2015

2014

2013

2012

2011

2010

2009

2008

2007

Portefølje Naturvitenskap og teknologi ikon

The research system

Portefølje Humaniora og samfunnsvitenskap ikon

Ground-breaking research

Portefølje Samisk ikon

Sámi society and culture

Portefølje Demokrati, styring og fornyelse ikon

Democracy and global development

Portefølje Velferd, kultur og samfunn ikon

Welfare, culture and society

Portefølje Helse ikon

Health

Portefølje Klima- og polarforskning ikon

Climate and environment

Portefølje Landbasert mat, miljø og bioressurser ikon

Land-based food, the environment and bioresources

Portefølje Energi, transport og lavutslipp ikon

Energy and transport

Portefølje Muliggjørende teknologier ikon

Enabling technologies

Portefølje Industri og tjenestenæringer ikon

Innovation

LTP Climate, environment and environmentally friendly energy

Climate and loss of natural diversity

Internationalization

Societal security and civil preparedness

Renewal in the public sector

Velferdstjenester

Frontpage Image

Marine icon

Petroleum og mineraler

LTP Hav ikon

Oceans and coastal areas

LTP2 Muliggjørende og industrielle teknologier ikon

Enabling and industrial technologies

Trust and community

Professional environment

High quality and accessibility

LTP Climate

Strengthened competitiveness and innovation capacity

LPT Health

 An innovative business community

LTP2 Styrket konkurransekraft og innovasjonsevne ikon

LTP2 Utvikle fagmiljøer av fremragende kvalitet

LTP2 Samfunnssikkerhet og samhørighet ikon

LTP2 Fornyelse i offentlig sektor ikon

LTP2 Klima, miljø og miljøvennlig energi ikon

LTP3 Helse

Portefolje Petroleum Ikon

Portefølje Hav ikon

Portefølje Utdanning og kompetanse ikon

Portefølje Global utvikling og internasjonale relasjoner ikon

Portefølje Livsvitenskap ikon

Forsidebilde optimalisert

project-bank-technical

Et innovativt næringsliv ikon

Muliggjørende teknologier bakgrunn

Marin bakgrunnsbilde

Marin ikon

Forsidebilde

Statistics

Prosjektbanken presenterer statistikk og informasjon om prosjekter med finansiering fra Forskningsrådet fra 2004. Statistikken er fordelt på blant annet tema, år, geografi og organisasjon. Prosjektbanken gir også detaljert informasjon om de enkelte prosjektene.

...or see the summary and other information about the projects you have selected

Forside

How the grants are distributed between organisations, counties, subject areas etc....

Here are some examples of searches you can perform in the Project Databank

Portfolios

En god beskrivelse av denne siden for søkemotoroptimalisering

All long term plan objectives

About Text Queries

No thematic area or topic related to the project

has received funding in the programme period

No popular science description is available

have received funding in the programme period

The project with project number {{project number}} was not found

Technical description

Woops, something went wrong. Please refresh the page. If the error persists, please contact us.

We could not find what you were looking for

See statistics related to this LTP objective

See projects related to this LTP objective

related to this LTP objective have received grants

has been granted to projects related to this LTP objective

has been granted to projects related to this portfolio

related to this portfolio have received grants

About Prosjektbanken

Kunnskapsdepartementet

Olje- og energidepartementet

Ukjent

Matematikk og naturvitenskap

Teknologi

Oslo

Trøndelag - Trööndelage

Troms - Romsa - Tromssa

Vestland

LTP3 Styrket konkurransekraft og innovasjonsevne

LTP3 Et kunnskapsintensivt næringsliv i hele landet

LTP3 Høy kvalitet og tilgjengelighet

LTP3 Fagmiljøer og talenter

LTP3 Rettede internasjonaliseringstiltak

LTP3 Klima, miljø og energi

LTP3 Miljøvennlig energi og lavutslippsløsninger

LTP3 Klima, polar og miljø

LTP3 Muliggjørende og industrielle teknologier

LTP3 Nano-, bioteknologi og teknologikonvergens

UoH-sektor

Instituttsektor

Øvrige

Portefølje Forskningssystemet

Portefølje Banebrytende forskning

Portefølje Innovasjon

Portefølje Energi og transport

Portefølje Muliggjørende teknologier

Portefølje Klima og miljø

Grunnforskningsprogrammer

Programmer

Frittstående prosjekter

Nettverkstiltak

Tilskudd

Infrastruktur og institusjonelle tiltak

Forvaltning

Diverse FoU-relaterte aktiviteter

Felleskostnader

Italia

Sverige

Forskerprosjekt

Koordinerings- og støtteaktivitet

Internasjonalisering

Grunnforskning

Bransjer og næringer

Energi

Klimarelevant forskning

Naturmangfold og miljø

Nanoteknologi/avanserte materialer

Klima

Miljøteknologi

Politikk- og forvaltningsområder

Globale utfordringer

Forskere har lenge debattert om spesifikke endringer i måten genene våre reguleres på, kalt epigenetiske endringer eller "epimutasjoner," kan øke risikoen for kreft. Våre nylige banebrytende undersøkelser har gitt sterke bevis på at epimutasjoner faktisk er en risikofaktor for visse typer kreft.
I en studie av en stor gruppe kvinner fant vi at de som hadde epimutasjoner i BRCA1-genet, hadde mye større risiko for å utvikle trippel-negativ brystkreft og høygradig serøs eggstokkreft senere i livet. Disse epimutasjonene ser ut til å oppstå tidlig under fosterutviklingen, og fører til at det fødte barnet (og senere det voksne individet) har en mosaikk av celler i kroppen, der noen få celler bærer epimutasjonen.
Nå har vi som mål å utvide disse studiene til andre gener og andre former for kreft. For å gjøre dette vil vi analysere blodprøver fra en studie som har rekruttert over 160 000 kvinner i USA.
Hvis denne forskningen lykkes, kan den revolusjonere vår forståelse av hvordan kreft utvikler seg og føre til bedre forebyggende tiltak. Det kan også ha store implikasjoner for kreftscreeningprogrammer og genetisk veiledning for personer med høy risiko for visse typer kreft.
Alt i alt fremhever vår forskning den viktige rollen som epigenetiske endringer kan spille i kreftutvikling og understreker behovet for ytterligere undersøkelser på dette området.

