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Contenido archivado el 2024-04-30

Marine Cyanobacteria as a source for Bioactive (apoptosis modifying) Compounds with potential as Cell Biology reagents and drugs

Objetivo



Background The present partners - representing European oell biologists, marine (micro)biologists, and chemists - will jointly search for more precise chemical tools (directed against specific enzymes) to control the oell signalling reactions leading to apoptotic (programmed) oell death. Apoptosis is presently one of the most intensely studied biological phenomena, both within basic and applied biosciences.
Specific objectives and expected advances
1 Sampling and growth of marine cyanobacteria from European coast-near seas and extreme polar regions. Sampling will be from coastal areas (Baltic sea, Iberian coast, Norwegian fjords), as well as from more extreme polar regions, including Spitsbergen and certain areas of the Antarctica. Monoculturing will be in sever specialised laboratories (Ia,Ib,IIa,III), large scale growth in two of them (Ia,III). It is expected to obtain enough biomass for initial screening (1lOOg) from a number of microbes, and to obtain kg amounts from at least some relevant cyanobacteria.
2 Extrachon, parhal purification and initial screening for bio-activity. Extracts (some partially purified) will be tested for ability to elicit or protect against apoptotic oell death of a number of normal and malignant oell types, for effects on the cytoskeleton, and for effects on isolated protein kinases and phosphatases known to affect cell function and viability. Such a systematic survey has not been done before, but extrapolation of data from preliminary screening of scattered samples indicate a huge potential for discovery of new activities.
3 Isolation, structure elucidation, and detailed probing of selected bio-active compounds. This will involve scale-up of the initial amount of relevant sample, and of extraction and initial purification procedures, followed by final purification and structure elucidation. The purified compounds will be thoroughly characterised with respect to action on cells and on isolated oell signalling enzymes (key kinases and phosphatases), and for degradation and metabolism.
4 Hemisynthetic modificahon of natural compounds (see above), and detailed probing of the effects of chemical modificahion on biological function and availability. This will serve to characterise the important functional groups of the natural compounds, but mostly to enhance their usefulness as cell biology tools or drug (increased bioavailability, potency, specificity). In the first phase hemisynthesis will be performed for nodularin and certain novel marine microcystins, which are already available in the network. 5 Publication, patenhng, commercialisahon. Scientifically important findings involving new compounds of general interest for cell biology research (modifiers of phosphorylation, cytoskeleton, apoptosis) will generally be sought published rapidly in high-ranking journals.
This will help to create a demand for the novel reagents, which will rapidly be exploited by the partners (notably the SME Ic/Va), with due caution for protection of rights, particularly for compounds with a market potential as medical drugs.

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Coordinador

UNIVERSITY OF BERGEN
Aportación de la UE
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Dirección
19,Aarstadveien 19
5019 BERGEN
Noruega

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Participantes (6)

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