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Hvorfor lete etter antibiotika i havet?

Bioingeniørdagen 2017

30.03.2017

Jeanette Hammer Andersen

Marin bioprospektering

Medisiner

Enzymer

Ingredienser

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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

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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