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From the SEA to the SOLution. An integrative assessment of marine pollution in a changing Arctic

Marine chemical pollution poses known threats to human health and to biodiversity, ecosystem and societal services. The Arctic is a major sink of global mercury (Hg) pollution. Arctic sediments, sea and glacial ice constitute vast Hg reservoirs. Recent studies raise concerns about their increasing role as local Hg sources. In a rapidly warming Arctic, the consequences of potentially increased environmental Hg on marine biota remain unknown. The objective of SEASOL is to identify the pathway(s) of Hg bioaccumulation in marine food webs of the High Arctic Kongsfjorden (Svalbard). This changing glacial fjord is recognised as a ‘natural laboratory’ of climate change in the Arctic. The fellow’s earlier research has shown the sole measurement of Hg levels as insufficient to connect biotic Hg dynamics to environmental change, whereas the analysis of Hg stable isotopes proved to be a promising tool for source discrimination and biotic transfer. SEASOL will build on the novel application of stable isotope analysis to identify the sources of Hg within the fjord system and the pathways to Hg accumulation within sentinel marine species. On the short-term, the study will provide fundamental knowledge to help understand how emerging sources of Hg from rapid environmental change will impact Arctic marine predators. On the long-term, SEASOL will contribute to the development of early-warning, adaptive management strategies, including modelling, for mitigating the cumulative impact of pollutants and climate change on Arctic marine species. This multidisciplinary approach and the central position of the host institution (Norwegian Polar Institute) in the field of Polar Research will equip the Fellow with a broad set of new skills and lay the foundation for building her specific niche as a future leader in marine pollution science.

Optimization of Free Space Optical Communication Link based Drones for Search and Rescue Operations in the Arctic Region

The Arctic region is witnessing more frequent shipping accidents than ever which require accurate search and rescue operations. The existing communication systems use drones with radio frequency (RF) technology, which has limited bandwidth and cannot offer 4G/5G connectivity due to harsh weather constraints. It further limits the capacity of drones and affects the resolution of images and videos. The current research proposes to design free space optical communication (FSOC) link-based drones that can enhance connectivity between multiple drones and rescue ships as well as the capacity of drones to produce high resolution images and videos. The proposed FSOC-based drones can provide highspeed connectivity than the existing RF technology. The research will collect atmospheric turbulences data from the Arctic region and use it for designing the FSOC link. Furthermore, to enhance the capacity of FSOC-based drones, the research will design advanced multiplexing schemes (Mode Division Multiplexing and Orthogonal Code Division Multiple Access) and to ensure link stability, omnidirectional receiver will be designed. The research will further evaluate the performance of proposed FSOC link under the impact of various atmospheric turbulences. The expected outcomes of this research will lead to the optimisation of FSOC-based drones in expanding search areas and improving communication systems for SAR operations in the Arctic region.

AQUASERV – RESEARCH INFRASTRUCTURE SERVICES FOR SUSTAINABLE AQUACULTURE, FISHERIES AND THE BLUE ECONOMY

The overarching objectives of AQUASERV are to bring together, enhance, integrate and customise RI capacities (including facilities, instruments and expertise) and through the provision of transnational access (on-site or remote) and/or virtual access, to significantly further scientific advance and promote and facilitate the implementation of European Common Fisheries Policy, the Farm to Fork Strategy, the Sustainable Blue Economy and the European Green Deal.   AQUASERV will achieve these objectives by offering scientists from academia and business remote and on-site transnational (TA) and virtual (VA) access to an advanced set of European research infrastructures and its nodes related to research and management of marine and freshwater biological resources, food and biotechnology. These include the European Marine Biological Resource Centre ERIC (EMBRC), the Analysis and Experimentation on Ecosystems ERIC, The Aquaculture for Excellence for Aquaculture in Fish (Aquaexcel), and the Infrastructure for Promoting Metrology in Food and Nutrition (METROFOOD), as well as the International Council for Exploration of the Sea, both a service provider and stakeholder. It also includes the Research Infrastructure for Science and Innovation Policy Studies (RISIS) to bring contributions from the social sciences and to bring results nearer to policy makers ensuring societal impact.   To enhance, integrate and customise RI capacities, collaboration between partners and new pipelines to meet the objectives of the project will be developed during the first 3 years and will make available  to users.  To ensure these capacities will not be lost, a sustainability work package involving stakeholders will address the project legacy.    To maximize impact, AQUASERV will build a communication network among the partnership and develop a dissemination and outreach programme. Furthermore, an advanced training programme will be developed to capture future users and will be updated during the p

