2004

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Banebrytende forskning

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Samisk samfunn og kultur

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Demokrati og global utvikling

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Velferd og utdanning

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Helse

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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.

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Om Prosjektbanken

2021

Helse- og omsorgsdep

Matematikk og naturvitenskap

Oslo

Helseforetak

Portefølje Helse

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Koordinerings- og støtteaktivitet

Limb wounds in horses are common, however healing is exceedingly slow and fraught with complications. Contrary to body wounds, limb wounds demonstrate only a small amount of wound contraction. The specialist procedure of applying split-thickness skin grafts to limb wounds stimulates wound contraction by unknown mechanisms. The objective of this project is to identify those mechanisms to develop a treatment strategy for equine limb wounds for use in general  practice. Limb wounds are severely impacting animal welfare due to an extended healing/treatment duration, and the risk of euthanasia due to a poor functional outcome. By stimulating wound contraction, healing time will be reduced, and the functional outcome improved, directly benefitting the welfare of wounded horse and reducing treatment cost for the owner. Aim: To identify dermal components stimulating wound contraction, and to develop this knowledge into future state-of-the-art treatment of equine limb wounds for use in general practice. Hypotheses: i) Application of dermal fractions to collagen gels seeded with equine fibroblasts will increase gel contraction in vitro; ii) Application of dermal fractions to experimental limb wounds in vivo, will increase wound contraction resulting in a faster healing time versus wounds treated by conventional methods. Methods: i) The contractile effect of different dermal components will be assessed in a collagen gel/ fibroblast model; ii) Identified dermal components will be tested in a standardized experimental limb wound model in vivo (n=5). Ultimately, results from this project are expected to improve wound treatment in horses, directly impacting animal welfare by reducing healing time and improving the functional outcome of wounded horses. This will also directly benefit horse owners and caretakers and making veterinarians able to offer better treatment solutions.

HESTEFORSK - Raskere og bedre sårheling hos hest med autologe hudkomponenter

The goal of the Bilingual Experiences, Cognitive Ageing and underlying Mechanisms (BECAME) project is to examine the functional neuroplastic mechanisms underlying mitigatory effects of bilingual experience on age-related cognitive decline. While evidence is available for structural brain changes supporting bilingualism-induced effects on cognitive aging (CA), functional mechanisms underlying such effects are not yet well understood. BECAME aims to fill this gap by investigating the trajectory of bilingualism-induced functional neuroplasticity across the adult lifespan (ages 18-85), crucially adopting an individual differences approach related to measurable degree of bilingual engagement. Importantly, although such benefits are thought to be rooted early in the lifespan, evidence for the timeframe and conditions of their early emergence is scarce. The choice of including the whole adult lifespan allows us to investigate these mechanisms and their emergence more directly from a lifespan perspective. I combine behavioral testing with brain recordings via electroencephalography (EEG). EEG is widely used in cognitive neuroscience to assess brain activity and the degree of communication between brain regions (functional connectivity) in response to stimuli and at rest. Combining behavioral and EEG modalities will allow me to test bilingualism’s effect on functional connectivity, as well as its consequences for functional efficiency, the minimum required neural activation to successfully perform a task. This will enable a detailed, evidence-based account of the protective effects observed in older-aged bilinguals, and how they are built from earlier life stages. By illuminating the relationship between multilingualism and resulting neurocognitive adaptations, BECAME will enable to capitalize on it as a health initiative, with manifold societal implications and the potential to be translated into actionable policies exploiting multilingualism to ameliorate effects of CA.

Bilingual Experiences, Cognitive Ageing and underlying Mechanisms

Hovedmålet med kreftbehandling er å eliminere kreftceller og dette er tradisjonelt oppnådd ved kirurgi, bruk av giftige medikamenter (cellegift) og stråling. En ny og betydningsfull tilnærming til kreftbehandling kalt immunterapi, har derimot fått mye oppmerksomhet det siste tiåret; Her forsøker leger og forskere å utnytte immunsystemet vårt for å målrettet  ødelegge kreftceller. En nøkkelaktør i denne banebrytende tilnærmingen er en gruppe «drapsmenn» i immunsystemet kjent som cytotoxiske T-lymfocytter (CTL-er). Disse cellene har en bemerkelsesverdig evne til å oppdage kreftceller ved å gjenkjenne unormale molekyler på overflaten av kreftcellene - molekyler som friske celler ikke har. Når CTL-er gjenkjenner kreftcellene ødelegger de dem ved å frigjøre giftige molekyler som initierer kreftcellenes selvdestruksjon. 
 
Selv om betydelige innsats har blitt dedikert til å forstå hvordan CTL-er aktiveres og hvordan de gjenkjenner kreftceller, vet vi mindre om de påfølgende hendelsene inne i kreftcellene som fører til deres død. Fra før vet vi at CTL-er kan initiere to forskjellige typer celledød i kreft: den første, kalt apoptose, er en stille og ordnet prosess der kreftcellene krymper og brytes opp uten å varsle immunsystemet; den andre, kalt pyroptose, er en mer dramatisk prosess som involverer dannelse av åpninger i cellemembranen, noe som fører til at cellene svulmer opp og sprekker. Under denne cellebristen blir innholdet inne i cellene frigitt i omgivelsene, og dette kan fungere som 'faretegn' som kan stimulere en sterkere immunrespons mot kreftcellene. Betydningen av denne cellebristen for å forsterke anti-tumorresponsene vil bli undersøkt i dette prosjektet. 
 
