuscript Untargeted metabolomics of human plasma reveals unique lipid markers in

    COPD and IPF patients

    Manuscript Status  Published  Accepted for publication

     Submitted for review  Ready for submission

    Manuscript Details The manuscript will be submitted to Respirology (Impact factor: 4.407) and

    is included as Chapter 2 in this thesis.

    Principal Author

    Name of Principal Author Shabarinath Nambiar

    Contribution to the Manuscript Processed and interpreted the data. Prepared the manuscript.

    Signature

    Date 29/11/2018

    Co-Authors

    By signing this Statement of Authorship, each co-author certifies that:

    d) the candidate’s stated contribution to the manuscript is accurate (as detailed above); e) the co-author’s stated contribution to the manuscript is accurate (as per below); and f) permission is granted for the candidate to include the manuscript in this thesis.

    Name of Co-Author Bong Sze How

    Contribution to the Manuscript Helped evaluate and critically reviewed the manuscript.

    Signature

    Date 29/11/2018

    Name of Co-Author Catherine Rawlinson

    Contribution to the Manuscript Performed sample preparation and instrumental analysis on all

    samples.

    Signature

    Date 26/11/2018

    Name of Co-Author Joel Gummer

    Contribution to the Manuscript Supervised the project and edited the manuscript.

    Signature

    Date 23/11/2018

    Name of Co-Author Yuben Moodley

    Contribution to the Manuscript Provided the samples and supervised the development of work.

    Signature

    Date 29/11/2018

  • vi

    Name of Co-Author Robert Trengove

    Contribution to the Manuscript Supervised the project development, helped in data interpretation

    and manuscript evaluation.

    Signature

    Date 29/11/2018

  • vii

    Statement of Authorship for Chapter 3

    Title of Manuscript SONAR enhances the specificity of unbiased lipid plasma profiling of

    idiopathic pulmonary fibrosis

    Manuscript Status  Published  Accepted for publication

     Submitted for review  Ready for submission

    Manuscript Details The manuscript will be submitted to Journal of Lipid Research (Impact factor:

    5.559) and is included as Chapter 3 in this thesis.

    Principal Author

    Name of Principal Author Shabarinath Nambiar

    Contribution to the Manuscript Performed sample preparation and analyses, processed and

    interpreted the data. Prepared the manuscript.

    Signature

    Date 29/11/2018

    Co-Authors

    By signing this Statement of Authorship, each co-author certifies that:

    g) the candidate’s stated contribution to the manuscript is accurate (as detailed above); h) the co-author’s stated contribution to the manuscript is accurate (as per below); and i) permission is granted for the candidate to include the manuscript in this thesis.

    Name of Co-Author Robert Trengove

    Contribution to the Manuscript Evaluated and commented on the manuscript.

    Signature

    Date 29/112018

    Name of Co-Author Adam King

    Contribution to the Manuscript Helped with the analytical and data processing workflows.

    Signature

    Date 28/11/2018

    Name of Co-Author Yuben Moodley

    Contribution to the Manuscript Provided the samples and supervised the project.

    Signature

    Date 29/11/2018

    Name of Co-Author Bong Sze How

    Contribution to the Manuscript Supervised the analytical workflow, critically reviewed the

    manuscript.

    Signature

    Date 29/11/2018

  • viii

    Statement of Authorship for Chapter 4

    Title of Manuscript MALDI-mass spectrometry imaging by freeze-spot deposition of the matrix

    Manuscript Status  Published  Accepted for publication

     Submitted for review  Ready for submission

    Manuscript Details The manuscript will be submitted to Analytical Chemistry (Impact factor:

    6.042) and is included as Chapter 4 in this thesis.

    Principal Author

    Name of Principal Author Shabarinath Nambiar

    Contribution to the Manuscript Performed sample preparation and analyses, processed and

    interpreted the data. Prepared the manuscript.

    Signature

    Date 29/11/2018

    Co-Authors

    By signing this Statement of Authorship, each co-author certifies that:

    j) the candidate’s stated contribution to the manuscript is accurate (as detailed above); k) the co-author’s stated contribution to the manuscript is accurate (as per below); and l) permission is granted for the candidate to include the manuscript in this thesis.

    Name of Co-Author Robert Trengove

    Contribution to the Manuscript Supervised project development and helped evaluate the

    manuscript.

    Signature

    Date 29/11/2018

    Name of Co-Author Joel Gummer

    Contribution to the Manuscript Supervised the project concept and design. Critically reviewed

    the manuscript.

    Signature

    Date 23/11/2018

  • ix

    Statement of Authorship for Chapter 5

    Title of Manuscript Optimisation of MALDI-MSI matrix improves spatial resolution of lipid

    species in fibrotic lung tissue

    Manuscript Status  Published  Accepted for publication

     Submitted for review  Ready for submission

    Manuscript Details The manuscript will be submitted to Progress in Lipid Research (Impact

    factor: 8.435) and is included as Chapter 5 in this thesis.

    Principal Author

    Name of Principal Author Shabarinath Nambiar

    Contribution to the Manuscript Developed project concept and design, performed sample

    preparation and analyses, processed and interpreted the data.

    Prepared the manuscript.

    Signature

    Date 29/11/2018

    Co-Authors

    By signing this Statement of Authorship, each co-author certifies that:

    m) the candidate’s stated contribution to the manuscript is accurate (as detailed above); n) the co-author’s stated contribution to the manuscript is accurate (as per below); and o) permission is granted for the candidate to include the manuscript in this thesis.

    Name of Co-Author Robert Trengove

    Contribution to the Manuscript Reviewed and evaluated the manuscript.