Aqua Research Infrastructure Services for the health and protection of our unique, oceans, seas and freshwater ecosystems

AQUARIUS will provide a highly comprehensive suite of integrated research infrastructures appropriate to addressing significant challenges for the long-term sustainability of our unique oceans, seas and freshwater ecosystems. For the first time, diverse research infrastructures will be combined to facilitate the work of researchers and key stakeholders focused on challenges and opportunities for both marine and freshwater systems. An impressive range of 57 research infrastructure services will be made available to include research vessels, mobile marine observation platforms, aircraft,  drones, satellite, sensors, fixed freshwater and marine observatories and test sites, experimental facilities, and sophisticated data infrastructures. AQUARIUS will support the development phase of the EU Mission to Restore our Ocean and waters by 2030, the Sustainable Blue Economy Partnership, the European Green Deal, and international climate initiatives. It will also be an essential component in achieving the European Digital Twin of the Ocean and the UN Decade for Ocean Sciences. The needs of researchers will be met through a robust and transparent system of transnational access funding Calls, facilitated by centralised user-friendly access portal. The Call programme will be informed through stakeholder engagement and brokerage events. Projects to be selected for Access must convincingly integrate multiple infrastructures and contribute to the core policy objectives of Mission Ocean, that is, to protect and restore marine and freshwater ecosystems and biodiversity; to prevent and eliminate pollution of our oceans, seas and waters; and to ensure a sustainable, carbon-neutral and circular blue economy. A thematic and geographic focus will be the hallmark of the proposed transnational Calls, aligning with the Lighthouse Regions, that is, the Baltic and the North Sea Basins, Black Sea, Atlantic/Arctic, and Mediterranean Sea along with their associated rivers.

Advance Marine Research Infrastructures Together

The European Ocean Observing System (EOOS) is the foundation of European ocean knowledge. The core Marine Research Infrastructures (MRIs) focused on ocean observing (EMSO, EURO-ARGO and ICOS ERICs; EuroFleets+, EuroGoShip, GROOM RI, JERICO RI and MINKE as INFRA projects) are the main providers of in situ ocean data for the EOOS and Copernicus, and the primary managers of instrumental capacity supporting fundamental research. These MRIs are aware that the lack of effective cross coordination prevents them from fully supporting frontier research, while the lack of integration makes it difficult to reach a critical mass for EOOS and results in significant cost duplication. Accordingly, AMRIT gathers these MRIs together with OceanOPS/WMO international coordination experience with the objective to: - ensure seamless operation of marine observation platforms ; - ensure the full nominal use of sensors and accelerate their evolution ; - exploit the complementarity of the various observation platforms ; - ensure the overall coherence of the ocean data value chain. To achieve these objectives, AMRIT will design and implement an EOOS Technical Support Center (EOOS TSC) for - a fully integrated information service across the data value chain from early planning stages to final delivery to users; - a cross-platform fully standardised data acquisition methodology for Essential Ocean Variables; - a collaborative federal structure to operate these services, relying on the ERIs and their members. The EOOS TSC will be the cornerstone in establishing and maintaining the EOOS, upon which European ocean observing can be strengthened in the coming decades. AMRIT will provide a catalyst for the development and consolidation of MRIs throughout Europe, providing a benchmark for operational coordination and collaboration. AMRIT will advance EOOS in line with its 2023-2027 Strategy and beyond, and the European Commission's ambitions for sharing responsibility in ocean observing across Europe.

Improve offshore infrastructure resilience against geohazards towards a changing climate

POSEIDON brings together an interdisciplinary and intersectoral team to deliver a professionally trained next-generation network of Doctoral Candidates to develop a step change in our capacity to identify, map, assess and predict offshore geohazards and in turn produce ground-breaking methods to prevent, mitigate and boost the resilience of current offshore infrastructure under a changing climate. The consortium is formed by experts across EU countries with universities, research institutions, industry partners and a government body to cover a full training programme on scientific and transferable skills.   The programme will undertake critical research across scales (from micro to macro) for seeking the inner links and differences, with an eventual aim to ascertain the pathways and grow our capacity for the enhancement of the existing and the robust development of new offshore infrastructure in the frame of safety and resiliency. In addition to the informed design and implementation of the novel physical/numerical modelling and lab studies, our approach is unique in the solid integration and utilisation of state-of-the-art data science technologies (e.g., data mining, machine learning, etc.) to their full potential. Only through this systematic approach, we can achieve the objectives of understanding the impact of offshore geohazards on our offshore critical infrastructures (OCIs) and developing novel models, tools and designs for future OCIs, such as, wind turbines, pipelines and cables.   The Doctoral Candidates will enjoy a highly integrated, interdisciplinary and intersector training environment, enriched through secondments with the network of non-academics. POSEIDON enables critical learning across all training aspects to ensure that comprehensive, robust and implementable solutions are obtained and validated to face the OCIs climate-resilient building.