Videre er vi fascinert av muligheten for å avdekke ytterligere, ennå ukjente, former for celledød indusert av CTL-er. Utforsking av disse dødsrelaterte prosessene i kreftcellene kan potensielt øke effektiviteten av immunterapi og bidra betydelig i den pågående kampen mot kreft.

The primary goal of most cancer therapies is to induce cancer cell death. Immunotherapy relies on the cytotoxic activity of lymphocytes such as natural killer cells (NKs) and cytotoxic T lymphocytes (CTLs) to achieve this. While a significant amount of research in immunotherapy focuses on the events within cytotoxic lymphocytes or at the interface between cytotoxic lymphocytes and cancer cells, less is known about the molecular mechanisms that orchestrate cancer cell death, particularly in the case of CTL-mediated death.
CTLs are known to induce two types of cell death in cancer: non-inflammatory apoptosis and proinflammatory pyroptosis. Pyroptotic cancer cells release proinflammatory signals that attract immune cells to the tumor site, thereby enhancing the anti-tumor response. Cell lysis is a common outcome of pyroptotic cell death. It is unclear whether lysis can be decoupled from pyroptosis in cancer cells and whether the proinflammatory properties of pyroptotic cancer cell death depend on lysis. Moreover, it remains unknown whether CTLs can induce other forms of cell death in cancer, apart from apoptosis and pyroptosis.
Studying the mechanisms of CTL-mediated cancer cell death is challenging because CTLs selectively target cells expressing specific antigens. However, given the critical role of CTLs in immunotherapy, it is essential to deepen our understanding of CTL-induced cancer cell death.
This project aims to develop novel methodologies to investigate the death mechanisms that are initiated by CTLs. In addition, we will identify new pathways and mediators involved in CTL-induced cancer cell death. Furthermore, we will assess the contribution of proinflammatory cell death and lysis in promoting anti-tumor responses in vivo. Overall, this research will improve our knowledge of the molecular mechanisms of CTL-mediated cancer cell death and potentially reveal novel targets to enhance the efficacy of cancer immunotherapy.

T-cell-mediated proinflammatory cell death and lysis in cancer

En av de vanligste, men minst studerte, utfordringene med å bli eldre er problemer med å kommunisere. Mange eldre sliter spesielt med pragmatiske ferdigheter, som å forstå undertekst, eller tilpasse det de sier til personen de snakker med. 

La oss si at en lege må gi en alvorlig beskjed til en pasient. For å gjøre det litt lettere å takle, bruker legen vagere språk, som "kanskje" i stedet for "sannsynligvis". Mens yngre voksne ofte tar hensyn til høflighetsstrategier i måten de tolker det som blir sagt på, har eldre ofte vanskelig for å forstå når noen snakker indirekte. Mange eldre voksne har vanskelig for å forstå ikke-bokstavelig språk og kan misforstå alvorlighetsgraden av diagnosen. Dette kan påvirke beslutningen deres om behandling, noe som kan føre til utilsiktede konsekvenser. 

Siden god kommunikasjon er viktig både i viktige medisinske samtaler og i hverdagen, er det viktig at vi finner ut hva som gjør at eldre kan ha vansker med å forstå og bli forstått. RESILIENCE skal hjelpe til med denne utfordringen ved å samle data om praktiske, kognitive og språklige ferdigheter hos voksne i alderen 18-90 år over tid. Dette vil gi oss en stor mengde data om pragmatiske, kognitive og språk ferdigheter og gjøre det tilgjengelig for forskning. Med denne dataen som grunnlag har vi følgende mål: 

• Forstå hvordan praktiske evner endrer seg generelt gjennom voksenlivet. 
• Finne ut hvilke mekanismer som påvirker pragmatiske evner på forskjellige tidspunkter i livet.
 • Utvikle en teoretisk modell som forklarer hvordan pragmatiske ferdigheter endrer seg med alderen.
 • Lage algoritmer som kan forutsi hvordan pragmatiske evner vil utvikle seg for enkeltpersoner i årene som kommer. 
• Utvikle og teste et verktøy som kan måle pragmatisk helse (både pragmatiske ferdigheter og deres underliggende mekanismer), noe som kan åpne  for å iverksette tiltak. 

Dette vil gi oss muligheten til å forstå bedre hvordan folk kan utvikle pragmatisk resiliens gjennom livsløpet.

A cornerstone of human communication is our reliance on pragmatic skills to guide linguistic interactions (e.g., reasoning about others' mental states to bridge the gap between what is said and intended in conversation). However these skills are highly sensitive to age-related decline, leading to miscommunication and uninformed decision making in the older adult population. This raises an important question, one which has puzzled linguistics and psychologists for decades: if pragmatic competence is fundamental to communication, why do individuals vary so much in this capacity? 

Traditionally, psychologists have approached pragmatic competence from a cognitive angle, reasoning that individual differences in executive functions (i.e., the cognitive skills associated with goal-directed actions) are what underlie effective pragmatic behavior. In a similar vein, language scientists have taken a linguistic approach, reasoning that one’s language background (e.g., the frequency with which individuals shift between languages) shapes pragmatic skills by enhancing sensitivity to the communicative context. This focus on either cognitive or linguistic influences has resulted in two expansive yet disparate areas of research.