Cancers result from accumulation of genetic and epigenetic alterations. The minority of cancers are due to inherited (germline) alterations that affect all cells in the body. On the other hand, the majority of cancers (>85%; sporadic cancers) are believed to occur due to localised alterations that accumulate after birth as a result of stochastic processes and/or environmental effects. Recently, in a major breakthrough work, we have provided definitive evidence that some sporadic cancers arise in adult life due to mosaic BRCA1 epimutations that occurred during the early embryonic development. BRCA1 epimutations have a surprisingly high population frequency (>5% of adult women) and hazard ratios for breast and ovarian cancer (2.4 and 1.9, respectively). Together with the findings of epimutations in other tumour suppressor genes (MGMT, MLH1, etc) this has led us to hypothesise that a substantial fraction of other sporadic cancers can be attributed to prenatal epimutations in other tumour suppressor genes.

In this project, we will use ultradeep targeted methylation sequencing for quantitative and qualitative analyses of epimutations. Evaluation of cancer risk related to epimutations will be done by studying samples from prospective biobanks (WHI) with samples from healthy women that remained cancer-free or developed different types of incident cancers years/decades after samples were taken. We will also characterise epimutations present in samples of newborn boys and girls, as well as their parents (MoBa biobank). Finally, using cryopreserved blood-derived stem-like cells from young healthy males and female breast cancer patients (in-house biobank), we will assess mutational and epimutational mosaicism at the single-cell level, generating clonal phylogeny for the methylated cells and thus providing insights on early-developmental processes that create epimutations.

Mosaic epimutations: population prevalence, mechanistic origins, and their role in cancer

Cøliaki er en sykdom som rammer 1-2% av befolkningen. Den eneste eksisterende behandlingen for sykdommen i dag er en livslang glutenfri kost. Det er ønskelig å utvikle alternative behandlingsmetoder. Nyere forskning har avdekket at enzymet transglutaminase 2 spiller en sentral rolle i utviklingen av sykdommen. Dette enzymet forandrer glutenproteiner slik at immunsystemet hos cøliakere kan reagerer på disse proteinene. Denne immunresponsen hos cøliakere involverer B-celler. B-celler produserer antistoffer, og cøliakere har B-celler og antistoffer som er rettet mot transglutaminase 2. I projektet ønsker vi å ta denne kunnskapen i retning mot utvikling av nye behandlingsprinsipper. En del av prosjektet dreier seg om hemming av enzymaktiviteten til transglutaminase 2, og å avdekke hvor i kroppen hvor transglutaminaseaktiviteten bør hemmes. En annen del av prosjektet dreier seg om å finne en metode som kan elimimere B-cellene som gjenkjenner transglutaminase 2.  Prosjektet vil studere celler og vev fra cøliakere samt mus som er genetisk modifisert til å uttrykke reseptorer som brukes av cøliakere til å gjenkjenne gluten og transglutaminase 2.

Celiac disease is a prevalent autoinflammatory condition caused by immune reaction to dietary gluten proteins. The only available treatment is lifelong avoidance of dietary gluten. However, symptoms and enteropathy often persist in patients who attempt to adhere to a gluten-free diet. Thus, there is a need to develop non-dietary therapies for celiac disease. 

The enzyme transglutaminase 2 (TG2) has critical roles in celiac disease pathogenesis. The enzymatic activity of TG2 creates by deamidation gluten peptides that have high affinity for disease-predisposing HLA-molecules, and these deamidated peptides are recognized by the disease-driving CD4+ T cells. Moreover, TG2 is the target of a highly specific autoantibody response. In this project we will explore two novel treatment avenues focused on TG2. In the first approach, we seek to develop novel immunotherapeutic molecules, Bispecific AutoAntigen T-cell Engagers (BiAATEs), to specifically eliminate the subset of autoreactive TG2-specific B cells while avoiding general immunosuppression. The results will be important not only for celiac disease but also for other autoimmune diseases having cytosolic autoantigens.

Second, we will explore therapeutic inhibition of TG2. ZED1227, an irreversible inhibitor of TG2, was recently shown in a phase 2 clinical trial to prevent gluten-induced intestinal damage in celiac disease patients. It is however unknown where in the body the drug is active. Our group has obtained evidence that the gut lumen likely is the relevant site where TG2 is active and encounters gluten peptides for deamidation. We will test the new hypothesis that TG2 in gut lumen is pathogenic in celiac disease and will explore inhibition of gut luminal TG2 as therapy.  

Both arms of the project will combine studies on patient samples with mechanistic experiments in state-of-the art humanized mouse models that we recently developed.

