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Hvorfor lete etter antibiotika i havet?
Bioingeniørdagen 2017
30.03.2017
Jeanette Hammer Andersen
Marin bioprospektering
Medisiner
Enzymer
Ingredienser
2
Natural products in drug discovery
Small molecule approved drugs 1981-2014 (n=1211)
S ND S/NM S*/NM N S* NB S Synthetic drug
ND Natural product derivative
S/NM Mimic of natural product
S* Synthetic drug (natural product pharmacophore)
N Unaltered natural product
NB Botanical drug (defined mixture)Newman & Cragg, J. Nat. Prod. 79, 2016
Natural products in drug discovery
35 %
65 %
Natural products* versus Synthetic compounds
S NP*
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Legemidler fra havet
Yondelis®
Bløtvevskreft
Halaven®
Brystkreft
Ecteinascidia turbinata
inaturalist.orgHalichondria okadai
www.chm.bris.ac.uk-
Prialt ®
Smertelindring
Conus magus
Tromsø
Sampling area> 1000 stations
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Marine organismer
Invertebrater Mikroorganismer
Marine organismer i laben:
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Marbio areas of interest
Marine invertebrates
Marine microorganisms
• Anticancer
• Antioxidants
• Immunomod.
• Antibacterial
• Diabetes
Novel chemistry
Antibacterial assays
• Growth inhibition:
– E.coli
– P.aeruginosa
– E. faecalis
– S.aureus
– MRSA
• Inhibition of biofilm
formation
– S.epidermidis
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Marine
Ekstrakter
Kjemisk
opprensing
Biologisk screening
Identifisering
Aktive stoffer
Arbeidsflyt
Marine mikro-
organismer
Genteknologi
12
Marine fungi in Marbio (2015-)
Isolates Fermentations
Extracts/fractions
• Priorization• Scale-up• Isolation
Plug-assay
Bioassays
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Antibakteriell effekt av marine sopp økes ved
ko-kultivering
Fungal extracts that showed antibacterial activity (50 μg/mL.) Activity is expressed as optical density (OD) measured at 600 nm.
Vertical axis labels show isolate ID – fraction ID – bacterium tested against:
GBS=Group B Streptococcus
E.F= Enterococcus faecalis
Digibiotics – new projects
• Digital discovery of antimicrobial molecules with
reduced risk of resistance from marine Arctic
resources (funded by NFR, DLN)
• AntibioSpec (funded by UiT)
Marine
microorganismsFermentation Extraction/
fractionationBioassays
Sequencing/Genome
scanning
Isolation/
Identification
Bioactive compounds
Marbio
Workpackage 1:
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Bioktivitets-screening(1/2nd)
3rd screening
Identification Isolering
mg of compound
Strukturoppklaring
Fractionation
No bioactivityKnowncompound/knownbioactivity
Low amount ofcompound Known compound
Hit
Bioprospecting workflow:
Discovery Preclinical lead Phase I Phase II Phase II Market
Phases of drug development:
Brystkreft celler Normale lunge fibroblaster
• Selektiv mot kreftceller
• Target i cellene er identifisert
• Optimalisering pågår
Ny kjemi i en «slektning» av brennmaneten
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Marbio biodiscovery pipeline
Hvorfor lete i havet
• Uutforskede marine ressurser
• Kjemisk diversitet er mye større enn i syntetiske bibliotek
• Genteknologi-øker mulighetene (syntetisk biologi)
• Biologisk diversitet = kjemisk diversitet
N
NHN
O
HN
N
N
N
NN
HN
O
O
NHCH3
H3OC
OH OO
OHO
OO
OO
NHO O
OH
O
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Brennpunkt 15.03.2016
Marbio 2017• Jeanette Hammer Andersen (Prof.)
• Espen Hansen (Senior researcher)
• Kine Østnes Hanssen (Postdoc)
• Teppo Rämä (Postdoc)
• Kirsti Helland (technician)
• Chun Li (technician)
• Marte Albrigtsen (technician)
• Venke Kristoffersen (PhD stud)
• Priyanka Michael (PhD stud)
• Richard Ingebrigsten (PhD stud)
• Renate Døvig Osvik (PhD stud)
• Ole Christian Hagestad (PhD stud)
• MARPIPE (ITN) PHD
• AntiBioSpec PHD
• Hanne Bragmo (MSc stud)
• Eirin Glomsaker (MSc stud)
• Marte Jenssen (MSc stud)
More than 30 national/international collaborators
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www.cnn.com/vitalsignshttps://www.youtube.com/watch?v=17BTdo
VOI1A&feature=youtu.be