RESILIENCE will unite these disciplines to pursue a longstanding debate on what underlies pragmatic resilience and decline using a large-scale, interdisciplinary and longitudinal approach. By gathering data on adults' (ages 18-90) pragmatic, cognitive and language skills over multiple time points, we will develop a comprehensive theoretical model that explains how cognitive and linguistic systems interact to shape pragmatic competence as we age, and create algorithms that predict the trajectory of an individual’s pragmatic abilities in upcoming years. Based on these results we will design a multidimensional tool that detects the earliest signs of pragmatic deficits, leading to future interventions, allowing us to uncover the paths to pragmatic resilience.

Uncovering the paths to pragmatic resilience

Sink er et essensielt mikronæringsstoff som kreves for funksjonen til hundrevis av proteiner involvert i et bredt spekter av biologiske prosesser. Etter inntak av sink fra kosten reguleres nivåene i kroppen nøye gjennom absorpsjon, sekresjon og ekskresjon via spesialiserte proteiner, såkalte sinktransportører, i tarmen. Enhver ubalanse er skadelig for menneskers helse, spesielt er tarmen følsom for sinkfluktuasjoner, hvilket påvirker tarmbarrieren og kan føre til inflammatoriske sykdommer og kreft i tarmen. 
På molekylært nivå er de presise mekanismene som styrer funksjonen til de ulike sinktransportørene fortsatt uklare. Hos mennesker finnes det over tjue slike proteiner, og de fleste inneholder områder rike på aminosyren histidin. Disse histidinene mistenkes å spille en avgjørende rolle i å binde sink. Nylig oppdaget vi et enzym som modifiserer disse områdene ved å sette metylgrupper på histidin, og viste at metylerte histidiner har en lavere affinitet for sink. Dette prosjektet har som mål å identifisere nye mekanismer som regulerer sinknivåer gjennom histidinmetylering av sinktransportører, å utvikle forskningsverktøy for effektiv studie av histidinmetylering, og å legge grunnlaget for nye behandlinger av tarmsykdommer.

The delicate balance of zinc levels in the body is essential for human health. Zinc is absorbed and excreted via intestinal zinc transporter proteins, and perturbations of this process are associated with pathologies, including inflammatory diseases and cancers of the bowel. The precise molecular mechanisms regulating zinc transport, however, remain a major knowledge gap. Based on the recent discovery of an enzyme methylating histidine residues in zinc transporters, and drawing on preliminary findings which demonstrate reduced affinity of methylated histidines to zinc, this project aims to identify novel mechanisms regulating zinc homeostasis through histidine methylation. We will examine the regulation and effect of histidine methylation on zinc transport in intestinal cell culture and organoids, and examine how knockout of the methylhistidine-generating enzyme affects the integrity and pathology of the intestinal tract in mouse models. In addition, we will identify reader proteins specifically recognizing methylhistidines and develop anti-methylhistidine antibodies and inhibitors to use as tools for detection, enrichment, and inhibition of histidine methylation. Such tools are urgently needed by the international research community, as none are currently available commercially. Overall, this project will lead to great advances in the field of protein regulation, and may uncover novel mechanisms in intestinal zinc transport and pathology.

Zinc transport regulation through histidine methylation

Noen av oss tåler stressende livshendelser godt. Andre derimot utvikler vedvarende fysiske og psykiske plager som følger av stress. Hvor godt vi håndterer stress avhenger av et komplekst samspill mellom miljøfaktorer, sosiale forhold, biologisk sårbarhet og indre motstandskraft. Forskning på stressreaksjonene til dyr og pasientgrupper som til vanlig lever under mye stress viser at en gruppe signalstoffer i kroppen som aktiverer det samme hjernesystemet som cannabis – endocannabinoidene – kan begrense styrken på stressreaksjoner og bidra til at man raskere kommer seg til hektene. I dette prosjektet skal vi undersøke hvordan mestring av stress på kort og lang sikt henger sammen med nivåer av endocannabinoider i kroppen for å forstå hvorfor noen personer er mer motstandsdyktige mot stress enn andre. I den ene studien følger vi pasienter som skal gjennomgå en stressende, men veldig vanlig, situasjon: kirurgi. Her måler vi pasientenes opplevelse av stress, samt mentale og fysiske helse, fra tiden før til to år etter operasjonen og undersøker hvordan dette henger sammen med nivåene deres av endocannabinoider og andre stresshormoner. I den andre studien bruker vi data fra et eksperiment hvor deltakerne har blitt utsatt for psykososialt stress til å undersøke om endocannabinoidnivået deres påvirker hvordan de reagerer på stress, og om stresset i seg selv kan påvirke kroppens produksjon av endocannabinoider. Til syvende og sist er målet med studien å vurdere hvorvidt målinger av endocannabinoidnivåer kan brukes til å forebygge helseplager og til å evaluere behovet for økt oppfølging etter alvorlig stressende påkjenninger i livet.

In the face of major life stressors, some individuals cope well whereas others develop ill health and long-term adverse outcomes. Predicting who needs additional support in response to major life stressors is essential for targeted prevention and more efficient allocation of resources. The endocannabinoid system is emerging as a promising target for understanding vulnerability and resilience to stress. This system appears to buffer stress in two ways: by limiting the magnitude of the stress response, and by facilitating recovery after a stressful event. While the early findings are intriguing, they mainly stem from studies in rodents and small clinical groups with high stress burden. What role endocannabinoids have more globally for human resilience, health and well-being remains elusive. 

