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BIOTEK2021-Bioteknologi for verdiskaping
Cell-based screening for small membrane permeable metal chelators of marine origin
Awarded: NOK 5.4 mill.
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Project Number:
208463
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Project Period:
2011 - 2017
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Several human diseases involve iron dyshomeostasis, and metal accumulation of iron, copper, cadmium, mercury and lead in human organs affect our well-being, cause cancer and accelerate ageing of organs. Low-toxic compounds capable of removing potentially toxic metals from cells and tissue are therefore sought. Marine organisms have developed sophisticated systems for the acquisition, storage and utilization of a variety of metals toxic for humans. This makes them excellent targets for screening of metal c helators. Recently, we developed the Cellular Lipid Peroxidation Antioxidant Activity (CLPAA) assay found suitable for identifying membrane permeable iron chelators. In addition to using CLPAA, a major goal of this application is to develop cellular assay s for screening of membrane permeable chelators specific also for other metals such as copper, cadmium, mercury and lead related to human pathologies. Development of new cellular medium- and high throughput screening (HTS) assays to investigate removal (' wash out') of toxic or excess metals from cells will include method developing attempts using metal specific intracellular fluorescent probes and the Scintillation Proximity Assay (SPA). As a follow-up assay we have already set up the Comet assay, where p rotective effects by chelators from metal-catalyzed DNA damage by reactive oxygen species (ROS; e.g. H2O2) can be studied. Screening is performed on semi-purified (Flash or HPLC chromatography) fractionated extracts from several types of marine organisms. Extracts giving active 'hits' in assays are further purified to obtain pure compounds which are characterized for chemical structure etc, using mass spectrometry and NMR techniques. For larger quantities, compounds are either extracted or synthesized and retested in assays with comparison of known commercially available compounds. Developed drugs are intended for treatment of human diseases and detoxifications related to excess maliciously placed metals.
Funding scheme:
BIOTEK2021-Bioteknologi for verdiskaping
2.0BILL. NOKtotal funding in the programme period322PROJECTShave received funding in the programme period5SOURCEShave financed the programme
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NordområdeneKlima, miljø og biologiske ressurserMarinPolitikk- og forvaltningsområderBioteknologiLTP3 Hav og kystGrunnforskningLTP3 Styrket konkurransekraft og innovasjonsevneNordområdeneUnike forskningsmuligheterMarinØkosystem (utgår 2014)LTP3 Nano-, bioteknologi og teknologikonvergensBransjer og næringerHelsenæringenPortefølje Banebrytende forskningPortefølje ForskningssystemetBransjer og næringerDelportefølje Et velfungerende forskningssystemDelportefølje KvalitetLTP3 Marine bioressurser og havforvaltningNordområdeneKunnskapsbasert næringsutviklingInnovasjon i offentlig sektor (utgår 2014)Innovasjoner i virksomheter innenfor offentlig forvaltning og tjenesteytingPolitikk- og forvaltningsområderNæring og handelPolitikk- og forvaltningsområderHelse og omsorgPortefølje HelsePortefølje InnovasjonLTP3 HelseLTP3 Et kunnskapsintensivt næringsliv i hele landetLTP3 Høy kvalitet og tilgjengelighetInnovasjon i offentlig sektor (utgår 2014)LTP3 Muliggjørende og industrielle teknologierHelsePortefølje Muliggjørende teknologierHelseBasal biomedisinsk forskningAnvendt forskningNordområdenePolitikk- og forvaltningsområderLæring, skole og utdanningLTP3 Fagmiljøer og talenter