Exploring novel therapies for celiac disease centered around the autoantigen transglutaminase 2

Kreftvev inneholder ikke bare kreftceller, men også en rekke forskjellige immunceller. Noen av dem er nyttige, andre bytter side og hjelper nå svulsten. Kunnskapen om fordelingen av immuncelletyper til en pasient er svært viktig. Denne informasjonen er med på å definere den beste personlige behandlingen, gi en klarere overlevelsesprognose eller hjelper å definere nye mulige behandlingsalternativer. 
I tillegg gjennomgår immunceller i tumormikromiljøet flere endringer, noen er nyttige i kampen mot kreft, andre hjelper svulsten til å vokse eller spre seg. Kunnskapen om disse endringene i de ulike immuncelletypene hjelper til med å forklare prosessene i svulsten eller til å oppdage mulige nye biomarkører for behandlingsalternativer. 
I dette prosjektet ønsker vi å ta hensyn til både den romlige fordelingen og endringene av de forskjellige immuncelletypene avhengig av deres lokalisering i forhold til kreftvev. Hvilke endringer kan vi finne? Hvordan påvirker de hverandre og hvordan påvirkes de av svulsten? Vi ønsker å bruke denne kunnskapen til å oppdage nye mulige biomarkører for behandlingsalternativer.

Spatial transcriptomics provides unprecedented details about the molecular mechanisms that take place within and between cells. ST assesses the molecular content of well-defined regions in a tissue which potentially cover contributions from multiple cells. In order to draw correct biological conclusions from ST analysis, spatial distributions of individual cell types are a prerequisite. This generates an urgent need for computational methods addressing this question. However, computational estimates of cellular compositions from ST are complicated by several factors. First, the methods require well curated data which is usually not available; every specimen has its own individual characteristics and so, every tissue type or even every patient, might require a own, comprehensively verified model. Second, data is noisy, making estimates prone to errors. Moreover, even if a computational model is designed for a specific tissue or even patient, it might be miss-specified, leading to additional systematic errors. In this project, we will develop a toolbox called Computational Dissection of Cellular Distributions (CDCD), which directly accounts for these issues. CDCD will advance the state of the art by (1) taking into account a priori unknown, hidden cellular background contributions, (2) taking into account environmental factors (i.e., tissue and patient dependence), and by (3) comprehensive errors estimation. Intriguingly, in contrast to available techniques, CDCD will facilitate estimates of cellular regulation in space! Such gene-regulation gradients will allow us to address questions of how immune cells adapt their molecular phenotype with respect to their environment. Additionally we will verify our algorithms on a conjoint norwegian phase II melanoma case study. CDCD will be made freely available via easy-to-use webpage and software solution, enabling both expert bioinformaticians and wet-lab biologists an efficient use of the to-be-developed methodology.

Computational dissection of cellular distributions and cell-type specific regulation patterns from spatial transcriptomics data

I møte med utfordringene ved en aldrende befolkning i Europa, utvikler dette prosjektet bærekraftige øyedråper basert på hydrogeler utvunnet fra plantebaserte forbindelser, for å motvirke aldersrelaterte forandringer i netthinnen.

De bio-baserte hydrogelene er utviklet for å fjerne skadelige avleiringer, redusere betennelsestilstander og forbedre oksygentilførselen til netthinnen – faktorer som er sentrale for å bevare synet og opprettholde cellenes energiomsetning.

I motsetning til eksisterende behandlinger benytter denne tilnærmingen miljøvennlige materialer og unngår invasive prosedyrer, noe som gir en tryggere og mer tilgjengelig løsning for personer med aldersrelaterte øyesykdommer.

Sustainable self-cleaning hydrogels in ophthalmology

Antibiotikaresistens er i ferd med å bli en alvorlig global helsetrussel. Etter hvert som bakterier utvikler motstand mot dagens medisiner, blir infeksjoner som tidligere var enkle å behandle, igjen livstruende. 
Verdens helseorganisasjon (WHO) har laget en liste over farlige bakterier hvor behovet for nye antibiotika er akutt. Dessverre er de fleste antibiotika som utvikles i dag bare små endringer av gamle medisiner – og bakteriene lærer raskt å stå imot disse også.

For å løse dette problemet må vi finne helt nye måter å angripe bakteriene på. Det betyr at vi må oppdage nye angrepsmål i bakteriene og utvikle antibiotika som kan nå frem til og slå ut disse.

Dette prosjektet har som mål å gjøre nettopp det. Et internasjonalt team av forskere samarbeider for å:

Undersøke to spesifikke bakterieenzymer for å se om de kan være gode angrepsmål for fremtidige antibiotika.
Bidra til å øke vår forståelse av hvordan antibiotiske legemidler kommer seg inn i bakteier, noe som er en av de største utfordringene i utviklingen av nye antibiotika.
Vi fokuserer på tre typer skadelige bakterier: Pseudomonas aeruginosa, Escherichia coli og Klebsiella pneumoniae. Disse er alle såkalte «Gram-negative» bakterier, som er spesielt vanskelige å behandle på grunn av deres oppbygning.

I prosjektet vil vi studere to viktige enzymer som disse bakteriene bruker til å lage fettsyrer – molekyler de trenger for å overleve. Ved bruk av ulike teknikker skal vi designe og teste nye inhibitorer som kan blokkere disse enzymene. Samtidig skal vi undersøke hvordan disse inhibitorene kommer seg inn i bakteriene, slik at vi er sikre på at de faktisk når frem til målet sitt.

Ved å kombinere kjemi, biologi og legemiddeldesign vil dette prosjektet ikke bare hjelpe oss med å komme videre på veien til å finne nye antibiotika – det vil også gi verdifull innsikt i hvordan vi kan utvikle bedre antibiotika i fremtiden.