In this project we address this gap by leveraging comprehensive experimental and clinical data on two potent stress models: psychosocial stress and surgery. Drawing on these unique datasets, which combine experimental control with ecological validity, we will decipher how endocannabinoid levels influence people’s stress response and recovery across minutes, days, weeks and years. The project represents a novel directional shift for endocannabinoid research and will (i) determine the value of endocannabinoid levels as a biomarker to predict outcomes after surgery, (ii) quantify sex differences, (iii) assess endocannabinoid interplay with opioid analgesics, sex hormones and other stress markers (iv) spearhead open and reproducible science practices in endocannabinoid research, and (v) make this fine-grained and novel data available through an interactive web application. 

This project represents an ambitious effort to understand endocannabinoids’ role in stress resilience and will determine the value of endocannabinoids as a predictive biomarker and potential target for individualized treatment.

Deciphering endocannabinoid stress buffering in humans: 
Mechanistic and clinical investigations

WHeelchair Activity Monitoring project (WHAM)

Wheelchair users (WCU) are three to five times more inactive than the general population, leading to a high risk of developing preventable secondary conditions. Although physical activity (PA) guidelines have been specifically developed for WCU, we lack systematic approaches to implement them in practice, as well as valid algorithms to monitor PA change in WCU through sensor-based solutions. Accordingly, the overall scientific aim of the WHeelchair Activity Monitoring project (WHAM) is to advance PA research and practice in WCU by developing valid digital markers for monitoring of and providing feedback on PA, paving the way for implementation and intervention. I will accomplish this through combining the complementary research fields of 1) behavioural intervention studies focusing on increasing PA in WCU (core competence University of British Columbia, UBC; outgoing phase) and 2) sensor-based PA monitoring (core competence Norwegian University of Science and Technology, NTNU; returning phase – consolidated by non-academic placement at Maastricht Instruments, which develop research prototypes including PA monitors). WHAM’s scientific aim is achieved through three objectives: 1) Measure the effect of a pragmatic exercise intervention trial on self-reported physical activity levels and cardio-respiratory fitness, 2) Develop valid algorithms for tracking PA markers in WCU, and 3) Co-create a framework that outlines how PA can be conjointly monitored and provided feedback on in WCU. This fellowship will enable me to become established as an internationally recognized researcher in the field of “physical activity and disability”, while bringing together ongoing national disjointed research activities in this field. Altogether, my overall ambition is to contribute to reducing inequalities in daily-life participation among WCU compared to the rest of the population.

BOLD MINDS aspires to enhance the understanding of vulnerability factors underlying the emergence of borderline personality disorder (BPD), with an ultimate aim of increasing the potential for young individuals to receive early, evidence-based help when their mental health is at risk. BOLD MINDS will achieve this by investigating whether disruptions in two aspects of autobiographical memory (AM), narrative identity (NI) and involuntary AM (IAM), are associated with BPD features and problem behaviours in adolescents concurrently and over time. In doing so, BOLD MINDS will strengthen the understanding of mechanisms underlying the emergence of BPD in adolescence and lay a groundwork for developing evidence-based early interventions for BPD. While currently limited, the study of AM in this field is essential for two reasons. Firstly, because the aspects of AM under investigation, NI and IAM, are known to be involved in identity formation and emotion regulation which represent two key psychological processes that are disrupted in adults with BPD and are linked to problem behaviours such as self-harm and suicidality. Secondly, because promising research is emerging on the use of AM targets in the treatment of emotional disorder in adults, and provides a strong model for future treatment development with vulnerable adolescents. In addition, this timely research program aligns with calls from international organizations to prioritize early interventions to promote adolescent mental health. BOLD MINDS will adopt and adapt state-of-the-art ecological momentary assessment and analytical techniques and work at the crossroads of clinical and cognitive psychological perspectives, allowing for a multidimensional approach to understanding BPD vulnerability. Training-through-research and formalized training of the experienced researcher will prepare her for a permanent academic position and the founding of her own research lab specializing in AM and early interventions for BPD.

Borderline Personality Disorder: Memory and Identity in Adolescence

Per- og polyfluorerte stoffer (PFAS) er en stor gruppe menneskeskapte kjemikalier med høyt fluorinnhold som antas å ha negative helseeffekter. Kilder til PFAS kan være produksjon av vann-, varme- og flekkbestandige produkter og disse kjemikaliene er en del av hverdagen vår. PFAS påvirkning av biologiske systemer er ikke fullstendig forstått. Noen PFAS er antatt å øke risikoen for å utvikling av ikke-alkoholisk fettleversykdom (NAFLD) og øke risikoen for diabetes. 

For å forstå hvordan PFAS påvirker organene våre ønsker vi å bruke små laboratoriedyrkede organmodeller, kalt organoider. Disse miniatyrorganene kan dyrkes fra menneskelige stamceller og tilbyr et kontrollert miljø for å studere hvordan PFAS påvirker f.eks lever og bukspyttkjertelen vår, uten bruk av dyreforsøk.

