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Discovery of novel pharmaceuticals from marine and desert microorganisms


Project Description

Microorganisms from extreme environments such as the deep seas, cold seas and hyper arid deserts have been shown to produce a range of complex natural products with high biological activity. In this project you will investigate the chemistry of these compounds and their potential for treating a range of diseases. Via collaborations we obtain desert and marine samples from which you will isolate unique bacterial and fungal strains. Cultivating these under different conditions gives rise to varied metabolic profiles. We have new facilities for cultivating bacteria at very high pressures to mimic deep sea environments. You will use a range of chromatographic techniques to isolate the compounds from these cultured microbes. The next step will be to identify their chemical structures using spectroscopic techniques followed by testing the compounds in a range of biological assays to ascertain their biological activity and potential for use against human diseases.

As part of this project you will gain skills in microbiology, natural product chemistry and biological testing. You will work in a committed group of scientists interested in investigating natural resources for their potential to treat disease. The group is located in the Marine Biodiscovery Centre which houses state-of-the-art facilities and scientists with skills in microbiology, molecular biology, chemical analysis and natural product chemistry.

The pharmaceutical industry has identified a major gap in its portfolio. On the one hand, they are excellent at discovering small molecules that act via a lock and key type mechanism. On the other hand, some diseases are only treatable with biologics such as antibodies and proteins, with associated high costs and difficulties in administering them. The gap between these is filled by large cyclic molecules which behave like small molecule drugs in terms of administration, and behave like biologics in terms of therapeutic effects. However, pharmaceutical industry has no easy way to make such molecules in quantity, nor are there simple ways to modify them.

We have discovered a range of enzymes that allows us to make complex modified linear and cyclic peptides which have high biological activity in a number of human disease states. This process takes a few days, as compared to chemical synthesis which would take months or years.

In this project you will take a hybrid approach to the production of such compounds, using chemical synthesis together with enzymes to create a range of cyclic modified peptides for testing against a number of disease targets. You will gain skills in peptide synthesis, molecular biology, biochemistry and compound separation and identification.

You will work in a supportive group composed of molecular and cell biologists and synthetic and natural product chemists. The research environment for the biological and chemical parts of the project are world class. The biological work will be carried out at the Institute of Medical Sciences, and the chemical work will be carried out at the Marine Biodiscovery Centre.

Candidates should have (or expect to achieve) a UK honours degree at 2.1 or above (or equivalent) in Chemistry, biochemistry or pharmacy.

The successful applicant should have a background in Organic chemistry, Nuclear magnetic resonance spectroscopy and mass spectrometry.

APPLICATION PROCEDURE:

• Apply for Degree of Doctor of Philosophy in Chemistry
• State name of the lead supervisor as the Name of Proposed Supervisor
• State ‘Self-funded’ as Intended Source of Funding
• State the exact project title on the application form

When applying please ensure all required documents are attached:

• All degree certificates and transcripts (Undergraduate AND Postgraduate MSc-officially translated into English where necessary)
• Detailed CV
• Details of 2 academic referees

Informal inquiries can be made to Professor M Jaspars (@abdn.ac.uk) with a copy of your curriculum vitae and cover letter. All general enquiries should be directed to the Postgraduate Research School ()

Funding Notes

This project is advertised in relation to the research areas of the discipline of chemistry and microbiology. The successful applicant will be expected to provide the funding for Tuition fees, living expenses and maintenance. Details of the cost of study can be found by visiting View Website. THERE IS NO FUNDING ATTACHED TO THESE PROJECTS. Applicants should also be aware that Additional Research Costs of £6,000 per annum are required (above Tuition Fees and Living Expenses) for consumables.

References

1. “Dermacozines H-J Isolated from a Deep-Sea Strain of Dermacoccus abyssi from Mariana Trench Sediments” M. Wagner, W. M. Abdel-Mageed, R. Ebel, A. T. Bull, M. Goodfellow, H.-P. Fiedler and M. Jaspars, J Nat Prod, 2014, 77, 416-420.

2. “Chaxapeptin, a Lasso Peptide from Extremotolerant Streptomyces leeuwenhoekii Strain C58 from the Hyperarid Atacama Desert” Somayah S. Elsayed, Franziska Trusch, Hai Deng, Andrea Raab, Ivan Prokes, Kanungnid Busarakam, Juan A. Asenjo, Barbara A. Andrews, Pieter van West, Alan T. Bull, Michael Goodfellow, Yu Yi, Rainer Ebel, Marcel Jaspars, and Mostafa E. Rateb, J. Org. Chem. 2015, 80, 10252

3. “Antimicrobial Activity of Monoramnholipids Produced by Bacterial Strains Isolated from the Ross Sea (Antarctica)”, Pietro Tedesco, Isabel Maida, Fortunato Palma Esposito, Emiliana Tortorella, Karolina Subko, Chidinma Christiana Ezeofor, Ying Zhang, Jioji Tabudravu, Marcel Jaspars, Renato Fani and Donatella de Pascale, Marine Drugs, 2016, 14, 83

4. “Pseudochelin A, a siderophore of Pseudoalteromonas piscicida S2040” Eva C. Sonnenschein, Marc Stierhof, Stephan Goralczyk, Floriane M. Vabre, Leonie Pellissier, Kine Ostnes Hanssen, Mercedes de la Cruz, Caridad Diaz, Peter de Witte, Danielle Copmans, Jeanette Hammer Andersen, Espen Hansen, Venke Kristoffersen, Jose R. Tormo, Rainer Ebel, Bruce F Milne, Hai Deng, Lone Gram, Marcel Jaspars, Jioji N. Tabudravu, Tetrahedron, 2017, 73, 2633

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