There is an urgent need for new antibiotics to prevent the looming crisis of antimicrobial resistance and WHO has published a list of bacteria for which antibiotics are in high demand and urged that research and drug discovery efforts are directed toward these. Antibiotics are a prerequisite for modern medicine, however, most of the compounds in clinical development are not fit for purpose at they are derivatives of already known antibiotics and therefore have cross-resistance with existing agents.
To tackle this crisis, we need fundamental knowledge on new targets for antibiotics, and we need compounds that can get into bacteria and work on these targets. This project will address this 1) by delivering potent inhibitors on two proposed bacterial protein targets to establish if they are promising targets for future antibiotics and 2) by establishing relationships between compound properties and uptake in bacteria. To reach these highly ambitious goals, we have assembled an interdisciplinary and international team of experts in antibiotic drug discovery, protein dynamics, structure-based drug design, covalent enzyme inhibition, organic synthesis and medicinal chemistry. We will explore two essential enzymes involved in fatty acid synthesis in Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, Gram-negative bacteria for which WHO has stated that new antibiotics are critically needed. We will use a structure-based approach to develop potent inhibitors for chemical target validation. This process will be guided by experimental data about uptake into bacteria to ensure that our compounds reach their targets, a critical step in chemical target validation. Through this we will provide crucial information to advance our understanding of the compound properties that governs uptake in Gram-negative bacteria. This will deliver far-reaching insights, not only for the studied target but antibiotic drug discovery in general.

Validating fatty acid synthesis enzymes as targets for antibiotics against Pseudomonas aeruginosa and other Gram-negative bacteria.

Dette prosjektet har som mål å undersøke nervedannelse i primær brystkreft og hjernemetastaser fra brystkreft. Vår hypotese er at en undergruppe av aggressive brystkreftsvulster involverer nervestrukturer for å fremme tumorprogresjon, inkludert metastaser til hjernevev, som er den mest nevrogene nisjen i kroppen.

Hos kvinner er brystkreft den hyppigste kreftsykdommen og den ledende årsaken til kreftrelaterte dødsfall verden over. Trippel-negativ eller basaloid brystkreft er de mest utfordrende subgruppene, på grunn av mangel på effektive behandlingsmål. Studier av nervefiber-tetthet i brystkreft har vist at høyt innerverte svulster er mer aggressive, og tilstedeværelse av nerve-elementer er assosiert med økt metastasering og forverret pasientprognose. Våre foreløpige data, fra vevsanalyse av to brystkreftserier, bekrefter disse funnene. Vi anser derfor nerveinvolvering som en ny og lovende biomarkør i vår forståelse av aggressiv brystkreft.

Nerver er små fiber-strukturer i svulster, som nåler i en høystakk, og vanskelig å oppdage ved vanlig mikroskopisk undersøkelse. Derfor eksisterer det ikke automatiserte prosedyrer for deteksjon av slike svulst-nerver, og nervene sin klinisk-patologiske betydning er lite kjent. I dette prosjektet vil vi utvikle mer sensitive metoder for å påvise små nerveelementer i vev fra svulster, ved hjelp av avansert bildeteknologi. Interaksjon mellom kreftceller og nerver vil bli analysert i funksjonelle studier.

Vår hypotese er at aggressive brystkreftceller utrykker hittil ukjente markører som kontrollerer tiltrekning av nerver til primærsvulsten, og at denne tiltrekningen forårsaker endringer i en undergruppe av brystkreftceller som fremmer spredning til hjernen.

Recent data indicate that nerves might play an active role in the initiation and progress of cancer. In the breast, research by us and others has demonstrated that enhanced innervation is associated with more aggressive tumors, such as the triple negative subtype (TNBC) supporting the formation of a neurogenic niche in primary tumors. However, the detailed clinical relevance of this phenomenon, and the mechanisms by which nerves are attracted to breast tumors and how breast cancer-nerve interaction promotes aggressive tumor features, remain unexplored. Moreover, we lack good experimental models for breast cancer innervation in a human setting. 

TNBCs with a basal-like phenotype are also prone to metastasize to the brain, the most neurogenic niche in the body, but the preference for the brain as a metastatic site is not understood, neither are the phenotypic alterations that breast cancer cells undergo in brain tissue. Here, we launch a new concept - epithelial-to-neural transition (ENT) – linking cancer cell plasticity and nerve involvement in primary and brain metastatic breast cancer. We suggest that aggressive breast cancer cells express yet unknown markers that control attraction of nerves at the primary site, and that some breast cancer cells even transform by acquiring neural-like properties and spread to the brain. Epithelial-to-neural transition will be investigated both clinically and experimentally in primary and brain metastatic breast cancer by combining large clinical cohorts, spatial omics technology, and stem cell methods to establish cutting-edge models. 

This project has the potential to change the way we view neural elements in breast cancer and provide the field with new clinical relevance, models and technologies to study them.

When breast cancer hits a nerve
- Neural involvement as a hallmark of tumor progression

Immunforsvaret vårt gir oss et naturlig forsvar mot kreftutvikling. Naturlige dreperceller, også kalt Natural Killer (NK) celler, er en del av immunforsvaret og er spesialiserte på å søke ut og tilintetgjøre kreftceller. Kreftceller kan unngå immunforsvaret, og vil når det skjer vokse til en svulst. NK-cellene er ikke gode til å trenge inn i svulsten, og kan dermed ikke ta livet av kreftcellene. NK-cellenes våpen er giftstoffer som sprøytes inn i kreftcellene når de får direkte kontakt. I tillegg kan NK-cellene produsere små missiler som inneholder gift. Disse missilene slippes vanligvis løs når NK-cellene møter en kreftcelle. På laboratoriet kan vi dyrke NK-celler, og få dem til å slippe ut missilene sine. Vi samler opp missilene, og kan så bruke disse til å drepe kreftcellene. Missilene er veldig små, og har bedre evne til å trenge inn i en svulst. Med dette prosjektet ønsker vi å forstå hvordan missilene lages i NK-cellene, og å bedre forstå hvordan de søker opp og dreper kreftcellene. Vi håper at vi med dette prosjektet vil legge grunnlaget for en fremtidig kreftterapi.