POLARIN: POLAR RESEARCH INFRASTRUCTURE NETWORK

The polar regions play a key role in the Earth’s system. They are essential for our climate and are sentinels of climate change, human expansion, and the hunt of new resources. The polar regions are losing ice, and their oceans and land are changing rapidly. The consequences of this polar transition extend to the whole planet and are affecting people in multiple ways. Evidence-based policy recommendations are needed, but the polar regions are difficult to reach, and research infrastructures able to operate in these regions are scarce. To understand and predict key processes in the polar regions and provide evidence-based information, the polar research community needs access to world-class research infrastructure operating in these regions. POLARIN is an international network of polar research infrastructures and their services, aiming at addressing the scientific challenges of the polar regions. The network includes a wide array of complementary and interdisciplinary top level research infrastructures: Arctic and Antarctic research stations, research vessels and icebreakers operating at both poles, observatories, data infrastructures and ice and sediment core repositories. POLARIN will provide integrated, challenge-driven, and combined access to these infrastructures to facilitate interdisciplinary research on complex processes.  POLARIN will: 1.	Provide challenge-driven transnational access to a large portfolio of research infrastructures.  2.	Improve the access to data by improving data availability and interoperability between data infrastructures.  3.	Provide virtual access to data and data services.  4.	Provide data products for the scientific community and decision makers. 5.	Train the young generation of polar researchers in optimally exploiting the infrastructures for their research. 6.	Duly advertise the services offered by POLARIN and engage the infrastructure users to share their research outcomes with society. 

Material Science Innovation for Accelerated, Sustainable and Safe Implementation of Carbon Capture and Storage

MISSION-CCS presents a timely and unique doctoral network designed to deliver the next generation of highly trained researchers and entrepreneurs in the field of material science, specifically focused towards accelerating implementation of carbon capture and storage CCS technologies worldwide and ensuring the sustainable and safe operation of existing and future CCS systems.  The training network combines unique experimental system design and modelling approaches, state-of-the-art analytical technologies and techno-economic analysis to deliver a new generation of researchers and entrepreneurs. The programme of research training centres of delivering Doctoral Candidate Researchers (DCRs) with world-leading technical expertise in material science and engineering relevant to the entire CCS process. MISSION-CCS ensures that the subject-specific technical knowledge of each DCRs is under-pinned by inter-sectorial knowledge whilst also promoting wider innovation skills and relevant training on the techno-economics of CCS, developing experts with breadth of knowledge.  A central aim of the network is to forge a strong cohort culture, by ensuring that peer-to-peer learning and mutual support become the norm, in order to enhance experience. Research-led training activities are strengthened through a dynamic and interactive education based programme delivered by an internationally renowned consortium of academics and industrialists with complementary skills. As part of the training programme, subsequent to an introduction to CCS systems and the specific material science challenges, DCRs will gain knowledge of system design and optimisation, state-of-the-art analytical methods, theoretical modelling, techno-economics, and understand the challenges of exploiting their research. They will also acquire proficiency in project management, communication, entrepreneurship, and innovation; all essential attributes for any modern technical professional.

Land-Sea interface: Let’s observe together!

