Christina Spry

Contacts

Contact email:christina.spry@anu.edu.au
Contact phone:+61 2 6125 6229 (Office)
Location:Rm 2.018, Level 2, Linnaeus Building (134)
Centre:Division of Biomedical Science and Biochemistry
Link:ANU Researchers profile

Group membership

Group Leader, Spry Group - Drug discovery for infectious diseases

Christina Spry completed a Bachelor of Science with Honours degree at the Australian National University.  She continued at the Australian National University for her graduate studies and in 2009 was awarded a PhD for her work with A/Prof Kevin Saliba investigating and targeting the metabolism of vitamin B5 by the human malaria parasite.

After her PhD, Christina worked as a Post-doctoral Fellow with A/Prof Saliba and Prof Kiaran Kirk, before being awarded an NHMRC Overseas-based Early Career Fellowship, which, in 2011, took her to the University of Cambridge, UK, to work with Prof Chris Abell.  In Cambridge Christina applied fragment-based approaches to the discovery of inhibitors of vitamin B5 metabolism in bacteria including Mycobacterium tuberculosis – the causative agent of tuberculosis.

At the end of 2015 Christina returned to the Research School of Biology at the Australian National University where she is based in the Saliba lab and continuing her NHMRC Early Career Fellowship.

Research interests

Christina has a keen interest in antimicrobial drug discovery.  To this end her research is focused on understanding how microbes utilise essential nutrients and in identifying novel inhibitors of these processes that thereby possess antimicrobial activity.  To date her research has primarily focused on understanding and exploiting for drug discovery the pathway by which pantothenate (vitamin B5) is metabolised to the fundamental enzyme cofactor coenzyme A.  Her research has both a malaria and tuberculosis focus and involves cell culture, heterologous protein expression and chemical and biophysical techniques as core methodologies.  Building upon her experiences working with Prof Chris Abell at the University of Cambridge, Christina is using fragment-based approaches to drug discovery as an alternative to high-throughput screening in her research.