With this project, we will build the basis for developing NK-cell derived extracellular vesicles (NK-EVs) as a new cancer therapeutics. NK cells and CAR-NK cells are already being exploited in therapies against hematological malignancies and solid tumors. With NK-EVs we will leverage on the combined power of the killing capacity of NK cells with that of the advantageous aspects of EVs as natural carriers of biomolecules and tissue penetration. We and others have demonstrated that NK-EVs induce apoptosis of a wide range of cancer cells in vitro, and a few studies have also shown efficacy in vivo. EVs are emerging as a new therapeutic avenue in several disease contexts, but the field needs to address and solve critical bottlenecks to allow their exploitation. This proposal will address two major knowledge needs, which is 1) to determine the mechanism of action of NK-EVs, and 2) to understand the heterogeneity of the NK-EV secretome to define the EV subset inducing cytotoxicity. To address these needs, we will perform CRISPR screens in two cancer cell lines to discover proteins that are necessary for mediating the effects of NK-EVs, further we will define the precise mechanism of action of how NK-EVs deliver their cytolytic cargo, and finally utilize single-EV technologies to dissect the EV secretome form NK cells released under different stimulatory conditions. Results from this study will be used to design production protocols and relevant potency assays which is a prerequisite for developing NK-EVs into a therapeutic product.

Cytotoxic activity of NK cell-derived extracellular vesicles against cancer cells.

Økonomisk ulikhet øker i Norge og andre høyinntektsland, mens innvandring også er med å endre samfunnets demografiske og sosioøkonomiske struktur. I kjølevannet av økende økonomiske og etniske forskjeller, er det bekymringsfullt at ulike dimensjoner av ulikhet blir stadig mer vedvarende på tvers av generasjoner. Å fremskaffe kunnskap om i hvilken grad ulikhet overføres innenfor familier og bredere sosial kontekster, vil kunne si noe om hvilke muligheter man har senere i livet. Til tross for mye forskning på intergenerasjonell mobilitet for utdanning og arbeid, har det vært lite forskning på betydningen av helse i overføringen av sosioøkonomisk status fra foreldre til barn.  
I  HEALTHMOBILITY ønsker vi å studere (1) i hvilken grad helsestatus overføres gjennom generasjoner og sammenhengen mellom helse og sosioøkonomisk mobilitet, (2) den kausale effekten av helseforskjeller tidlig i livet og i ungdomsårene på voksne prestasjoner og sosial ekskludering, (3) i hvilken grad de ovennevnte prosessene varierer mellom barn av innvandrerforeldre og de uten innvandringsbakgrunn, og, (4) hvordan forholdet mellom sosioøkonomisk status og helse har utviklet seg historisk—ved å studere langsiktige trender som strekker seg over mer enn 50 år. Prosjektets bidrag vil være å undersøke betydningen av både foreldre og barns helse som en dimensjon av intergenerasjonell mobilitet, sosial ekskludering, og livsjanser gjennom generasjoner.

Economic inequality is on the rise in Norway and other high-income countries, while large-scale immigration is also changing the demographic and socioeconomic structure of these societies. In the wake of widening economic disparities and ethnic inequality, there is growing concern among social scientists and policy makers that various dimensions of inequality are becoming increasingly persistent across generations. Knowing to what extent inequality is perpetuated within families and within broader social contexts is crucial since most would agree that opportunities in life should not be determined by which family a child is born into. Despite a vast literature on intergenerational mobility and children’s prospects for moving up the socioeconomic ladder, there is little research on the intergenerational transmission of health status and its role in the transmission of socioeconomic status from parents to children. This is unfortunate, as health is increasingly acknowledged as an essential part of individuals’ human capital, with important consequences for individuals outcomes in education and the labor market. 
In HEALTHMOBILITY we aim to study to what extent (1) health status is passed down through generations and its relation to socioeconomic mobility, (2) the causal impact of early-life health disparities on adult attainments, (3) to what extent these processes vary between children of immigrant and native parents, and (4) how the relationship between socioeconomic status and health status have evolved historically. Our aim is to unpack how mechanisms related to intergenerational transmission of health inequality contributes to socioeconomic and ethnic disparities in educational and labor market attainments. We will use Norwegian data from population-wide administrative registers and large-scale surveys, with detailed information on health service use, self-reported measures of health, and key socioeconomic and demographic characteristics to address these issues

Socioeconomic and Ethnic Inequality in Health and Intergenerational Mobility (HEALTHMOBILITY)

Antimikrobiell resistens (AMR) er en alvorlig trussel mot folkehelsa som er spådd å bli verre i fremtiden. En av de vanligste metodene som bakterier bruker for å kunne stå imot antibiotika, er å skaffe resistensgener. Disse sitter ofte på noen DNA-deler som heter plasmider. Plasmider som bærer resistensgener er vanligere i kliniske miljøer enn samfunnet ellers, og det å forstå hvorfor vi har denne forskjellen er svært viktig for å forstå hvordan resistente bakterier sprer seg. Men plasmider utvikler seg raskt, og kan spre seg mellom forskjellige bakteriestammer. Derfor er det vanskelig for oss å klassifisere og overvåke dem. I PEAK skal vi benytte oss av nye sekvenseringsteknologier og utvikle nye metoder for å forske på hvordan plasmider utvikler seg og sprer seg, med fokus på den viktige sykdomsfremkallende bakterien Klebsiella pneumoniae. Vi skal utvikle nye metoder for å klassifisere plasmider og analysere de genetiske forskjellene mellom plasmidgrupper. Deretter skal vi bruke disse plasmidgruppene til å forske på hvordan plasmider sprer seg mellom forskjellige miljøer og typer Klebsiella. Så skal vi utføre detaljerte analyser av de genetiske endringene som driver utviklingen av plasmider. Målet er å bruke de nye metodene og kunnskapen til å forbedre overvåkning, både av AMR Klebsiella pneumoniae og andre bakteriestammer.