LandSeaLot will link together in situ, model and earth observations (EO) and connect related communities, citizens and initiatives such as Copernicus, ESA, EEA, GEOSS, EMODnet and the European Digital Twin of the Ocean. These observations will be used in a gap analysis to co-design a common land-sea interface observation strategy and an implementation plan. LandSeaLot participants will simultaneously work on improving: in situ and EO capabilities, models to reduce the model/observations gap and the integration of model, in situ and satellite data. Observation capacity will be increased through tested, improved and guided use of low-cost technology by citizens, facilitated by the network of European marinas. The technologies selected will be piloted in Integration Labs (ILs) together with improved and integrated in situ and EO observation techniques and model outputs. LandSeaLot ILs will cover selected areas in the Black, Aegean, Mediterranean, Atlantic, North and Baltic Seas, with a range of catchment, tidal and meteorological regimes. Experts and citizen science leaders will work in the ILs together with JERICO-RI, DANUBIUS-RI and ICOS-ERIC, and with regional policy makers and managers to tailor integrated observations that will provide them with information to manage societal challenges. These will include assessment of the lateral carbon flux and stock, plastics transfer, nutrients impact on primary production and eutrophication, supporting biodiversity conservation, improving modeling capability and supporting climate change adaptation (storm surge, floods, heat waves, coastal erosion, saltwater intrusion). Data generated in the ILs will be made FAIR available via EMODnet and interoperability, and semantic solutions for existing, international data flows will be developed. Relevant communities will be engaged by workshops, conferences, training, a high-tech summit and by a communication strategy including videos and policy briefs to ensure LandSeaLot’s legacy.

Optimisation of digital catch monitoring and reporting in European Fisheries

 OptiFish will strive to provide technological solutions that will simultaneously improve the sustainability of fisher’s operations, enhance control processes and strengthen society’s trust in their products. OptiFish will develop, test and recommend a set of innovative technologies and tools supported by artificial intelligence (AI) to provide the management, the fishing sector and the scientist with data on catch volumes, catch compositions and the fishing environment.  The goal is to unlock the full potential of technologies such as electronic and genetic monitoring for automated species recognition based on AI and computer vision to reduce discards, unreported landings and unreported fishing activities, ultimately establishing  a fisheries control and enforcement system fit for the digital age. The technologies are not enough alone, it is also critical to consider the combination of technologies and the integration of computer vision models, the wide range of data sources and their subsequent formats, while also addressing stakeholders needs and acceptance.  This goal cannot be achieved by a single project, which is why the aim of OptiFish is to lay a solid foundation for full technological development from which other projects and initiatives can be built. The project will place a strong focus on species recognition in different fisheries equipped with distinctly different catch handling facilities and in different European sea basins.  To ensure that these innovations are relevant to fisheries management, OptiFish has participation from the Norwegian Directorate of Fisheries, and has received written support from the European Fisheries Control Agency (EFCA), the Basque, Danish and Belgian Fisheries authorities.  

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Network of the European Union, Latin America and the Caribbean Countries on Joint Innovation and Research Activities

