2005 IRISH SCIENTIST YEAR BOOK

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Cork Institute of Technology
Ambrose Furey
Drugs from the sea: marine bio-prospecting

The ocean is the richest source of chemical diversity in our world, it covers 70% of the earth's surface and hosts in excess of 300,000 described species of plants and animals, as well as very large numbers of microbial species, including bacteria, micro algae and fungi. Since the 1990's, several marine species have been used as a source of unique bioactive compounds, which have been exploited for the development of a range of drug products.

A case in point is the drug Cytarabine, used for the treatment of a range of lymphomas and leukaemias, which was developed following the isolation of C-nucleocides from the Caribbean sponge, Cryptotheca [1]. One of the most successful anti-cancer agents effective against melanoma and ovarian cancer, Bryostatin 1, is derived from the marine bryozoan, Bugula Neritina [2]. Luffariella variabilis , the Palauan sponge, secretes a substance called sesterterpene manolid, which has been demonstrated to exert a powerful anti-inflammatory and analgesic effect in humans; its mode of action is as a synovial PLA 2 inhibitor; PLA 2 is involved in the pathogenis of many inflammatory diseases in humans [3].


Dr Kevin J. James (Director of PROTEOBIO) explaining the technique of nanoliquid chromatography-tandem quadrupole time-of-flight mass spectrometry (QqTOF) to Ms. Una Cuffe, PhD researcher funded by Irish Research Council for Science, Engineering and Technology (IRCSET).

PROTEOBIO, the Mass Spectrometry Centre for Biotoxin and Proteomics Research, has the unique distinction within Ireland of isolating and structurally elucidating a range of new bioactive compounds from the marine environment. PROTEOBIO research centre comprises 20 research scientists, 50% of whom are international; to date 25 PhD projects have been undertaken. The research centre located in the Department of Chemistry, CIT, possesses state-of-the-art chromatography and nano technology facilities together with complimentary mass spectrometry technologies, which enables very sensitive and selective structural investigations to be conducted. Dr Kevin J James, Director of PROTEOBIO, and Dr Ambrose Furey, Manager, have established a collaborative link with marine researchers in Chile with the objective of collecting symbionts of higher marine phyla from the coastline of Chile and culturing them in the laboratory. To date, more than 2000 strains of bacteria have been successfully grown as monocultures in the laboratory.


Dr Ambrose Furey (Manager of PROTEOBIO) carrying out method development on a liquidchromatography system coupled to a ThermoFinnigan MAT LCQ ion-trap mass spectrometer.

Preliminary studies have indicated that extracts taken from selected bacteria display potent bioactivity against a number of protozoan pathogens, including Chaga's disease, malaria, and amoebic dysentery, whilst not compromising the integrity of human cell lines. PROTEOBIO will isolate, purify and structurally characterise, using LC-MS/MS, the bioactive agents from these bacterial extracts, which may then be developed as drug candidates.

PROTEOBIO is responding to an economic and strategic shift in emphasis in Ireland from the production of bulk pharmaceuticals to the discovery and development of new drugs. This shift has been in an area that is driven and supported by the IDA and is one of the targets set for Ireland under the National Development Plan and is a key area driven by IDA policy. Such developments provide employment opportunities for science graduates and will expand Ireland's position in the bio-pharma sector.

Ireland has always had a humanitarian role in international affairs. The discovery and isolation by PROTEOBIO of bacterial derived anti-protozoan agents, that may potentially combat diseases that afflict the developing world, will continue an altruistic tradition that the Irish are renowned for worldwide. In the long term, it is anticipated that this project may lead to the utilisation and development of Ireland's marine natural resources, not previously exploited.


References

1. The Lancet, Oncology Vol 2 April 2001.

2. Med Res Rev 1999; 19:388-407. Wender P.A., et al. The rational design of potential chemotherapeutic agents: the synthesis of byrostatin analogues.

3. Garcia-Pastor, P., et al. (1999) Modulation of acute and chronic inflammatory processes by cacospongionolide B, a novel inhibitor of human synovial phospholipase A 2 , Br. J. Pharmacol. 126, 301-311].

Contact: Dr Kevin J. James (Director);
Dr Ambrose Furey (Manager),
PROTEOBIO (Mass Spectrometry Centre for Biotoxin and Proteomics Research),
Department of Chemistry, Cork Institute of Technology, Bishopstown, Cork.
Tel: 021-4326701; Fax: 021-4345191;
E-mail: [email protected] / [email protected]