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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.


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.

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.

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.



Metabolisme og signalisering mellom vitamin-avledede kofaktorer - en læringsplattform for systemmedisin

Midlene fra INTPART-International Partnerships for Excellent Education and Research fordelt på år

Midlene fra INTPART-International Partnerships for Excellent Education and Research fordelt på fylker

Midlene fra INTPART-International Partnerships for Excellent Education and Research fordelt på fagområde

Head of department/Professor

Systemmedisin har vist seg som et viktig fagfelt for å identifisere sykdomsmekanismer og biomarkører, samt følge og forutsi effekten av behandlinger og for å utvikle nye kombinatoriske terapier. Vi ønsker å utvikle og implementere et eget studieprogram innen systemmedisin i Norge. Dette prosjektet vil samle et team av ledende eksperter fra fem anerkjente akademiske institusjoner [i Norge (2), USA (1) og Russland (2)]. De vil utvikle en unik portefølje av systemmedisinsk opplæring - fra molekylære mekanismer til sykdomsbehandling. Kursene vil omfatte eksperimentelle og beregningsmessige analyser av metabolske veier og signalnettverk, kreft relatert biokjemi, avanserte analytiske teknikker, matematisk modellering og maskinlæring samt prinsipper for medikamentutvikling. Basert på veletablerte vitenskapelige samarbeid mellom alle partnere, vil UiB koordinere prosjektet. Praktiske kurs vil bli gjennomført ved de aktuelle partnerinstitusjonene.
I denne prosjektperioden ble vi utfordret av hendelser som gjorde det nødvendig å justere sammensetningen av konsortiet og tidsplanen for våre aktiviteter. På den ene siden, i slutten av 2021/begynnelsen av 2022, var det fortsatt restriksjoner på plass på grunn av pandemien. På den annen side gjorde krigen i Ukraina det umulig å fortsette samarbeidet med partnerne fra Russland. Derfor innledet vi med støtte fra Norges forskningsråd et nytt samarbeid med et ledende systemmedisinsk miljø ved Universitetsmedisinsk senter Groningen (UMCG, NL). Sammen med UMCG utviklet og implementerte de tre andre partnerne (UiB, UiT, Univ. of Southern Alabama) en ny plan for kurs, utveksling, møter og workshop-aktiviteter. Denne planen er nå vedtatt, og vi har gjennomført en rekke aktiviteter siden midten av 2022 (med aktiv deltakelse av minst to partnere og deltakelse av PhD- og masterstudenter fra alle partnerinstitusjoner):
-	Workshop: Evolutionary aspects of sequence analysis (12-14 June 2022, Tromsø)
-	The FASEB NAD metabolism and signaling conference (26 June – 1 July 2022, Steamboat, AZ)
-	International Study Goup for Systems Biology Conference (19-23 September 2022, Innsbruck)
-	Workshop: Interdisciplinary communication in Systems Biology (16-19 February 2023, Tromsø)
-	VitaCross Symposium: Research training in vitamin biology (6-7 January 2023, University of South Alabama, Mitchell Cancer Center, Mobile, AL) - streamed and with contributions from partners and guests, in part, online
-	PhD/Master Course: Modelling in Systems Biology I -Metabolic pathway modelling (20-24 February 2023, Tromsø)
Samlet sett har vårt arbeid med å tilpasse vårt konsortium og aktiviteter til den nye situasjonen vært vellykket. Det nye konsortiet er nå godt etablert og har utformet en oppdatert tidsplan for systematiske kurs i systemmedisin, workshops og symposier for 2024-2026.