Antimicrobial resistance (AMR) is a global threat to human health which is predicted to increase in the future. One of the most common ways that bacteria evolve resistance to antibiotics is by acquiring AMR genes; these are often carried on small pieces of DNA called plasmids. Understanding the mechanisms and conditions that promote AMR dissemination via plasmids is critical, but several knowledge gaps remain. AMR is unevenly distributed among environments, whilst the highest levels of AMR are typically found in clinical environments, the risk of AMR acquisition from environmental and animal settings remains less clear. Plasmids are important vectors for the transmission of AMR between environments, but plasmid evolution is complex, and lack of appropriate data and methods has to date largely precluded high-resolution study and surveillance of plasmids in most major pathogens.

In PEAK, we will use two newly generated long-read sequencing datasets to study the evolution and transmission of plasmids and AMR genes in Klebsiella. By combining the datasets, consisting of 1594 isolates from diverse one-health sources, we will establish a unique collection of hybrid assemblies, including thousands of complete plasmids. Next, we will develop novel methods to quantify the genetic structure and diversity of plasmids. By combining this information with genetic variation in the isolate chromosomes and metadata, we will then perform phylogenetic and association analyses to disentangle AMR distributions among environments. This will enable us to identify high-risk environments for AMR transmission, followed by detailed evolutionary analyses to gain insight into the tempo and mode of plasmid evolution, and how chromosomes coevolve with plasmids.

The overarching aims of PEAK are to uncover the drivers and mechanisms of the acquisition and maintenance of AMR, with the ultimate goal of enabling use of this knowledge to design interventions to combat the spread of AMR in the future.

PEAK: Plasmid Evolution and Antimicrobial resistance in Klebsiella pneumoniae

Verifying the therapeutic potential of newly discovered siRNA drug candidates for treating acute leukemia.

Midlene fra PESORDNING-PESORDNING fordelt på år

Midlene fra PESORDNING-PESORDNING fordelt på fylker

Midlene fra PESORDNING-PESORDNING fordelt på fagområde

Senior Researcher

Gjelder etablering av en søknad rettet mot en utlysning fra EDF-programmet.

Advanced Software defiNEd secuRE Underwater modemS

Catalytic dehydrogenation of NGL is a vital process for the production of olefins. Typically, Cr-oxide or Pt-based catalysts are used for commercial processes. The project focuses on the application of operando and in situ spectroscopic studies of Cr-oxid e based catalysts during dehydrogenation of propane in order to obtain more fundamental insight into the nature of active Cr sites and in the dehydrogenation and deactivation mechanisms. The project involves the use of Diffuse Refelectance UV-Vis Spectros copy (UV-Vis-DRS), combined in situ Raman and FTIR spectroscopy and the TEOM reactor.

Catalytic dehydrogenation of NGL components. Application of in situ spectroscopic techniques for studying dehydrogenation catalysts.

Assume tha a three step one-pot reaction is tt be optimised: 

Lay out a design to map the first step. Depending on how detailed information is desired, this can be a fractional factorial, factoral, D-optimal, or a response surface design for quardratic m odels. Run the experiments and detrmine the responses. The response matrix
Y = [y1 y2...yr] summarises the results. A principal component analysis of Y will determine the number of independent event yielding Y, i.e the number of independent reaction that are responsible for the products (desired product and parasite products). By fitting regression models to the score vectors from the PCA of Y it is possible to identify the variable that are significant  and necessary to control for favouring the dessired  reaction and, equally important, which variable shoul be controlled to suppress the paraste reactions. We can, of course, also use PLS to model the fisrt step and use the PLS(X) scores as extra variables for the second step Now we know the important vari ables for the first step. These are now added as extra design variables when the experimental design for the next step is laid out and we determine the the composition of the reaction mixture after the second step. The outcome of the first step defines th e input for the second step. By perturbing the important variables of the first step we will induce variation in the input for the second step. This is necessary since certain by-products may be detrimental in subsequent steps. By this procedure, we conca tenate teh first and the seciond step of the process. The procedure is iterated for the third (an for all subsequent) step(s).
This technique makes it possible to establish quantitative models for multi-sstep batch pocesses. The model pays attantionto all  possible interfering side-product and gives a possibilty to control the process. This will be important when the TAC regulation is implemented and that pharmaceutial production must account for possible variation i

Design and optimisation in organic synthesis: Methodologies for the optimisation of multi-step one-pot batch processes

The goal of the project is to design new transition-metal complexes with a reactivity that is highly selective for the alkene double bond function. The selectivity will be exploited in the development of functional group tolerant catalysts for an importan t class of olefin refinement process: Olefin metathesis. In this process, catalyst tolerance toward functional groups other than the alkene double bond is vital and reduced activity is observed for the most functional group tolerant catalysts for olefin m etathesis. A second major challenge within olefin metathesis is particularly evident in organic synthesis, where the lack of rational control of the formation of cis and trans olefinic products currently represents a serious drawback. We intend to obtain active and functional group tolerant catalysts for olefin metathesis by a tight integration of theory-driven quantitative structure-activity relationships (QSAR) catalyst design with expertise in organic, inorganic and organometallic synthesis as well as catalysis. Target structures based on the mid and late transition metals will be generated by the QSAR prediction-approach and subsequently subjected to synthesis and testing of catalytic activity. Finally, complexes active for olefin metathesis will be i nvestigated for possible optimization of stereoselectivity.