Tumor-stroma interaksjoner kan hjelpe kreftcellene i å danne dattersvulster (metastaser), og Met-NESTING prosjektet tar sikte på å forstå dette samarbeidet for å kunne foreslå nye målrettede behandlinger. Vi fokuserer spesielt på å kartlegge hvordan kreftcellene utnytter cellulære og løselige faktorer i mikromiljøet for å øke sin spredningsevne og resistens mot legemidler. Dette studeres både i hudkreft (føflekk-kreft dvs. melanom) og brystkreft.
Vi har vist at stromaceller, slik som fibroblaster og endotelceller, stimulerer kreftceller slik at de endrer fenotype og får nye egenskaper. Den nye fenotypen er kjent som en invasiv fenotype, og kjennetegner kreftceller med stor evne til å bevege seg, invadere nytt vev og motstå behandling. I tråd med dette har vi observert at hudkreftceller som mottar støtte fra stromale celler mister følsomhet for vemurafenib, et legemiddel som hemmer mutert BRAFog brukes i klinikken mot føflekk-kreft. Dette funnet innebærer en mulig resistensmekanisme og peker på behovet for å identifisere andre mål enn BRAF for å bekjempe de stroma-støttede hudkreftcellene.
For å finne særtrekk hos hudkreftcellene som lever i samspill med stromaceller versus de som vokser alene, brukte vi såkalte «omics»-teknologier og kartla både genuttrykk og proteiner. Dernest brukte vi legemiddelscreening for å identifisere mulig egnede medikamenter. Vi fant flere kandidater som har potensiale til å hemme stroma-støttede hudkreftceller.
Vi påviste at inhibering av signalmolekylene PI3K og mTOR i hudkreftcellene motvirker effekten av stroma-støtte. Dette kan bety at den stroma-støttede invasive fenotypen er avhengig av et signalnettverk som involverer PI3K og mTOR. Videre observerte vi at slike celler har økt følsomhet for metabolske inhibitorer som motvirker glykolyse og fremmer oksidativ fosforylering. I samsvar med dette har vi vist at celler som går over til den invasive fenotypen foretrekker glykose som forbrenningsvei for å skeffe seg energi (metabolsk reprogrammering). Totalt sett viser våre funn at den stroma-støttede invasive fenotypen foretrekker visse signal- og metabolske veier som kan utnyttes som terapeutiske mål.
Alt i alt fremhever denne delen av prosjektet behovet for fenotype-spesifikke terapier. Vi foreslår design av kombinasjonsbehandlinger for å hindre både stroma-avhengige og uavhengige kreftceller fra å metastasere. Vi foreslår flere kandidater med målrettet effekt på stroma-avhengige kreftceller, og som vi forventer gir bedre totaloverlevelse i kombinasjon med BRAF-inhibitorer, som rammer de stroma-uavhengige kreftcellene.
I prosjektets andre del har vi studert hvordan kreftceller blir påvirket av faktorer som er assosiert med inflammasjon. Vi har undersøkt effekt på kreftcellenes prometastatiske egenskaper, deres følsomhet for legemidler, samt deres fenotype. Resultatene viser at kreftceller aktiveres av S100A4, som vi vet har økt forekomst i det metastatiske mikromiljøet og som hjelper kreftcellene i å metastasere. Aktiveringen medfører at kreftcellene blir mer invasive og øker produksjonen av en rekke inflammatoriske mediatorer. Derved er kreftcellene istand til å rekruttere stromaceller og påvirke dem til å bidra til videre utvikling av sykdommen. Vi har vist at monocytter med dette utdannes til M2-makrofager som hjelper kreftcellene i å innta den invasive fenotypen, samt øker deres evne til å bevege seg og motstå terapi. Slik toveis-kommunikasjon mellom kreftceller og stromaceller har vi påvist i både brystkreft og føflekk-kreft. Denne kunnskapen kaster nytt lys over hvordan S100A4 kan øke kreftcellers aggressivitet, nemlig ved å bidra til et inflammatorisk miljø med korrupte immunceller som støttespillere. 
Våre data tyder på at kreftceller som har invasiv fenotype kan være spesielt egnet til å danne inflammatorisk miljø og engasjere makrofager som støttespillere. Terapi mot den invasive fenotypen kan derfor rette seg mot makrofagene eller inflammasjonsfaktorene som er involvert.

The great majority of cancer related deaths are caused by metastatic disease, and there is an urgent need to develop more effective anti-metastatic therapies. Recently, it has become acknowledged that the tumor microenvironment (including stromal cells, e xtracellular matrix and soluble mediators) can facilitate metastasis by forming a permissive/protective metastatic niche for disseminated tumor cells. Disruption of the niche might be a new therapeutic strategy against metastases, signifying the need to d isclose key players in the formation of such growth permissive environments. 

The aim of the Met-NESTING project is to identify soluble factors, stromal cells and extracellular matrix components contributing to bidirectional tumor-stroma interactions in  the metastatic niche, and to explore whether such factors may serve as targets for anti-metastatic therapy. To achieve this goal, we will use different models mimicking tumor-stroma interactions in vitro, ex vivo and in vivo. 

The project is based on the  hypothesis that the metastasis-promoting protein S100A4 triggers tumor cells to secrete soluble mediators stimulating tumor-stroma crosstalk and contributing to formation of the metastatic niche. The molecular and cellular mechanisms involved in this cro sstalk will be sought unraveled, and by identifying factors essential for orchestrating interactions during development of the metastatic niche, novel therapeutic targets or predictive/prognostic biomarkers may be identified.

Met-NESTING: Metastatic Niche Establishment by Stromal-Tumor INteractions; Going towards novel therapies

Målsetningen for MetAction har vært å bidra til at ny kunnskap innen kreft og kreftutvikling skal komme den enkelte pasient til nytte i form av mer målrettet behandling. Prosjektet har vært organisert med fokus på tre hovedaktiviteter: 1) planlegging og gjennomføring av en klinisk studie der behandling av metastatisk sykdom bestemmes ut fra det spekter av genetiske endringer som finnes i svulsten (såkalte Next Generation Sequencing data); 2) gjennomføring av en eksplorative studie for å avdekke nye ?actionable targets? i metastatisk vev; 3) utvikling av bioinformatiske verktøy nødvendig for å gjennomføre de to nevnte aktivitetene. 

