Advances, Prospects & Challenges for MarineBiotechnology

Advances, Prospects & Challenges for MarineBiotechnology

Jan A.Jan A. OlafsenOlafsenUniversity of TromsUniversity of Tromsøø

DepartmentDepartment ofof MarineMarine BiotechnologyBiotechnologyemail: jan.olafsen@nfh.uit.noemail: jan.olafsen@nfh.uit.no

“ABIC 2008”Cork, Ireland, August 24-27, 2008

Marine Biotechnology?

Understand basic principles of marine life for: Responsible management of marine resources Social, market and trade development in the marine sector Improved quality of marine products (“healthy food”) Explore new opportunities for marine resources

The deciphering and use of marine biological systems- for industry, the benefit of society and protection of the marine environment

"He who commands the sea has command of everything” (Cicero)

“An Ocean of Opportunities?”Big or small - driven by curiosity - or what?

“What we try to do in science is to get ever closer to nature”"Both in space and time, we seem to be brought near to thatgreat fact — the mystery of mysteries — the first appearance ofnew beings on this earth” (Darwin)

"The most beautiful thing we can experience is the mysterious.It is the source of all true art and science” (Einstein)

The sectors of marine biotechnology- are multiple and diverse

MarineMarinebiotechnologybiotechnology

MarineMarinechemistrychemistry

Research toolsResearch tools

MarineMarinebiologybiology

MolecularMolecularbiology & geneticsbiology & genetics

EnvironmentalEnvironmentalissuesissues

AquacultureAquaculture

Fish processingFish processing FisheriesFisheries

Industry,Industry,Applications, IPRApplications, IPR

TechnologyTechnology

“Marine biotechnologies?”

Areas of Activity in MarineAreas of Activity in MarineBiotechnologyBiotechnology (US)(US)

PolysacchaPolysaccharidesrides Source for PharmaceuticalsSource for Pharmaceuticals NeurotoxinsNeurotoxinsMicrobialMicrobial sourcessources -- TheThe ArchaeaArchaea AquacultureAquaculture Research ProductsResearch Products

The promise of marine biotechnology?

An ocean of opportunities.....

....or a figment of imagination?

Blue biotech: The biotechnology without a market?- Small internal-market? (except aquaculture)

Blue biotech perceived as diverse

Not “technology driven” (imports technologies?)

StatusStatus of Marineof Marine BiotechnologyBiotechnology (US)(US)

Minimal commercial success compared toMinimal commercial success compared toterrestrial based biotechnologyterrestrial based biotechnology

Technologically,Technologically, ““the industry is poised onthe industry is poised onthe edge of a period of tremendousthe edge of a period of tremendouspotential ..potential ..”” (Colwell, 2002)(Colwell, 2002)

Lack of progress due to:Lack of progress due to: Difficulties of retrieving a sustained reliable harvest of marinDifficulties of retrieving a sustained reliable harvest of marinee

organismsorganisms Insufficient quantities of material to allow for study completioInsufficient quantities of material to allow for study completionn Difficulties culturing marine organisms in theDifficulties culturing marine organisms in the lablab

”Why Blue Biotech?”

... Do we have a choice?

Unique characteristics of marine life

BiodiversityBiodiversity

CommunicationCommunication andand signallingsignalling::•• nutrient aquisitionnutrient aquisition•• developmental biologydevelopmental biology•• hosthost interactionsinteractions•• defence reactionsdefence reactions

AdaptationAdaptation

Environmental factorsEnvironmental factors::•• temperaturetemperature•• pressurepressure•• salinitysalinity•• lightlightExtremophilesExtremophiles

- understanding, exploring and protecting life in the sea- a call for curiosity-driven research

InteractionsInteractionsSignallingSignalling

“application of modern molecular and genetic tools to the marine sciences”

Key elements of marinebiotechnology

• Adaptation to the environment (physical, chemical, biological)

• Signalling and communication

• Evolution, interaction and defense

• Natural substances for human benefit

• Environmental:

- Bioremediation and environmental biotechnology

- Biomass upgrading

• Food safety and traceability: Healthy and functional foods

Motivation!

Why marine biotechnology?

....the “selfish” viewpoint

• What is in it for me? Increase research grants?

• Highly relevant?

• Earn more money. Industrialize!

• Satisfy curiosity?

• Access to new/unique experimental models?

