Degrees

PhD in Chemical Biology
Studies on the biosynthesis of non-ribosomal peptides
University of Cambridge, UK

Masters in Chemistry
University of Oxford, UK

Vita

2018 - 2020
Turing Fellow
Alan Turing Institute London

2015 - date
Fellow of Natural Sciences
Downing College

2015 - date
Senior Research Associate
Cancer Research UK Cambridge Research Institute

2013 - 2014
Research Associate
Cancer Research UK Cambridge Research Institute

2009 - 2013
Career Development Fellow
MRC Laboratory of Molecular Biology

2005 - 2009
PhD student
Deparment of Chemistry, University of Cambridge, UK.
Advisors: Dr. J. Spencer and Dr. F. Leeper

Professional Memberships

2015 Fellow of the Higher Education Academy

2014 Member Biochemical Society

2009 Member Royal Society of Chemistry

Photo of Andrew Holding

Awards and fellowships

2018 Turing Fellowship, Alan Turing Institute

2017 Thomas Jefferson Visiting Fellow at University of Virginia

2017 CRUK Research Travel Award

2015 CRUK Rising Star in Research Engagement Prize

2015 Fellow Downing College

2014 Unltd Try-It Award

2013 College Lecturer and Bye-Fellow Downing College

2012 Wellcome Trust People Award

2012 British Mass Spectrometry Society Travel Award

2012 MRC Award via the Special Awards Scheme for contributions to the MRC

2012 British Science Association Media Fellowship

2011 UnLtd Catalyst Award for Social Entrepreneurship

2009 MRC Career Development Fellowship

2005 BBSRC PhD Studentship


Published Research

Journal Articles

  1. Andrew N. Holding*, Amy E. Cullen and Florian Markowetz (2018)
    Genome-wide Estrogen Receptor-alpha activation is sustained, not cyclical
    Preprint. [bioRxiv]

  2. Andrew N. Holding*, Federico M. Giorgi, Amanda Donnelly, Amy E. Cullen, Luke A. Selth and Florian Markowetz (2018)
    Network Dynamics of ER-α activation reveals reprogramming of GRHL2
    Preprint. [bioRxiv]

  3. Euan S. Polson, Verena B. Kuchler, Christopher Abbosh, Edith M. Ross, Ryan K. Mathew, Hester A. Beard, Bárbara da Silva, Andrew N. Holding, Stephane Ballereau, Eulashini Chuntharpursat-Bon, Jennifer Williams, Hollie B. S. Griffiths, Hao Shao, Anjana Patel, Adam J. Davies, Alastair Droop, Paul Chumas, Susan C. Short, Mihaela Lorger, Jason E. Gestwicki, Lee D. Roberts, Robin. S Bon, Simon J. Allison, Shoutian Zhu, Florian Markowetz, Heiko Wurdak (2018)
    KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice
    Science translational medicine, 10, 454. [PubMed]

  4. Evangelia K. Papachristou, Kamal Kishore1, Andrew N. Holding1, … , Rasmus Siersbaek, Clive S. D’Santos and Jason S. Carroll (2018)
    A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes
    Nature Communications, 9, 2311. [PubMed]

  5. Michael J. Guertin, Amy E. Cullen, Florian Markowetz and Andrew N. Holding* (2018)
    Parallel Factor ChIP Provides Essential Internal Control for Quantitative Differential ChIP-Seq
    Nucleic Acids Research. 46, 12. [PubMed]

  6. Andrew N. Holding* (2015)
    XL–MS: Protein cross-linking coupled with mass spectrometry
    Methods 89. 54-63. [Science Direct]

  7. Jennifer Lee, ShuJing Ding, Thomas B. Walpole, Andrew N. Holding, Martin G. Montgomery, Ian M. Fearnley and John E. Walker (2015)
    Organisation of Subunits in the Membrane Domain of the Bovine F-ATPase Revealed by Covalent Cross-linking.
    J. Biol. Chem. 290. 13308-20. [PubMed]

  8. Andrew N Holding,* Meindert H Lamers, Elaine Stephens and J Mark Skehel (2013)
    Hekate: software suite for the mass spectrometric analysis and three-dimensional visualization of cross-linked protein samples.
    J Proteome Res. 12. 5923-33. [PubMed]