Theory-assisted design of functional group-tolerant catalysts for olefin conversion

Acid catalysis over zeotype materials is one of the most important and fundamental topics in catalysis. Basic natural gas conversion processes like MTO (methanol to olefins), dimerisation, and C4 isomerisation can be performed using acid catalysis by zeol ites and/or microporous SAPOs. In addition, refinery processes like catalytic cracking, reforming, aromatisation and C5-C6 isomerisation rely on zeotype catalysts as well. There is a growing understanding that many of these reactions share common features  regarding the elementary reaction mechanisms including deactivation.

The Oslo group has a long history of research on MTH-type reactions, and a break-through in the understanding of  the reaction mechanism has come during the past few years. In this pro ject, our ambition is to bring this knowledge even further  by studying the effect of individual material parameters on the selectivity of MTH-type reactions. Electronic effects, steric requirements as well as diffusion effects are among the main paramete rs affecting the reactions and they have previously not been studied in much detail.

Although MTH-type reactions are the focal point of this project, we believe that the results of the project will be beneficial not only for the creation of a second gene ration MTH catalyst, but also for tailoring catalytic zeotype materials for other carbocation-mediated reactions.

Carbocation mediated hydrocarbon reactions over acidic zeotype catalysts

Katalysesymposiet er Faggruppa for katalyse (Norsk kjemisk selskap) sitt viktigste arrangement. Faggruppas medlemmer er spredt over hele Norge, og samles bare til årsmøtet og katalysesymposiet som dermed får en viktig nasjonal faglig funksjon. Symposiet f ungerer tradisjonelt også som årsmøte for katalysedelen av forskningsprogrammet KOSK (Katalyse og Organisk Syntetisk Kjemi) i Norges Forskningsråd. 
Hovedhensiktene med symposiet er å vise bredden i norsk katalyseforskning, samt å gi yngre forskere en mul ighet til å fremvise og dikutere sine resultater. Årets symposium vil bli avholdt over to dager, 23. og 24. oktober i Forskningsparkens lokaler i Oslo. Årets inviterte plenarforedragsholder vil være Professor J. A. Moulijn fra det Tekniske Universitetet i  Delft, Nederland.


Norsk Katalysesymposium 23.-24. oktober 2007

The main physiological role of the human G-protein coupled chemokine receptor CXCR4 and its natural ligand SDF-1a is homing of leukocytes and embryonic development. However, CXCR4 has also been shown to be involved in the pathology of several serious dise ases, most notably AIDS (HIV entry point in T-cells) and cancer (angiogenesis and metastasis). Consequently, CXCR4 antagonists have emerged as a promising class of drugs. The primary objective of this project is to establish the structure-activity relatio nship and binding mode for cyclopentapeptide CXCR4 antagonists in order to facilitate the future design and synthesis of novel peptidomimetic CXCR4 antagonists with therapeutic potential. 

As for most other GPCRs, the experimental structure of the human  CXCR4 receptor has not been elucidated. In the absence of target structure, rational development of novel antagonists relies on ligand-based design, i.e. the information obtained from active and inactive ligands in structure-activity studies. Accordingly,  the foundation of this project is the design and synthesis of semi-rigid cyclopentapeptide ligands that will be tested for affinity for wild-type CXCR4 and designed CXCR4-mutants in order to deduce the structural properties of the complementary CXCR4 bin ding site. The experimental data combined with computational studies (pharmacophore modeling, homology modeling and docking) is expected to result in detailed insight into the structure-activity relationship and binding mode of cyclopentapeptide ligands.  This information will in turn facilitate rational development of novel peptidomimetic CXCR4 antagonists with therapeutic potential.

Structure-Activity Relationship and Binding Mode for Cyclopentapeptide Antagonists of CXCR4, a Therapeutic Target in HIV/AIDS and Oncology

The next Organic Winter Meeting, the 24rd, will take place January 8th-11th 2009 at Thon Hotel Skeikampen, Skeikampen. This conference is the national meeting in organic chemistry in Norway, and it is held under the umbrella of the Division of Organic Che mistry of the Norwegian Chemical Society. Master and Ph.D.-students as well as pod.doc.-fellows present research results from their projects at the meeting. Four distinguished chemists have been invited and have accepted to participate as plenary speakers . The OKV-24 meeting will emphasize on these following topics: 
organometallic chemistry; natural products synthesis; medicinal chemistry; organocatalysis/asymmetric synthesis and synthetic methodology while keeping particular emphasis on bio-organic aspe cts.