A EuropeanStrategy for

MarineBiotechnology

Tapping themolecular and

geneticpotential of themarine world?

***EuropeanScience

Foundation 2001

www.esf.org

To have a vision!... not only a strategy...

EurOcean 2004 Galway, Ireland“The Galway Declaration”

PRIORITIES FOR MARINE BIOTECHNOLOGY RESEARCH

Aquaculture

Transgenic fishBiomolecules

PharmaceuticalsEnvironmental

protection

Control ofhuman disease

MarineMarine BiodiversityBiodiversity((CC. Heip, Eurocean 2004. Heip, Eurocean 2004 GalwayGalway))

Red Clay at 3000 m depth

Pollution and bioremediation- a focus for marine biotechnology?

Bottom area sufferingsummer hypoxia, 1973

Bottom area sufferingsummer hypoxia, 1990

Applications

patentsStructural elucidationisolation / purification

Primary screeningcollection / taxonomy

DISCOVERY

toxicity / pharmacokineticformulation / stability

biological studiesPRECLINICAL

Dose / administration schememaximum tolerable dose

toxicity/pharmacokineticsPHASE I

Efficacy / safetySelection of therapeutic indication

PHASE II

Clinical comparison withstandard treatments

PHASE III

COMMERCIALISATION

collectionfermentationaquiculturesynthesis

secondaryscreening

ParmaMar Research & Development

ET-743

Aplidine

ThiocoralineLamellarinsVariolinsCrambescidins

TrunkamidesNeolaulilamideOthers

Kahalalide F

Isohomohalichondrins

Always have new products in the pipeline?

ES-285

Why search the marine environment?

Bioactives from terrestrial and marine bacteriaBioactives from terrestrial and marine bacteria

Novel antibiotics from marine sourcesExample: Antibacterial peptide from the spider crab

untreated treated

• Attacks the outersurface of bacteria(arrows)

• Kills bacteria withhigh specific activity

• Low toxicity tomammalian cells

• No resistencemechanisms known

Biotec Pharmacon Ltd., Norway(Courtesy of Dag. R. Gjellesvik and Jan Raa)

A relatively small company that originated from researchA relatively small company that originated from researchcarried out at the University of Tromscarried out at the University of Tromsøø onon immunostimulants.immunostimulants.Science driven.Science driven.

Create opportunities? Investment neededPush and Pull

Source: O. J. Marvik, Innovation Norway

Creativitypush

Marketpull

... what we could do

..also with marine models

Early bacterial colonization of fish larvae - A complex interaction

Bacteria in seawaterBacteria in seawater high diversityhigh diversity

opportunistic growthopportunistic growth

Microflora of marineMicroflora of marineinvertebrates andinvertebrates and

planktonplankton food organismsfood organisms

specific uptake?specific uptake? invertebrate innate defenceinvertebrate innate defence

moleculesmolecules

Interactions?Interactions?

Reservoir ofReservoir ofopportunistic pathogensopportunistic pathogens

Bacterial colonization of eggsBacterial colonization of eggs adhesion to egg chorionadhesion to egg chorion

high diversity and competitionhigh diversity and competition--protection?protection?

Ligands?

Bacterial uptake in larvaeBacterial uptake in larvae uptake of intact bacterial antigensuptake of intact bacterial antigens

immune priming?immune priming?

ReceptorsReceptors

Bacterial colonization of larvaeBacterial colonization of larvae host receptors?host receptors?

establishment of protective microflora?establishment of protective microflora?

Probiotics?

Symbiosis -advanced

interactions

Diversity - the driving force ofmarine ecosystems

...only the best-adapted species thrive in a given niche

A Fish Story

Gnotobiotic (germ-free) zebrafishreveal evolutionary conservedresponses to the gut microbiota

Rawls et al., PNAS 2004-1

• Intestinal epithelial cell proliferationstimulated:

• 212 genes regulated by the microbiota

• 59 responses conserved in the mouseintestine

Early colonization of the GI tract maybe responsible for changed metabolism inthe fish larvae

Love the One You’re with: Vertebrate Guts Shape Their MicrobiotaMargaret McFall-Ngai. Cell 2006, 127

Shaping of the Gut Microbiota by Its HostIn the microbiota of conventionally raised mice are introduced into the gut ofgerm-free zebrafish, and conversely, the microbiota of conventionally raisedzebrafish are transplanted into the gut of germ-free mice (Rawls et al., 2006)

Mice and zebrafish naturally have members of bacterial divisions in their gut indifferent proportions and as distinct phylotypes.