  9. Yang Liu,1 Hannah K Salter, 1 Andrew N Holding, Christopher M Johnson, Elaine Stephens, Peter J Lukavsky, John Wlashaw and Simon L Bullock (2013)
    Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein.
    Genes Dev. 27. 1233-46. [PubMed]

  10. Andrew N Holding,1 Ana Toste Rego,1 Helen Kent and Meindert H Lamers (2013)
    Architecture of the Pol III—clamp—exonuclease complex reveals key roles of the exonuclease subunit in processive DNA synthesis and repair.
    EMBO J. 32. 1334-1343. [Pubmed] [F1000Prime] - recommended as being of special significance.

  11. Andrew N Holding* and Jonathan B Spencer. (2008)
    Investigation into the mechanism of phenolic couplings during the biosynthesis of glycopeptide antibiotics.
    ChemBioChem. 9. 2209-14. [Pubmed]

  12. Helen M O’Hare, Fanglu Huang, Andrew Holding, Oliver W Choroba and Jonathan B Spencer. (2006)
    Conversion of hydroxyphenylpyruvate dioxygenases into hydroxymandelate synthases by directed evolution.
    FEBS Lett. 580. 3445-50. [Pubmed]

1These authors contributed equally to this work.
* Corresponding author.

Oral Presentations

  1. Integrative analysis of ER-α in breast cancer reveals a robust and sustained response to estra-2-diol
    Keynote speaker, Biosciences Symposium, 2018, Essex.
  2. Network Dynamics of ER-α activation reveals reprogramming of GRHL2
    Applied Bioinformatics In Life Sciences, 2018, Leuven, Belgium.
  3. Utilising mass spectrometry for the structural and functional analysis of complex systems in medical research
    Invited speaker, 2016, University of Essex, Colchester, UK.
  4. Visualizing gene regulation: a combined proteomic and genomic approach for the structural analysis of steroid hormone receptor complexes
    Invited speaker, 4th International Congress on Analytical Proteomics, 2015, Lisbon, Portugal.
  5. Bringing Proteogenomics to the study of ER+ breast cancer
    Invited speaker, 2014, MRC Cancer Unit, Cambridge, UK.
  6. Interactions within the E. coli Replisome
    Mini-symposium on Biophysics, 2012, MRC Laboratory of Molecular Biology.
  7. Interactions within the E. coli Replisome
    Proteomics Methods Forum, 2012, Barts Cancer Institue, London, UK.
  8. Cross-linking in mass spectrometry
    Proteomics Methods Forum, 2010, Department of Biochemistry, University of Cambridge.
  9. Cross-linking in mass spectrometry
    Mini-symposium on Biophysics, 2010, MRC Laboratory of Molecular Biology.