Organic Chemistry Wintermeeting 2009

Adenosine is a signaling substance, which mediate its effects by activation of fours different G-protein-coupled receptors (GPCR) (A1, A2A, A2B and A3). The receptors differs in their affinity for adenosine as well as their downstream signaling pathways a ctivated in the target cells. The ARs are present in basically every cell in the body, but their abundance in different tissue varies. Adenosine has very limited applications as a drug due to an extremely short half-life (t1/2 < 10 s). Caffeine and theoph ylline are classical non-selective AR antagonist with high affinities for A1 and A2A receptors. The excitatory effects of caffeine are a result of its ability to antagonize adenosine activity at A1 receptors in the central nervous system. A selective and  potent ligand for any of the ARs may have a drug potential, i.e. A1 antagonists for treatment of asthma, A2A antagonists as anti-Parkinson drugs, A2B antagonists for treatment of chronic pulmonary diseases and A3 antagonists as anti-cancer agents. We have  recently initiated screening of a small library of 6-arylpurines examined by us earlier as selective inhibitors of Mycobacterium tuberculosis. From the results currently available, it is clear that minor structural changes may lead to compounds with comp letely altered selectivity, and we believe, that potent and selective antagonists of all four AR sub-types will be synthesized in the planned project. Synthesis of optimized structures with respect to potency and AR sub-type selectivity will be carried ou t at the University of Oslo, and target compounds will be designed based on available screening results, molecular modeling and drug-like physiochemical properties. Biological evaluations as adenosine receptor ligands in the group of Prof. Christa Müller,  University of Bonn and molecular modeling may be conducted in cooperation with Prof. Müller and collaborators at the University of Bonn and the Fraunhofer Inst. St. Augustin.

Design, synthesis and biological evaluation of selective antagonists for the various adenosine receptors

With the advent of drug design, high throughput screening and combinatorial chemistry, medicinal chemists became less and less interested in natural products as a source for drugs. In the last two decades, medicinal chemists seemed inclined towards the ap parently more accessible synthetic products obtained from combinatorial chemistry. However, it has been recognized that combinatorial chemistry has severe limitations in generating novel classes of biologically active compounds, as seen by the sharp decli ne of number of approved drugs the last ten years. 

In this research proposal we will prepare two polyunsaturated marine natural products, bacillariolide I and zonariaenon, from eicosapentaenoic acid. These two natural products, as well as some of the in termediates, will be submitted to molecular modeling and biological testing as potential antagonists or agonists for the peroxisome proliferating activating delta receptor.

The ethyl ester of eicosapentaenoic is produced in Sandefjord, Norway by the Norw egian pharmaceutical company Pronova.  Pronova is establishing a synthetic group in Oslo. In the near future Pronova must need synthetic chemists with competence and a strong background in handling air and light sensitive polyunsaturated fatty acids, as w ell as their derivatives. This project will gain knowledge in how to handle and use eicosapentaenoic acid as a starting material in organic synthesis.

Moreover, the natural products prepared in this research proposal may aid the elucidation of the physio logical role of the peroxisome proliferator-activated receptors. With full knowledge of these receptors and their physiological role, control of a number of maladies, such as type 2 diabetes, obesity and cardiovascular disease may be possible.

Synthesis of two polyunsaturated natural products using epa as starting material

The Organic Winter Meeting is the national meeting in organic chemistry in Norway. It is a conference under the umbrella of the Norwegian Chemical Society, which has given me the task to organize the meeting. 

Since its infancy the tradition has been to invite 3-4 eminent chemists, covering various subdiciplines of organic chemistry, to give the plenary lectures. Due to financial support from the research council over the years it has been possible to maintain this tradition without having to charge a co nsiderable conference fee. This has been absolutely instrumental to keep up the numbers of participants in times with little money at Norwegian universities for conference participation.

The next winter meeting, which I will organize, will take place fro m the 10th to the 13th of January 2008. The participants will arrive with train midday the 10th. The meeting will then start just after lunch with a plenary lecture followed by shorter talks, poster presentations etc until approximately 19.30. The schedul e will be almost the same the 11th. The 12th, however, there will be two plenary lectures, and at the very end the annual meeting of the Organic Division of the Norwegian Chemical Society will be held; otherwise, the program will contain shorter talks and  poster presentations as the previous days. The participants will leave with train the next morning.

I have organized the winter meeting three times before, and each time emphasized certain parts of organic chemistry. This time I want to focus on organic  synthesis, in particular bio-organic chemistry.

I have started the process to invite the following as plenary speakers, of whom the three first on the list have accepted the invitation:

Professor Anita R. Maguire, University College Cork, Cork, Ireland 

Professor Dieter Schinzer,University of Magdeburg, Magdeburg, Germany

Professor Peter Seeberger, ETH, Zürich, Switzerland

Professor Snorri T. Sigurdsson, University of Iceland, Reykjavik, Iceland

Det 23. Organisk-Kjemisk Vintermøte 2008

The present proposal describes a novel way of utilising the internal electrical resistance in carbon composite materials to activate catalyst materials for chemical reactions: A compact, internally heated, catalytic reactor is demonstrated for the low-tem perature oxidation of carbon monoxide. Carbon nanofibres were grown on carbon felt and used as a support material for Au/TiO2 catalysts. The carbon composite plays two roles; as a support material for the catalyst and for providing heat to the reaction by  the Joule effect. The internal heating offers a stable reactor system with quick temperature response at relatively low energy input. Comparison between external and internal heating shows higher conversion of CO in the low-temperature range when using i nternal heating.

The project seeks to prepare and compare two kinds of microstructured reactors for small-scale preferential oxidation of CO:
1. Carbon nanofibres grown on carbon felt and used as a support material for Au-Pt/TiO2 catalysts with internal heating
2. Carbon nanofibres grown inside ceramic monoliths to increase the surface area. Also in this case the Au-Pt/TiO2 catalysts will be deposited on to the carbon nanofibres.

PESORDNING-PESORDNING

Advanced Software defiNEd secuRE Underwater modemS

Awarded: NOK 0.55 mill.

Summary

Funding scheme:

PESORDNING-PESORDNING

Funding Sources

Thematic Areas and Topics