When the non-native consortium is introduced into one of these hosts, thehost animal appears to promote a higher proportion of the bacterial group thatis more abundant in its native consortium.

Bacterial modulation of intestinal glycan expressionA molecular foundation for commensalism - tailoring the (fucose-) receptor!

A gut microflora is required to initiate the developmentally regulated program offucosylated glycan production

Fucosylated glycans are induced in adult germ-free mice upon colonization with asingle member of the indigenous gut flora, Bacteroides thetaiotaomicron.

Invertebrate defense systems...primitive or sophisticated?

A great resource of bioactives

International cooperation

Develop open local,national, regional andinternational relations

Stimulate curiosity-drivenresearch on marine models

Invite communicationbetween differentscientific disciplinesl

Recruit theyoung

Marine Biotechnology Networks and Associations

• Need for an International Network?• Asian Pacific Society for Marine Biotechnology (APMBS)• European Society for Marine Biotechnology (ESMB)• Pan American Society for Marine Biotechnology (PAMBA)

”Borderless Biotech”?• A truly international, open network• Network of networks?

IMBA - International Marine Biotechnology Association•Promote research and education in marine biotechnology

- Improve teaching and post-doctoral training - increase mobility- Arrange meetings and workshops- Act as node for international cooperation

Marine Biotechnology Conferences

• International Conferences (IMBC´s)• 1989 Tokyo, Japan• 1991 Maryland, USA• 1994 Tromsø, Norway• 1997 Naples, Italy• 2000 Townsville, Australia• 2003 Tokyo, Japan• 2005 St. Johns, Canada• 2007 Eilat, Israel• 2010 China

• European Conferences and Workshops (ESMB-related)• 1992 Montpellier, France• 1996 UKMBC Edinburgh - Marine microbiology• 1997 Brest, France - Marine microorganisms for industry• 1998 Wilhelmshaven, Germany - Marine biotech applications• 1998 Wageningen, Netherlands - Bioengineering• 2001 Edinburgh, UK - Marine microbiology and biotechnol workshop• 2002 Nantes, France - Marine biotechnology for industry• 2002 Greifswald, Germany - Marine natural products• 2002 Wageningen, Netherlands - Bioenergy• 2003 Spain - Marine biotechnology engineering• 2004 Barcelona, Aquaculture Biotechnology (arranged by EAS)

Borderless BiotechNetwork of networks

Mediation and coordination between existingnetworks and organisations

Stimulate funding of new networksNo formal power - strength depends on the

strengths of the individual networks. Does not exclude membership by single

universities, hospitals, companies orpersons.

ScanBalt Campus - for education

MarEGene

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are needed to see this picture.

We´ll do it together!

Silicon Valley

The big fish –little fish model

Keep itKeep itsimplesimple

Basic researchModel systems

Networking& largeragendaInnovation

Science& technology

DemandMarket

Applications

Big science versus little scienceIn large networks or “centers of excellence” targeted research could make itdifficult for an individual scientist to do something original and creative.

Basicresearch

Biotechnologies:Biotechnologies: blueblue -- greengreen

Product and industrialdevelopments

Regionalcooperation

CrossCommunicationAgro-Marine)

BlueBiotech

”BorderlessBiotech”?

GreenBiotech

The biotechnologies - differences and synergism

SYNERGISM- Basic science- Methodology- Cross-cutting research- Health and energy- Aquaculture!

DIFFERENCES- Habitat - terrestrial versus marine...- Market and industry?- Funding and politics?- The academic platform - agro diverse and experienced

Future Common Challenges

- The role of biotechnology in feed, food and fuel production

- Systems biology for food, pharma and population genetics

- Roles and responsibilities of governments in promoting biotechinnovation: The Canadian experience

- Functional food research from an Industrial perspective

- HEALTHY FOOD (Marine oils)

- Enzyme evolution for development of third generation biofuels

- GeneticS for mitigating energy problems and global climate change

Marine stations

Research vessels

“Support for Marine Biotechnology Research”

Model systems

Institutions-laboratories

... Fulfilling the promise !

Creative scientists

A vision