metabolomics, marine microbes, antibiotics, natural products, drug discovery

Endophytic microorganisms with potentially novel biosynthetic capabilities to produce new antibiotics have been obtained from underexplored areas, which experience environmental stress. Genomic and metabolomic tools will be employed to dereplicate microorganism in order to focus on those with novel chemistry and mechanism of action. The main objective of this project is to explore the production of new antimicrobials from actinomycetes (and/or fungal symbionts) and to pilot an efficient cultivation and production processes at a small scale whilst maintaining or enhancing synthesis of the targeted bioactive compounds. The strategic aim of the proposed application is to deliver to the student the training and experience to explore the genomic variation of microbes that can provide novel bioactive molecules through metabolomic tools. This would involve multivariate analysis of fused data from high-resolution nuclear magnetic resonance spectroscopy and mass spectrometry. The metabolomic profile will capture the relevant genetic material in systems that will allow characterizing the bioactive molecules in terms of their chemistry as well as biological effects. Large-scale production of target molecules will afford testing the potential value of promising molecules as leads for new antibiotics for human and animal health. The student will have the knowledge exchange opportunity to interact and get involved with biotechnology industries that work directly with the supervising team.

metabolomic tools involving multivariate analysis of nuclear magnetic resonance spectroscopic and mass spectrometric data, molecular biology/genomic studies.

[1]   Harvey, A.L.; Edrada-Ebel, R.; Quinn, R.J. The re-emergence of natural products for drug discovery in the genomics era. Nature reviews. Drug discovery 2015, 14, 111-129.

[2]  Macintyre, L.; Zhang, T.; Viegelmann, C.; Martinez, I.J.; Cheng, C.; Dowdells, C.; Abdelmohsen, U.R.; Gernert, C.; Hentschel, U.; Edrada-Ebel, R. Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts. Mar. Drugs 2014, 12, 3416-3448.

[3]   Viegelmann, C.; Margassery, L.M.; Kennedy, J.; Zhang, T.; O'Brien, C.; O'Gara, F.; Morrissey, J.P.; Dobson, A.D.W.; Edrada-Ebel, R. Metabolomic Profiling and Genomic Study of a Marine Sponge-Associated Streptomyces sp. Mar. Drugs 2014, 12, 3323-3351.

[4]   Cheng Cheng, Lynsey MacIntyre, Usama Ramadan Abdelmohsen, Hannes Horn, Paraskevi N. Polymenakou, RuAngelie Edrada-Ebel, Ute Hentschel. Biodiversity, anti-trypanosomal activity screening, and metabolomics profiling of actinomycetes isolated from Mediterranean sponges. PLOS ONE 2015 Sep 25;10(9):e0138528. doi: 10.1371/journal.pone.0138528

[5]  Kevin Purves, Lynsey MacIntyre, Debra Brennan, David H. Green, Ruangelie Edrada-Ebel, Katherine R. Duncan, Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting.  Metabolites. 2016 Jan 8;6(1). pii: E2. doi: 10.3390/metabo6010002.