Postgraduate research opportunities

Metabolomics-guided study of antibiotic compounds from marine microbial symbionts and terrestrial endophytes

Secondary metabolomics; marine natural products; antibiotics; anti-cancer drugs; NMR; MS; drug discovery; multivariate analysis

Number of places

1

Opens

14 February 2020

Deadline

31 July 2020

Duration

36 Months

Eligibility

Master degree in Chemistry or Microbiology or Biotechnology

Project Details

Large numbers of compounds with new structures and various bioactivities have been isolated from microbial sources particularly from marine microbial symbionts and terrestrial endophytes. Endophytes are organisms, often fungi and bacteria that live between living plant cells. The relationship established with the macro-organism is symbiotic without causing a disease to the host. Metabolomics data analysis will be used to aid strain selection by chemical profiling a variety of species by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography high-resolution mass spectrometry (LC-HRMS). Dereplication will be performed through an in-house Excel Macro by coupling the LC-HRMS data with the Dictionary of Natural Products (DNP) database. Multivariate analysis using SIMCA and other statistical platforms will be employed to define the uniqueness in the chemical profile of the microbial isolate which could be indicated as outliers. Finally, H1 NMR data and bioactivity data (e.g. anti-biofilms, anti-cancer) will indicate the presence of interesting compounds. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and other statistical tools will used to predict the bioactive metabolites for further isolation work.

Project aim

  • To create a metabolomics-bioassay guided approach as an optimisation tool for the scale-up of a bioactive fungal endophyte
  • To employ a metabolomics-guided approach to pinpoint the biologically active compounds against biofilm formation in multi-resistant bacteria as well as other biological activities.

Techniques used:

  • Various types of media will be used for the scaling-up. Thus, media optimisation will be done. The medium that will afford better yield, most diverse chemistry, and potent biological activity will be chosen for scaling-up.
  • Multivariate analysis will be used to guide the prediction and interpretation of data. A metabolomics-bioassay guided approach will be created for each of the scaled-up endophytes to pinpoint the biologically active compounds.
  • High-throughput fractionation will be accomplished to pinpoint and validate the bioactive compounds.
  • Nuclear magnetic resonance (NMR) and high-resolution mass spectroscopy (LC-HRMS) will be implemented to identify the bioactive compounds.
  • Fractions will be tested against biofilm from multi-resistant Staphylococcus aureus and cell lines in 96-well microplates using fluorescence-based assays.

Funding Details

Applicant will need to self-fund, find sponsorship for tuition and bench fees of £10,000 per annum for duration of studies

Supervisor

Primary Supervisor: RuAngelie Edrada-Ebel

Email: ruangelie.edrada-ebel@strath.ac.uk

Further information

Kevin Andrew Stuart, Keira Welsh, Molly Clare Walker & RuAngelie Edrada-Ebel (2020) Metabolomic tools used in marine natural product drug discovery, Expert Opinion on Drug Discovery, DOI: 10.1080/17460441.2020.1722636

Sebak M, Saafan AE, AbdelGhani S, Bakeer W, El-Gendy AO, Espriu LC, Duncan K, Edrada-Ebel R (2019) Bioassay- and metabolomics-guided screening of bioactive soil actinomycetes from the ancient city of Ihnasia, Egypt. PLoS One 14 (12):e0226959. doi:10.1371/journal.pone.0226959

Raheem DJ, Tawfike AF, Abdelmohsen UR, Edrada-Ebel R, Fitzsimmons-Thoss V (2019) Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta). Sci Rep 9 (1):2547. doi:10.1038/s41598-019-38940-w

Tawfike AF, Tate R, Abbott G, Young L, Viegelmann C, Schumacher M, Diederich M, Edrada-Ebel R (2017) Metabolomic Tools to Assess the Chemistry and Bioactivity of Endophytic Aspergillus Strain. Chem Biodivers 14 (10). doi:10.1002/cbdv.201700040

Harvey AL, Edrada-Ebel R, Quinn RJ (2015) The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 14 (2):111-129. doi:10.1038/nrd4510

Contact us

Primary Supervisor: RuAngelie Edrada-Ebel

Email: ruangelie.edrada-ebel@strath.ac.uk