Poster Presentations

  1. Parallel Factor ChIP Provides Essential Internal Control for Quantitative Differential ChIP-seq
    M. J. Guertin, A. E. Cullen, F. Markowetz A. N. Holding,
    Cambridge Cancer Centre Symposium, 2017, Cambridge, UK.
  2. ChIP-MS/TMT: a quantative proteomic analysis of steroid hormone receptor activation.
    A. N. Holding, F. Markowetz
    64th ASMS Conference on Mass Spectrometry and Allied Topics, 2016, San Antonio, Texas, USA
  3. Visualising gene regulation: A combined proteomic and genomic approach for the analysis of steroid hormone receptor complexes.
    A. N. Holding, J. C. Carroll, F. Markowetz
    29th Annual Symposium of the Protein Society, Barcelona, Spain
  4. Visualising gene regulation: A combined proteomic and genomic approach for the analysis of steroid hormone receptor complexes.
    A. N. Holding, J. C. Carroll, F. Markowetz
    Cambridge Cancer Centre Symposium, 2015, Cambridge, UK.
  5. Hekate – Software suite for the mass spectrometric analysis & three-dimensional visualization of cross-linked protein samples.
    A. N. Holding, Y. Liu, H. K. Salter, M. L. Lamers, S. L. Bullock, M. J. Skehel
    Postdoctoral Career Development Day, Cancer Research UK, 2014,London, UK
  6. A shared binding site for different cargo adaptors in the asymmetric coiled-coil structure of the dynein co-factor Bicaudal-D
    H. K. Salter, Y. Liu, A. N. Holding, C. Johnson, E. Stephens, J. Walshaw, S. L. Bullock
    The American Society For Cell Biology Annual Meeting, 2012, San Franciso, CA, USA.
  7. Resolving interactions involved in binding of the dynein co-factor Bicaudal-D (BicD) to Rab6
    Andrew N Holding, Elaine Stephens, Mark Skehel.
    EuPA/BSPR Prteomic Meeting, 2012, Glasgow, Scotland.
  8. Resolving interactions involved in binding of the dynein co-factor Bicaudal-D (BicD) to Rab6
    Andrew N Holding, Elaine Stephens.
    60th ASMS Conference on Mass Spectrometry and Allied Topics, 2012, Vancouver Convention Centre, Vancouver, BC, Canada.
  9. XL-SAXS and DNA replication
    Ana Toste Rêgo, Andrew Holding, Michal Hammel, Elaine Stephens, John Kuriyan and Meindert H. Lamers.
    Current Opinion in Structural Biology & DNA Repair, 2011, Amsterdam, The Netherlands
  10. Development of arginine and guanine specific isotopically-labelled linkers for the characterisation of binding interactions by mass spectrometry
    Andrew N Holding, Elaine Stephens.
    59th ASMS Conference on Mass Spectrometry and Allied Topics, 2011, Colorado Convention Center, Denver, CO, USA.
  11. Sdo1/Efl1 interaction site mapped by photocrosslinking
    Andrew N Holding, Nicholas Basse, Alan Warren, Elaine Stephens.
    Memorial symposium for Dr. Jonathan Spencer, 2010, University of Cambridge.
  12. Investigation into the mechanism of phenolic couplings during the biosynthesis of glycopeptide antibiotics
    Andrew N Holding, Jonathan B Spencer.
    Zing Conference in Natural Products, 2009, Antigua.

PhD thesis

Studies on the biosynthesis of non-ribosomal peptides

Abstract: The problem of bacterial resistance is of growing concern within the medical community. Eventually, even with responsible use of antibiotics, new compounds will be required to bypass the resistance that bacteria have acquired. Thus the expansion of knowledge and understanding of antibiotics is key in the development of new compounds in the fight against infection. One attractive starting point for the development of new compounds are those natural products generated by non-ribosomal peptide synthetases (NRPS), which include a range of clinically relevant glycopeptide antibiotics.

Several aspects of the biosynthesis of glycopeptide antibiotics were examined: first, the investigation to identify, by the use of directed evolution if 4-hydroxymandelic acid synthase (HmaS) from the gene cluster of the antibiotic chloroeremomycin may have evolved from its homologue 4-hydroxyphenylpyruvate dioxygenase (HppD). The summation of this work is published in FEBS Lett. 2006; 580:3445. Following on from this work was an investigation into the hypothesis that HmaS catalyses the turnover of the non-natural phenylpyruvic acid to produce a product with an inverted chiral centre compared to that of the natural substrate due to differences in substrate binding. Results showed that, while not the major product, the inverted product was detected via chiral GCMS. Secondly, it is shown that all three cytochrome P450 enzymes (OxyA-C) that catalyse the sequential formation of three essential oxidative cross-links within the chloroeremomycin molecule do so with the retention of the oxygen atom on the peptide backbone and without the incorporation of oxygen in the air. This portion of the work is published in ChemBioChem 2008; 9:2209. The final part of the study was the development of a high-throughput screening method for NRPS A-domains, with the aim of both rapid characterisation and directed evolution of novel substrate specificity. This led to the identification that the amino acid loaded by the first A-domain of the teicoplanin NRPS was shown to load the d-amino acid in preference to the l-amino acid. This is in contrast to the equivalent domain in the chloroeremomycin gene cluster that loads the l-amino acid.

Download: Studies on the biosynthesis of non-ribosomal peptides.