Systems medicine has emerged as essential discipline to identify disease mechanisms and biomarkers, follow and predict the effect of treatments and to develop new, combinatorial therapies. To our knowledge, dedicated study programs in systems medicine do net yet exist in Norway. This project will bring together a team of leading experts from four renowned academic institutions [in Norway (2), the United States (1) and the Netherlands (1)]. They will develop a unique portfolio of systems medicine training – from molecular mechanisms to disease treatment. The courses will include experimental and computational analyses of metabolic pathways and signaling networks, chemical biology of cancer, advanced analytical techniques, mathematical modelling and machine learning as well as principles of drug development. Based on well-established scientific collaborations with all partners, UiB will coordinate the project. Practical courses will be conducted in the relevant partner institutions. The EU consortium on systems medicine of breast cancer (MESI-STRAT) and the NeuroSysMed center (FKB, Bergen) will support this initiative with their competences.
This INTPART project will also significantly contribute to the scientific excellence of existing joint research projects among all parners. A major focus will be on the biology and medical significance of coenzymes derived from vitamin B precursors, a hot area of current biomedical research both in metabolomics, signaling and for the development of nutritional therapeutic concepts. 
Collectively, the project will enable tight collaborations with outstanding academic environments in systems medicine, beyond existing EU initiatives, to develop world-class training in systems medicine. Moreover, it will provide the opportunity for outstanding research that no partner institution on its own would be able to conduct. Thereby, the new generation of scientists in biomedical research will be adequately prepared for the challenges ahead.

Metabolic and signaling crosstalk of vitamin-derived cofactors - a training platform for systems medicine

Brystkreft er den vanligste kreftformen blant kvinner i Norge, med mer enn 3000 nye diagnoser i 2020. Dødeligheten er hovedsakelig et resultat av spredning av kreftceller, med påfølgende dannelse av svulster i nye organer.  Mange pasienter har effekt av kreftmedisinene tilgengelig per i dag, men en stor andel vil likevel få tilbakefall og utvikle kreft resistent mot denne type behandling. Dette fører ofte til spredning av kreften, med  få eller ingen effektive medisiner mot dette. Derfor er forståelse av kreftspredning essensiell for å kunne finne både nye metoder for diagnostisering, og nye behandlingsformer for disse pasientene. 
En tumor består i tillegg til kreftceller, av flere andre celletyper. Disse inkluderer blant annet diverse immunceller, og i dette prosjektet ønsket vi å se nærmere på hvordan tumoren kan påvirkes av spesielt en type immunceller, kalt makrofager. Dette er spesielt interessant siden disse immuncellene kan legge til rette for tumorvekst, men også hjelpe kreftcellene til å bli mindre mottakelige for kjemoterapi. Ved å undersøke signalene som sendes mellom brystkreftceller og disse immuncellene i tumoren, vil det være mulig å identifisere sentrale faktorer som er viktige for tumorens evne til å tilpasse seg behandling, samt hvordan immuncellene brukes til å legge til rette for dette. 
Våre data viser hvordan nye behandlingskombinasjoner i en dyremodell for aggressive brystkreft kan redusere tumorvekst ved å både øke effekten av cellegift i selve tumoren, men også ved å redusere spredning til andre organer. Siden mekanismen bak denne økte responsen fortsatt er uklar, valgte vi å bruke forskjellige såkalt «high-throughput» metoder for å få en generell oversikt over aktiviteten i tumor og immunceller, og kommunikasjonen mellom disse etter behandling. Slike metoder samler inn store mengder data fra f.eks. alle gener og/eller celler som finnes i en tumor. På den måten kan vi undersøke hvordan spesifikke celler endrer seg under behandling, og hva som skiller disse i tumorer som responderer på behandling. Dette er spesielt relevant for immunceller, som basert på hvilke gener de utrykker, enten kan legge til rette for eller motvirke tumorvekst. 