For å studere helseeffekter må vi kunne måle nivået av biomolekyler som fettstoffer i leveren og hormoner i bukspyttkjertelen. Til dette trenger vi å utvikle analytiske verktøy for å måle effektene. Først vil vi bekrefte at når leverorganoidene eksponeres for enkelte PFAS-forbindelser utvikles det NAFLD-lignende sykdom ved å sammenligne den biokjemiske profilen (proteiner og metabolitter) til organoider av lever med PFAS-eksponerte organoider. Deretter vil vi utvide den analytiske verktøykassen for å undersøke hvilke metabolske veier som påvirkes, og om effekten er den samme i NAFLD-induserte og PFAS-eksponerte organoider. Vi vil også eksponere insulinproduserende bukspyttkjertelorganoider for PFAS for å undersøke effekten av PFAS på hormonproduksjon. Når effektene av PFAS-eksponering på lever- og bukspyttkjertel-organoider er etablert, vil organoidene bli samkultivert i en chip, og effektene av PFAS-eksponering vil bli undersøkt og sammenlignet med individuelle organoider.

Persistent organic pollutants (POPs) are believed to contribute to metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and type 1 diabetes. HE-POP aims to investigate the effects of per- and polyfluoroalkyl compounds (PFAS), a type of POPs), on organ function in a controlled environment.

Organoids are multicellular laboratory-grown miniature organs, that are grown from stem cells. HE-POP will use organoids to examine how PFAS affects our organs and develop cutting-edge bioanalytical tools and methodology to measure these effects using liquid chromatography-mass spectrometry. HE-POP hypothesizes that PFAS negatively affects organ function, as evidenced by changes in hormone and lipid levels characteristic of NAFLD and type 1 diabetes. 

Organoids offer a controlled environment to study the effects of PFAS on the liver and pancreas, without the use of animal models. HE-POP aims to gain evidence of the negative effects of PFAS on organ function through controlled experiments on organoids and aid in understanding the biological mechanisms underlying NAFLD and type 1 diabetes.

HE-POP has fundaments in UN sustainable development goals, specifically #3, #12, and #14/15, seeking an understanding of diseases with worldwide prevalence, and understanding how POPs affect our life and surroundings and help enable the right regulatory actions and replacement chemicals.

HE-POP: Studying the Health Effects of Persistent Organic Pollutants, Using Mass Spectrometry, Organoids, and Organ-On-A-Chip

Dette prosjektet, kalt Hukommelse for musikk, fokuserer på det økende antallet mennesker over hele verden som lever med demens, spesielt Alzheimer's sykdom (AD). AD starter typisk med hukommelsesproblemer og påvirker etter hvert daglige aktiviteter. Aktive musikkintervensjoner, spesielt sang, har vist positive effekter på humør, atferd og livskvalitet for personer med demens, men deres innvirkning på kognisjon er ikke godt forstått. Prosjektet har som mål å fylle dette kunnskapsgapet ved å studere effektene av å lære nye sanger på kognitiv, atferdsmessig og hjernemessig funksjon.

Studien vil omfatte hjemmeboende voksne over 65 år med AD fra Argentina, Østerrike og Norge. Deltakerne vil gjennomgå 5 måneder med intensiv musikalsk opplæring (to ganger i uken) og 5 måneder med minimal opplæring (en gang i måneden) i tilfeldig rekkefølge, med en to måneders pause imellom. Intervensjonene inkluderer å lære nye sanger med en personlig musikklærer. Generell kognisjon vil bli målt ved bruk av Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog), og hukommelse for musikk vil bli vurdert gjennom ulike metoder, inkludert atferdsoppgaver og hjerneaktivitet (EEG). Humør vil også bli evaluert i hver økt.

Målet er å inkludere 113 deltakere for å sikre pålitelig påvisning av meningsfulle effekter. Studien vil utforske hvordan humør og hukommelse for musikk bidrar til endringer i kognitive evner, og om disse effektene varierer basert på faktorer som kjønn, alder, AD-stadium, eller tidligere musikalsk opplæring og generell utdanning. Prosjektet vektlegger samarbeid mellom forskere, tjenesteytere og brukere for å sikre studiens relevans og anvendelighet.

The number of people living with dementia is increasing and is high in low, middle, and high-income countries. Alzheimer’s disease (AD), the most common type of dementia, manifests itself initially with cognitive impairment in memory domains, and later affects all activities of daily living. Active music interventions, particularly singing, can help to improve mood, behaviour problems, and quality of life. Too little is known about their effects on cognition, although some promising studies exist. The M4M project aims to fill this gap by measuring effects of learning new songs on clinical, behavioural and brain functioning. Specifically, M4M aims to examine changes in general cognitive functioning and memory for music in non-musician adults with AD undergoing intensive individual musical training based on singing novel songs, compared to minimal training.
        Home-dwelling adults with AD, 65 years or older, in 3 countries (Argentina, Austria, Norway), will receive 5 months of intensive intervention (2x/week) and 5 months of minimal intervention (1x/month), in random order, with a 2-month break in between. Interventions will entail learning new songs with an individual music teacher. At the end of each intervention period, general cognition will be measured with the Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) by a person who is unaware of the intervention received. Memory for music will be tested with observations, behavioural tasks, and brain responses (EEG). Mood will be assessed in each session. We aim to include 113 participants; this will help us to reliably detect clinically meaningful effects. We will also examine how mood and memory for music lead to changes in cognitive abilities, and whether effects depend on sex, age, AD stage, or previous musical training or general education. M4M will be conducted in close collaboration between academic researchers, service providers, and service users to ensure relevance and applicability.