Aktivitet I ? Identifisering av molekylære avvik i metastatisk tumor og gjennomføring av utprøvende behandlingsstudie:

Mutasjoner i enkeltgener er innført som behandlingskriterium i enkelte kreftformer, men det har aldri tidligere vært gjennomført kliniske studier her i landet der en bred undersøkelse av gensignaturer danner grunnlaget for behandlingsvalg. Den viktigste oppgaven for MetAction var derfor å planlegge og gjennomføre en klinisk studie der NGS-data sammen med klinisk informasjon dannet grunnlaget for valg av behandling for pasienter med kreftspredning. Studien ble godkjent av Statens Legemiddelverk desember 2013 og totalt 50 pasienter har vært inkludert ved de to studiesentrene, Akershus Universitetssykehus og Oslo Universitetssykehus. 
Den første delen av prosjektet besto av å etablere en arbeids- og informasjonsflyt for diagnostiske prosedyrer. Oppsummert besto dette av rutiner for bildeveiledet prøvetaking (biopsering) av metastatisk svulst, målrettet DNA-sekvensering, etablering av molekylært beslutningspanel (MTB) for tolkning av molekylære data og klinisk beslutningspanel (CTB) for integrasjon med klinisk informasjon. I første del av studiet ble 24 pasienter inkludert, men ingen behandlingsmulige molekylære avvik ble identifisert. Modellering av kostnader for tre måneders pasientoppfølging tilsa at MetAction-strategien var 2,5 ganger mer kostbar enn ikke-tumorrettet symptombehandling. Studien var midlertidig lukket mens vi fikk godkjenning for tre prinsipielle protokollendringer: 1. Bytte av diagnostisk genmutasjonspanel fra ?hotspot?-basert til ?comprehensive?-panel; 2. Utvidet frihet for MTB til å tolke mutasjonsdata; 3. Mulighet for CTB å tilråde kombinasjonsregimer (gitt etablerte sikkerhetsdata). I andre studiedel inkluderte vi 26 pasienter, hos 13 identifiserte vi behandlingsmulige molekylære avvik, og 10 fikk startet behandling. Av disse nådde 6 pasienter studiens primære endepunkt (progresjonsfri periode på studiemedisin med varighet lenger enn 1,3× progresjonsfri periode på siste linje standardbehandling). Det er verd å merke seg at 4 pasienter (4/26 = 15%) har oppnådd langvarig respons på studiebehandling og således har fått reversert sitt sykdomsforløp.

Aktivitet II - Eksplorativ studie for å identifisere nye targets i metastatisk vev:
Det er prosessert vevsprøver og isolert DNA og RNA fra pasienter med metastastisk malignt melanom (MM; n=54 lymfeknutemets), tykktarmkreft (CRC; n=51 levermets/normalt vev) eller brystkreft (BC; n=50 lymfeknutemets) for å studere tumor heterogenitet og identifikasjon av mulige «actionable targets». Genomiske analyser har inkludert identifisering av mutasjonsstatus i kjente kreftassosierte gener, kopitallsvariasjon- og genekspressjonsanalyser. 
Vi har påvist en assosiasjon mellom immune-relaterte mekanismer og utvikling av levermetastaser fra CRC (Østrup et al, 2017), og har på bakgrunn av dette gjennomført en kvantitativ immunohistokjemisk undersøkelse av immunceller i metastasene (manuskript under utarbeidelse). Videre har vi identifisert en gensignatur som representerer en tumor fenotype som innehar egenskaper til å påvirke polarisering av immune celler. Ekstrahering av immunprofiler fra MM panelet er pågående og vil komplementere resultatene fra genekspresjons-og mutasjonsanalysene. Vi sammenligner også molekylære data fra metastaser på tvers av alle svulsttyper, med særskilt fokus på identifisering av fellestrekk mellom disse ulike kreftformene. Våre data tyder på at den molekylære signaturen fra primærtumor er bevart, men visse fenotypiske egenskaper (f.eks. metabolske prosesser), synes å ligne på hverandre i metastaseprøvene uavhengig av pasientens primærdiagnose. 
Vi har også utvidet panelet av metastatiske prøver til å omfatte 57 hjernemetastaser (32 MM, 13 BC, 12 CRC). Disse har gjennomgått målrettet DNA og RNA sekvensering. Målsetningen er å identifisere klinisk relevante molekylære profiler for å kartlegge muligheter for målrettet behandling av metastatisk sykdom i hjernen. 
Aktivitet III - integrated bioinformatics. De nødvendige prosedyrer for gjennomføring av klinisk protokoll har blitt etablert i en tidligere fase av prosjektet og har blitt utnyttet ifm tolking av data fra inkluderte pasienter.