Flow cytometri (som blant annet lar oss identifisere endring i immunceller) av tumorprøver fra dyr behandlet med kjemoterapi sammen med de forskjellige målrettede behandlingene, viste redusert antall pro-tumor makrofager (som normalt hjelper fremveksten av tumorceller). Vi kunne også se økning i andre immuncellepopulasjoner som er gunstig for å motarbeide kreftcellene, og som er en god indikasjon på at behandlingene har ønsket effekt. For å undersøke hvilke endringer disse tumorene gikk gjennom, gejnnomførte vi RNA-sekvensering (RNA-seq) av behandlede tumorer. Dette lot oss undersøke hvordan gener endrer seg som følge av behandling. Disse dataene ble så sammen med proteindata fra flow cytometri brukt for å validere endringer etter behandling. For å bedre forståelsen av respons på behandling gjorde vi så single-cell RNA-seq (scRNA-seq), som lar oss se på enkeltcellers endring som følge av behandling. Dette kan være spesielt gunstig om kun en mindre populasjon av celler er viktig, siden disse signalene vil være vanskelig å identifisere ved vanlig RNA-seq (som kun gir et oversiktsbilde over hele tumoren). Ved hjelp av disse metodene identifiserte vi endringer som ser ut til å være sentrale i responsen til behandling (eller fravær av denne), både for konvensjonell kjemoterapi, men også de nye behandlingsmetodene testet i dyremodeller. Disse observasjonene ble så bekreftet ved å se etter tilsvarende endringer i både datasett tilgjengelig fra tidligere studier og gjennom andre pågående studier i forskningsgruppen ved OHSU, hvor preliminære pasientdata er tilgjengelig for noen av de nye behandling vi har testet ut i dyr. På den måten har vi mulighet til å relatere funnene i dyr til pasientmateriale. På samme måte, ble pasientdata tilgjengelig ved forskningsgruppen i Norge brukt til å bekrefte funn knyttet til fravær av respons på vanlig kjemoterapi.  
For øyeblikket arbeides det med å ferdigstille de siste analysene for ytterlige detaljer rundt hvilke signaler og immunceller som er viktig i respons på behandling. De endelige analysene vil så bli sendt for publikasjon i internasjonalt anerkjente tidsskrifter for kreftforskning. Disse studiene vil ikke bare gi informasjon om nye alternativ for behandling av pasienter med få alternativer per i dag, men vil også være viktig i videre forståelse av hvordan kreftceller kan omgå effekten av kjemoterapi i pasienter med brystkreft og identifikasjon av hvilke pasienter som er mer utsatt for nettop dette.

Cancer is among the most common mortality factors in the western world. Many patients benefit from conventional therapy, nevertheless, a large subset experiences relapse and develops drug resistance. Eventually many of these patients will progress into metastatic disease, of which treatment is inadequate and in most cases not curative. Thus, there is an urgent clinical need for more effective anti-metastatic therapy. 
In addition to the cancer cells, tumors consist of distinct stromal cells, like tumor-associated macrophages (TAMs), and the dynamic interactions between these cells are crucial for growth and survival. Such interactions are also essential when cancer cells switch their phenotype to a more aggressive mesenchymal state, promoting metastatic progression and treatment resistance. By characterizing central nodes involved in this process, therapeutic targets with potential impact on clinical management of metastatic disease may be identified.
This project aims to use an animal model of metastatic breast cancer, PyMT, to elucidate the bi-directional communication between the cancer cells and TAMs. Preliminary data has shown that targeting pro-tumorigenic TAMs (with Paclitaxel and anti-CSF1R) prior to treatment with immunotherapy (aPD-1), improves survival and reduces tumor growth. We are interested in identifying how addition of aPD-1 impacts the remaining TAMs. Particularly interesting is also the observation that animals treated with the triple combination can be divided into two distinct subgroups, responders and non-responders. In the present project we will elucidate whether the differences in response to treatment is due to differences in the macrophage compartment. Initially through use of bulk RNAseq, to identify large scale changes in the transcriptome of tumor responding and not responding to treatment. By combining this with single cell RNA-sequencing (scRNAseq) we would identify not only broad specter changes in tumors after treatment, but also cell specific changes in macrophages, as well as other distinct immune cell populations. This will allow us to examine how the addition of aPD-1 affect these, and whether specific signatures or targets can be used to identify responders and non-responders. Changes in expression of macrophages would be validated, before potential targets will undergo stringent evaluation in vitro before immune-competent mice will be used to validate the targets/factors. Finally, the clinical relevance of potential targets will be validated utilizing tumor tissue collected from breast cancer patients. 
We anticipate that through this study novel therapeutic targets/strategies and/or biomarkers to tailor phenotype-based treatment against metastatic cancer will be revealed.

0 antall prosjekter

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Tumor-macrophage Interactions - The Promised Land for Identifying Novel Anti-cancer Targets

Tildelt: kr 3,5 mill.

Prosjektperiode: 2018-2022

Sted: Oslo