Memory for Music: Effects of individual intensive musical training based on singing in non-musicians with Alzheimer’s disease

Midlene fra PES-POS-Prosjektetablererstøtte EU fordelt på år

Midlene fra PES-POS-Prosjektetablererstøtte EU fordelt på fylker

Midlene fra PES-POS-Prosjektetablererstøtte EU fordelt på fagområde

Posisjonering i forbindelse med 7. rammeprogram

Explaining the evolution and maintenance of reproductive helping and cooperation in wild animals have challenged both theoreticians and empiricist biologists. The theory of kin-selection have successfully explained the highly cooperative societies of euso cial insects, but has also provided insights into the cooperative breeding exhibited by several vertebrates. Some species have more transient relationships, only cooperating during the breeding season. The common eider (Somateria mollissima) is such a spe cies were about half of the females abandon their young to the care of other females. Many of the brood tending females care for additional young, alone or together with other mothers forming a créche. The creche may be joined by helping females that assi st in defending the young against predators. We wish to use mtDNA sequencing and microsatellite typing to assess whether the cooperating females in a creche are relativesand if brood tending females ad opt related young.                   and if brood ten ding females ad This study will be the first to examine possible kinship between cooperating waterbirds, and one of the first to examine kinship in non-territorial species.

Cooperation during brood rearing; an assessment of the effect of kinship

Circadian clocks play a central role in the adaptation of organisms to their environments. These clocks are found in eukaryotic single-cell and multicellular organisms and even in certain prokaryotes. A central task of these biological clocks involve the  timing of physiological events on a daily and seasonal basis, as for example the onset of sporulation in fungi, sleep/wake activities in animals, hibernation, or flower induction in plants. From studies of model organisms negative feedback loops have eme rged as basic elements of circadian pacemakers. A debated question is whether circadian rhythms are ruled by a single master oscillator or whether there exist multiple autonomous clocks. At Stavanger College we are studying the circadian rhythm of nitrate  reductase (NR) in the model organisms Arabidopsis and Neurospora, where clock mutants are available that have an altered or abolished circadian rhythm. These mutants are ideal study obje cts to address the above question about single or multiple circadia n clocks. In this project we investigate NR gene-transcript and activity rhythms in Arabidopsis and Neurospora clock mutants in order to test whether the NR circadian system represents a s elf-oscillating feedback loop or whether NR oscillations are being  governed by a central clock.

The Central Clock Dogma Contra Multiple Oscillatory Feedback Loops

This study seeks to determine the prevalence, allele diversity, mobility and epidemiology of blaTEM (ampicillin) resistance genes and their hosts in a broad range of clinical and environmental settings. Recent studies suggest that environmental population s of bacteria can be an important reservoir of resistance genes of clinical importance. The usual organism-oriented investigation of bacterial populations cannot easily be applied to understand the ecolo gy of antibiotic resistance since most of the resis tance traits are linked to mobile genetic elements that transcend species barriers and the reproduction behavior of single-celled organisms. The increasing challenge from clinical resistance development does therefore advocate a broader examination of res istance gene reservoirs and also a shift in focus from organism-oriented studies to the investigation of the ecology of the genetic trait its elf as an independent functional unit. This project takes on a broad ecosystem perspective that would significant ly enhance our capability to understand the evolutionary origins, reservoirs, dynamics and host interactions encountered by antibiotic resistance genes in their natural ecosystem. T he ecology of blaTEM genes conferring ampicillin resistance will be deter mined from analysis of a broad range of clinical and environmental samples from Norway and adjacent marine and Arctic areas.

Epidemiology of antibiotic resistance in clinical and envirionmental settings: prevalence, host diversity, and transfer of blaTEM genes

Although the archaeal domain basically possesses a prokaryotic type of cell strueture, the archaebacteria share many molecular features with eukaryotes, in particular the mechanisms for chromosome replication and gene expression. Several homologs of cell. -cycle control (Cdc) proteins, which in eukaryotes have been implicated in the regulation of DNA replication, have been identified in Archaea, implying a similar mechanism of cell-cycle regulation. In addition, the archaeal cell-cycle often includes a sho rt pre--replication period but an extensive post-replicative stage, thus being different from eubacteria while sharing similarities with the eukaryotic cell-cycle pattern. We intend to use Archaeoglobus fulgidus, a hyperthermophilic archaeon growing optim ally at 83oC, for further investigations of the archaeal cell-cycle pattern and its regulation, mapping and analysis of the origin of DNA replication, as well as elucidation of the possible role(s) of the A. fulgidus Cdc homologs in replication initiation. The cell-cycle pattern and replication origin will be analysed and mapped using flow cytometry and marker frequency analyses, respectively. The function of the Cdc proteins will be elucidated using various DNA-binding assays, structural analy ses, and development of an in vitro system for initiation of archaeal DNA replication. The results also have implications for the understanding of cell-cyele regulation in eukaryotes. n