  • Bakali, J, Blaszczyk, M, Evans, J et al. 2023, 'Chemical Validation of Mycobacterium tuberculosis Phosphopantetheine Adenylyltransferase Using Fragment Linking and CRISPR Interference', Angewandte Chemie International Edition, vol. 62, no. 17.
  • Howieson, V, Zeng, J, Kloehn, J et al. 2023, 'Pantothenate biosynthesis in Toxoplasma gondii tachyzoites is not a drug target', International Journal for Parasitology: Drugs and Drug Resistance, vol. 22, pp. 1-8.
  • Hayward, J, Makota, F, Cihalova, D et al. 2023, 'A screen of drug-like molecules identifies chemically diverse electron transport chain inhibitors in apicomplexan parasites', PLoS Pathogens, vol. 19, no. 7.
  • Guan, J, Spry, C, Tjhin, E et al. 2021, 'Exploring Heteroaromatic Rings as a Replacement for the Labile Amide of Antiplasmodial Pantothenamides', Journal of Medicinal Chemistry, vol. 64, pp. 4478-4497.
  • Evans, J, Murugesan, D, Post, J et al. 2021, 'Targeting Mycobacterium tuberculosis CoaBC through Chemical Inhibition of 4'-Phosphopantothenoyl-l-cysteine Synthetase (CoaB) Activity', ACS Infectious Diseases, vol. 7, no. 6, pp. 1666-1679.
  • Mendes, V, Green, S, Evans, J et al. 2021, 'Inhibiting Mycobacterium tuberculosis CoaBC by
    targeting an allosteric site', Nature Communications, vol. 12.
  • Tjhin, E, Howieson, V, Spry, C et al. 2021, 'A novel heteromeric pantothenate kinase complex in apicomplexan parasites', PLoS Pathogens, vol. 17, no. 7.
  • Spry, C, Barnard, L, Kok, M et al. 2020, 'Toward a Stable and Potent Coenzyme A-Targeting Antiplasmodial Agent: Structure-Activity Relationship Studies of N-Phenethyl-α-methyl-pantothenamide', ACS Infectious Diseases, vol. 6, no. 7, pp. 1844-1854.
  • Spry, C & Coyne, A 2019, 'The Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases', in Venkatesan Jayaprakash, Daniele Castognolo, Yusuf Ozkay (ed.), Medicinal Chemistry of Neglected and Tropical Diseases: Advances in the Design and Synthesis of Antimicrobial Agents, CRC Press - Taylor & Francis Group, United States of America, pp. 18-47.
  • Chan, D, Hess, J, Shaw, E et al. 2019, 'Structural insights into Escherichia coli phosphopantothenoylcysteine synthetase by native ion mobility-mass spectrometry', Biochemical Journal, vol. 476, no. 0264-6021, pp. 3125 - 3139.
  • Spry, C, Sewell, A, Hering, Y et al 2018, 'Structure-activity analysis of CJ-15,801 analogues that interact with Plasmodium falciparum pantothenate kinase and inhibit parasite proliferation', European Journal of Medicinal Chemistry, vol. 143, pp. 1139-1147.
  • Tjhin, E, Spry, C, Sewell, A et al 2018, 'Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues', PLoS Pathogens, vol. 14, no. 4, pp. 1-30.
  • Guan, J, Tjhin, E, Howieson, V et al 2018, 'Structure-Activity Relationships of Antiplasmodial Pantothenamide Analogues Reveal a New Way by Which Triazoles Mimic Amide Bonds', ChemMedChem, vol. 13, no. 24, pp. 2677-2683pp.
  • de Villiers, M, Spry, C, Macuamule, C et al 2017, 'Antiplasmodial Mode of Action of Pantothenamides: Pantothenate Kinase Serves as a Metabolic Activator Not as a Target', ACS Infectious Diseases, vol. 3, no. 7, pp. 527-541.
  • Scott, D, Spry, C & Abell, C 2016, 'Differential Scanning Fluorimetry as Part of a Biophysical Screening Cascade', in D. A. Erlanson and W. Jahnke (ed.), Fragment-based Drug Discovery: Lessons and Outlook, Wiley-VCH Verlag GmbH & Co. KGaA., Weinhem, Germany, pp. 139-172.
  • Spry, C & Coyne, A 2015, 'Fragment-Based Discovery of Antibacterials', in Steven Howard and Chris Abell (ed.), Fragment-Based Drug Discovery, Royal Society of Chemistry, Camridge, United Kingdom, pp. 177-196.
  • Saliba, K & Spry, C 2015, 'Coenzyme A Biosynthesis', in Marcel Hommel & Peter Kremsner (ed.), Encyclopedia of Malaria, Springer New York, Online, pp. 1-11pp.
  • Spry, C, Saliba, K & Strauss, E 2014, 'A miniaturized assay for measuring small molecule phosphorylation in the presence of complex matrices', Analytical Biochemistry, vol. 451, pp. 76-78.
  • Saliba, K & Spry, C 2014, 'Exploiting the coenzyme A biosynthesis pathway for the identification of new antimalarial agents: The case for pantothenamides', Biochemical Society Transactions, vol. 42, no. 4, pp. 1087-1093.
  • Spry, C, Macuamule, C, Lin, Z et al 2013, 'Pantothenamides Are Potent, On-Target Inhibitors of Plasmodium falciparum Growth When Serum Pantetheinase Is Inactivated', PLOS ONE (Public Library of Science), vol. 8, no. 2, pp. 1-12.
  • de Villiers, M, Macuamule, C, Spry, C et al. 2013, 'Structural modification of pantothenamides counteracts degradation by pantetheinase and improves antiplasmodial activity', ACS Medicinal Chemistry Letters, vol. 4, no. 8, pp. 784-789.
  • Spry, C, Van Schalkwyk, D, Strauss, E et al 2010, 'Pantothenate Utilization by Plasmodium as a Target for Antimalarial Chemotherapy', Infectious Disorders - Drug Targets, vol. 10, no. 3, pp. 200-216.
  • Spry, C & Saliba, K 2009, 'The Human Malaria Parasite Plasmodium falciparum Is Not Dependent on Host Coenzyme A Biosynthesis', Journal of Biological Chemistry, vol. 284, no. 37, pp. 24904-24913.
  • Spry, C, Kirk, K & Saliba, K 2008, 'Coenzyme A biosynthesis: an antimicrobial drug target', FEMS Microbiology Reviews, vol. 32, pp. 56-106.
  • Lehane, A, Marchetti, R, Spry, C et al 2007, 'Feedback Inhibition of Pantothenate Kinase Regulates Pantothenol Uptake by the Malaria Parasite', Journal of Biological Chemistry, vol. 282, no. 35, pp. 25395-25405.
  • Spry, C, Chai, C, Kirk, K et al 2005, 'A Class of Pantothenic Acid Analogs Inhibits Plasmodium falciparum Pantothenate Kinase and Represses the Proliferation of Malaria Parasites', Antimicrobial Agents and Chemotherapy, vol. 49, no. 11, pp. 4649-4657.

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