The MetAction vision is to move from bed ? to bench ? to byte ? to bedside. By facilitating multidirectional flow of ideas and knowledge between clinical and basic research groups we aim to translate recent progress in cancer biology into clinical benefit . The great majority of cancer related deaths is caused by metastatic disease, and for personally-adapted treatment it is essential to molecularly characterize the metastases and choose therapy based on rate limiting and actionable targets present. 

By a dapting therapy to the individual cancer patient the expectation is to improve treatment efficacy, reduce toxicity and minimize cost in cancer care. To achieve this goal we have to increase our knowledge on molecular changes driving tumor progression - th ereby defining the rate limiting and actionable targets. In addition, biomarkers must be identified allowing reliable identification of patients likely to respond and to demonstrate response upon molecularly-driven therapy. Finally, for clinical utilizati on the molecular portrait of the tumor has to be interpreted in the context of patient parameters to decide on optimal therapy. This puts new demands on the clinical team in charge of patient management and an important goal for the MetAction project is t o sophisticate multi-disciplinary teams and infrastructure to create a solid basis for personalized cancer medicine.

By molecular profiling of metastatic tumors in a palliative setting MetAction will gain knowledge that relatively quickly can be translat ed into clinical benefit. The multilevel molecular characterization and integrative computational analyses will further enhance the understanding of cancer progression and novel actionable targets and biomarkers will be identified.

MetAction: Actionable Targets in Cancer Metastasis - from Bed to Bench to Byte to Bedside

Purpose of the project:
Few protocols have so far been designed with attempts to characterize the systems biology of cancer. The objective of the project is to translate information obtained from integrative molecular analysis of material collected from i ndividual cancer patients, through validation of the obtained results in functional studies, into development of better and more personalized methods for diagnosis, prognosis and treatment of breast cancer. 

R&D challenges:
Efforts to characterize the sy stems biology of individual cancer patients give rise to an enormous amount of data. Efficient bioinformatics tools integrating all the experimental data and comparing the molecular profiles with the clinical information is of outmost importance for being  able to draw valid conclusions.
A small population of cancer stem cells has been hypothesized to initiate and sustain a tumor. Investigations of the importance of this small cell population will be performed as targeting and eradicating such slow cycling  and treatment resistant cells will be essential for successful treatment. 

Applications:
The inherent heterogeneity that characterize all malignant tumors are only partly apprehended in the parameters that at present help the clinicians decide upon diag nosis, prognosis and selection of therapy, and one fourth of all breast cancer patients experience relapse and metastatic disease. Thus, development of therapies designed to each individual patient, is highly needed. By ensuring access to matched material  from the primary tumor, disseminated cells in bone marrow, micrometastatic lesions in sentinel lymph nodes and metastatic tissue, the project has a unique possibility to follow the molecular changes during tumor progression and identify possible target m olecules for utilization as diagnostic, prognostic and therapeutic markers.

Towards personalized therapy for breast cancer

The calcium-binding protein S100A4 has convincingly been linked to the metastatic process, butt he exact mechanism of action is still unknown.  The main purpose of the project is to study the molecular mechanisms behind some of the biological functions th at have been suggested tor the protein, and investigate how these functions might have impact on the metastatic phenotype.  Obtained results show that the protein exists both in the extracellular space, in cytoplasm and also in the nucleus of tumor cells.  Our hypothesis is that the protein might have different functions depending on factors like cell system, localization and availability of interacting protein partners, topics that will be investigated in the suggested project.  We will focus our work on studies of two observed phenomena: impact of secreted S100A4 on induction of invasion, as well as certain types of apoptosis, and S100A4-DNA-protein interactions and possible involment in transcriptional regulation.

Cancer metastasis is a complex process  and knowledge about how to prevent cancer metastasis is one of the most challenging tasks in cancer research.  Functional studies of involved gene products are of fundamental importance for the understanding of the biological mechanisms causing metastats is formation, and further development of new therapeutic strategies.


INCO-4.07 Activities of International cooperation

Network of the European Union, Latin America and the Caribbean Countries on Joint Innovation and Research Activities

Tildelt: kr 0,42 mill.

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INCO-4.07 Activities of International cooperation

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