Archaeal cell cycle regulation

An effective representation of the electronic structure of molecules must be properly based on quantum mechanics. Thus, we have developed the structure representation using quantum topology (StruQT) method where the electronic structure of molecuLes is re presented as critical points on the electron density distribution. StruQT is based on the Atoms in Molecules (MM) theory by Richard Bader. Comparing molecules in this representation means comparing sets of critical points and their properties for the diff erent molecules involved. However, the StruQT method needs automatic routines for finding comparable critical points between molecules. Two approaches are suggested: - The use of inductive logic programming (ILP) which is a non-attribute based method from machine learning. ILP has been used successfully in drug design and is much lesssensitive to the problem of finding comparable molecular features. - The use of scale space trees of the critical points on the electron densities. Sca le space analysis from the field of image analysis performs multiple smoothings of the electron densities to create a 4-D space where critical points merge into a hierarchy of simpler structures. These bifurcating critical point trees can be used to find comparable critical points between molecules.  The project has changed direction from creating its own software for finding critical points in scalar fields to using a commercial program and focusing on the modeling aspect of using AIM descriptors in QSAR/QSPR. In particular we are investigating the u se of inductive logic programming (ILP) which is very suitable for representing and comparing graph-like structure without having to perform 3D alignments. We will also investigate other non-alignment method approaches based on nearest neighbour geometrie s in combination with bond critical point (BCP) descriptors.A discretisation of the BCP for use with ILP will also be investigated.

An improved method for comparing the 3-D electronic structure of molecules in rational drug design

It has long been realized that close inbreeding can be detrimental to offspring fitness. Such inbreeding depression is caused by the increased homozygosity at loci that affect fitness. Recently, some exciting studies on birds and mammals have revealed a s imilar effect also in natural outbred populations, in which various fitness parameters are positively correlated with the degree of heterozygosity at a number of non-coding loci (microsatellite DNA). The marker loci are presumably linked with loci of key  importance for fitness. This discovery opens up a new and powerful tool to assess genetic effects. 
The project has two main objectives. First, we will investigate the effect of heterozygosity on individual reproductive performance and survival in a few  selected long-term studies of bird populations in Norway. We will seek to identify particular fitness components for which heterozygosity is important. Second, we will test predictions of the hypothesis that extra-pair mating systems are driven by hetero zygosity benefits. We will here specifically use bird species where a genetic benefit to female extra-pair copulations has been documented or is strongly indicated by existing evidence. The project will be carried out in collaboration with several other r esearch groups in Norway.

The role of heterozygosity for individual fitness and mating system evolution in birds

Climatic variation may affect evolutionary patterns by altering rates of speciation and extinction through changing availablity of appropriate habitats. In the proposed project, we assess the relationship between environmental change and evolutionary even ts using comparative phylogeography among 10 bovid species distributed across sub-Saharan Africa. Congruence in phylogeographic patterns among species as well as among areas will be tested using species from three differerent ecological groups (savannah-a dapted specialists, forest-adapted specialists and generalist species that can cope with a range o f different habitats). If large-scale changes in the physical environment act as a major determinant of evolutionary events, we expect phylogeographic congr uence across species from the same ecological groups as well as across geographic regions. In addition to the main objective of the study, we address whether specialist species are more prone to climatic change as compared to generalist species, and wheth er specific geographic regions serve as centres of origin for a large proportion of the stu died species. We anticipate that the project will provide valuable empirical data on the relationship between environmental change and evolutionary events and cont ribute to the understanding of the underlying mechanisms associated with evolutionarychange , ultimately leading to speciation and extinction.              change

Environmental change and evolutionary events - a molecular approach using comparative phylogeography among African bovids

It has been shown that synergistic interactions between mucins and alginates can result in enhaneed rkeological properties and gel formation. This behaviour has wide ranging implications both for pharmaceutical uses of alginates and as a complicating fact or in the lungs of cystic fibrosis patients infected with the alginate secreting bacterium Pseudomonas aeruginosa. However, the data available on the rheological behaviour of mixed mucin alginate systems is limited and no att empts have been made to understand the mechanisms underlying the observed gelation. This project will address the conditions that must be satisfied for mixed mucin alginate gels to form in relation to the mucin and alginate components as well as solvent c onditions such as ionic strength. It will be developed to study the interactions and mechanisms that result in mixed gel formation. This knowledge will then be applied to the study of sputum from cystic fibrosis patients with and without Pseudomonas ae ruginosa infection in an attempt to identify the contribution of mucin alginate gelation to the 'thick' mucus in the lungs of these patients. In vitro studies will be used to investigate mechanisms of disrupting such interactions.

Mucin alginate interactions

We are studying how olfactory and taste information is encoded in receptor and interneurones in the brain of insects and how learning of odours is realised via synapses of neurones connecting different brain compartments. As model organisms are used moths of the subfamily Heliothinae. The methods involve extra- and intracellular recordings combined with staining, for functional and morphological characterisations of the neurones. By the use of confocal microscopy the neurones are 3-dimensionally reconstruc ted in the brain. Precise determination of the dendrite arborizations and the axon projections in the different neuropil structures of the brain requires a standard atlas of the moth brain with thc compartments in a reference frame. The atlas is made by t he help of the computer program AMIRA which allows free turning of the reconstructed model, resulting in visualisation from different angles. Then all reconstructed neurones can bc placed in one normalised brain model. This helps to determine the neuronal  network underlying processing of sensor> information and learning. The insect brain is well suited, since its small size allows a complete reconstruction of the whole preparatio n in confocal microscope.                          eparatio

