Antimicrobial Metabolomics Research Group

Martin Scanlon

Dr Darren Creek


NHMRC RD Wright Career Development Fellow

Drug Delivery, Disposition and Dynamics
Monash Institute of Pharmaceutical Sciences
Monash University, Parkville campus
381 Royal Parade, Parkville, Vic, 3052
Room 2.2.233
Phone: +61 (0) 3 9903 9249
Fax: +61 (0) 3 9903 9583
darren.creek@monash.edu
www.creek-lab.com

Biosketch

Darren completed his PhD in pharmaceutics at MIPS with Profs Sue and Bill Charman studying the mechanisms of action and clearance for novel antimalarial drugs, leading to the discovery of OZ439, a potent and long-acting antimalarial currently in clinical trials. Darren then obtained first-hand experience  of  tropical disease research, working in a clinical trial for antimalarials in rural Uganda. Dr Creek has post-doctoral experience in pre-clinical drug discovery at the Centre for Drug Candidate Optimisation, Monash University, and in parasite biochemistry at the Wellcome Centre for Molecular Parasitology  at  the University of Glasgow. During his CJ Martin fellowship at the University of Glasgow, Darren played a major role in the implementation of the Scottish Metabolomics Facility and developed novel analytical methods for metabolomics, including the widely-used metabolomics software, IDEOM. He was  recently  elected to the board of directors for the international Metabolomics Society.

Darren recently moved to MIPS to start a new laboratory with a focus on development and application of novel metabolomics techniques for parasitology and pharmacology. His work has recently provided new insights into protozoan parasite metabolism, in vitro culture medium development and mechanisms  of  action and resistance for drugs against malaria and trypanosomiasis.

Project Areas

student in lab

The Creek laboratory uses advanced metabolomics and systems pharmacology methods to investigate drug action in microbial pathogens.

"Improving our understanding of metabolism in bacterial and parasitic pathogens will facilitate the discovery of new medicines that are urgently needed for the treatment of infectious diseases across the globe."

Our laboratory is at the forefront of the development and application of metabolomics technology. The high resolution mass spectrometry capabilities allow us to investigate the impact of drugs on metabolites, lipids and proteins in a holistic, system-wide manner. This modern approach, combined with  established  biochemical techniques, allows us to investigate molecular mechanisms of microbial growth and drug action on an unprecedented scale.

Current projects focus on understanding the mechanisms of action, toxicity and resistance for drugs to treat Human African Trypanosomiasis (Trypanosoma brucei ), Malaria (Plasmodium falciparum) and Gram negative superbugs (Acinetobacter baumannii and Klebsiella pneumoniae). Each of these pathogens cause extensive mortality and pose significant threats to global health due to  increasing  resistance to currently-available antimicrobials. Additional projects in the lab aim to further investigate the connectivity and regulation of metabolic pathways for these pathogens, with the hope of identifying new drug targets.

Key Publications: (http://scholar.google.com/citations?user=JXDhpZsAAAAJ&hl=en)

Chokkathukalam A, Kim DH, Barrett MP, Breitling R and Creek DJ: Stable isotope-labeling studies in metabolomics: new insights into structure and dynamics of metabolic networks. Bioanalysis 2014; 6 (4), 511-524

Creek DJ and Barrett MP: Determination of antiprotozoal drug mechanisms by metabolomics approaches. Parasitology 2014; 141 (1), 83-92

Oppenheim RD, Creek DJ, Macrae JI, Modrzynska KK, Pino P, et al. BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei. PLoS Pathogens 2014; 10(7): e1004263.

Trochine A, Creek DJ, Faral-Tello P, Barrett MP and Robello C: Benznidazole Biotransformation and Multiple Targets in Trypanosoma cruzi Revealed by Metabolomics. PLoS neglected tropical diseases 2014; 8 (5), e2844

Creek DJ, Nijagal B, Kim D-H, Rojas F, Matthews KR and Barrett MP: Metabolomics guides rational development of a simplified cell culture medium for drug screening against Trypanosoma brucei. Antimicrobial Agents and Chemotherapy 2013; 57 (6): 2768-2779

Ali, JAM, Creek, DJ, Burgess, K, Allison, HC, Field, MC, Maser, P and De Koning, HP. Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines. Molecular Pharmacology 2013; 83 (2): 439-453.

Creek, DJ, Chokkathukalam, A, Jankevics, A, Burgess, KEV, Breitling, R and Barrett, MP. Stable isotope-assisted metabolomics for network-wide metabolic pathway elucidation. Analytical Chemistry 2012; 84 (20): 8442–8447

Creek, DJ, Jankevics, A, Burgess, KEV, Breitling, R and Barrett, MP. IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data. Bioinformatics 2012; 28 (7): 1048-9  (http://mzmatch.sourceforge.net/ideom.php)

Vincent, IM, Creek, DJ, Burgess, K, Woods, DJ, Burchmore, RJS and Barrett, MP. Untargeted metabolomics reveals a lack of synergy between nifurtimox and eflornithine against Trypanosoma brucei. PLoS Neglected Tropical Diseases 2012; 6 (5): e1618.

Creek, DJ, Jankevics, A, Breitling, R, Watson, DG, Barrett, MP and Burgess, KEV. Toward global metabolomics analysis with hydrophilic interaction liquid chromatography-mass spectrometry: improved metabolite identification by retention time prediction. Analytical Chemistry 2011; 83 (22): 8703-10

Charman, SA, Arbe-Barnes, S, Bathurst, IC, et al., Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proceedings of the National Academy of Sciences. 2011; 108 (11): 4400-5

Current Major Funding

2015-2018: NHMRC RD Wright Biomedical Career Development Fellowship #APP1088855: D Creek $412,000 "Systems pharmacology of antimicrobial drugs"

2015-2017: NHMRC Project Grant #APP1087735: D Creek $470,000 "Discovery of active metabolic pathways suitable for drug targeting in Trypanosoma brucei"

2015-2017: NHMRC Project Grant #APP1079351: J Baell, V Avery, S Charman, D Creek & M Piggott $510,000 "Discovery of single agents to treat Chagas disease and human African trypanosomiasis"

2014-2019: NIH R01: J Li, J Song, D Creek, T Velkov, T Purcell & P Hertzog  $4.85 million    "New Tricks for 'Old' Drugs: PK/PD of Polymyxin Nonantibiotic Combinations"

Current lab members:

Carlo Giannangelo, PhD student
Anna Sexton, Research Assistant
Daniel Stoessel, Visiting Student
Katherine Ellis, Honours Student


Major Collaborating Labs: Prof Susan Charman, Prof Jian Li, Prof Jonathan Baell, Dr Martin Scanlon, Dr Erica Sloan, Dr Natalie Trevaskis, Prof Christian Doerig, A/Prof Jose Garcia Bustos , A/Prof Bayden Wood.