Standard atlas of the brain of a model insect

The project aims at using cod Uracil-DNA glycosylase (cUNG) as a model system in the study of DNA recognition and cold activity. The cod UNG possesses typical cold adaptation features such as increased catalytic efficiency and reduced temperatur stability compared to human UNG. The crystal structure of cod UNG has recently been determined and shows similarity to the structures of human, herpes simplex virus and E.coli UNG. Furthermore, in the order of 30 mutants has so far been constructed and characteriz  ed at various levels. Characterization of mutants of cUNG in combination with structure analysis indicates a highly fine tuned mechanism responsible for the increased catalytic efficiency. Analysis of mutants with substitutions in loop regions and altera tions of the surface charge indicate that an increased local flexibility and an optimisation of the electrostatic potential cause the increased activity of the enzyme. These observations wil l be further explored by the use of crystal structure analysis c ombined with theoretical calculations on cUNG-DNA/inhibitor complexes. Crystal structure analysis and calculations will be applied on both complexes with native enzyme and on a series of muta nts. The results from the study are expected to provide increas es insight into the molecular basis of protein-DNA interaction and cold activity.

Structural and energetic aspects of protein DNA-recognition

The goals of the project are to clarify the environmental distribution and importance of bacterial mutator strains and to identify the mechanisms underlying the hyper-recombinogenic phenotype. Knowledge of the distribution, dynamics and selection of mutat or phenotypes is crucial for assessing the barriers to horizontal transfer of transgenes (from genetically modified organisms or other genes such as those conferring antibiotic resistance or enhanced pathogenicity to bacteria. Our hypotheses are 1) that m utator bacteria increase recombination rates in natural populations of bacteria and 2) that mutator strains of bacteria provide a major entryway for foreign DNA into bacterial populations. Selected strains collections will be a ssayed for the prevalence o f mutator phenotypes. Complementation and random mutagenesis techniques will be applied to identify genes involved in establishing mutator phenotypes. The molecular basis of identified mutators will be characterized further wit h respect to their ability  to incorporate species-foreign DNA. Advancing the insight to the environmental dynamics of mutators will greatly benefit the understanding of how antibiotic resistance and virulence arise among environmental bacterial pathogens such as those causing prob lems in agricultural practices. Moreo ver, the gene products affecting the stability and uptake of foreign DNA in bacteria will be identified, of particular importancein medical microbiology.

Mutator phenotypes: distribution, population dynamics, and impact on bacterial adaptation and evolution

Lichens result from a mutualistic symbiosis between a fungus and an alga, and as such they provide unique features. Unique to the lichens are asexual reproductive strategies that involve fungus and alga simultaneously, and in numerous cases sexual reprodu ction is rare or absent. Information is scarce on genetic variability of asexual taxa, and it is completely unknown what processes are underlying the evolution of asexual taxa from asexual ancestors, a scenario which molecular phylogenies have been demons trated to occur. Lichens also produce a high number of unique secondary metabolites, 'lichen substances'. Secondary metabolite patterns may or may not display infraspecific variation. Although secondary metabolites have been used extensively in lichen sys tematics, it is unknown to what extent chemical variation reflects infraspecific phylogeny. Furthermore, there are numerous cases of lichen species occurring in discrete habitats with little or no morphological separation. Again, nothing is known about th e genetic background to this peculiar pattern.             This project is concerned with the study of of these problems, using DNA sequence data from highly variable markers. Sequence data will be collapsed into haplotype networks. Through described meth ods for statistical testing, species status can be inferredand an insight into the speciation processes can be provided.

Speciation and species recognition in lichens

The project presented has been selected by NASA/ESA to be carried out on the International Space Station in 2004. The project is divided in 3 parts and these consist of both the pre-, in- and post-flight studies. 
* In Part I using Arabidopsis thaliana as  a model plant a multi-generation (seed-to-seed) experiment will be performed in the EMCS on the ISS. Growth and development will be followed using physiological parameters and relevant analytical methods: illumin ation, life support, humidity control ,wa ter supply and seed production. The growth, development and seed production will take place in Plant Cultivation Containers (PCC) which our Project Group have developed in a separate contract with ESA. 
* In Part II gene expression profiling, quantificati on and localisation in A. thaliana exposed to variable g-forces will be obtained by use of cDNA microarray, real-time PCR and transformed plants. As part of the pre-flight activity the expression of se veral thousand genes in A.thaliana seedlings exposed  to simulated micro-gravity and Earth gravity has already been analyzed on a cDNA microarray by the Project Group. Space samples will reveal genes and networks controlling plant development that are affected by gravity. 
* The last scientific goal will be  obtained in Part III where we will examine the circumnutations of ecotypes and mutants of Arabidopsis hypocotyls using the EMCS video camera. Studies of circumnutations are relevant for understanding synchronized cellu lar growth in general, spiralisatio n of growth and morphology and finally, symmetry in movement and anatomy of plants.

Molecular and plant physiological analyses of the micro-gravity effects on multi-generation studies of Arabidopsis thaliana

Grazing is an important factor for plant dynamics, but it has proved difficult to generalise about grazing impact, partly because of a lack of a good mechanistic framework linking the grazing impacts on certain life stages to the dynamics of the populatio ns. A functional classification of species has been central in order to understand and predict vegetation response-to the effect of grazing, but few studies have explored the importance of plant functional traits for plant dynamics in alpine/arctic habita ts. We will study relationships between sheep grazing and plant life history on three different levels. 1)	Plant community dynamics and sheep grazing: Can changes in plant community structure be related to specific life history traits within the resistanc e-tolerance mechanistic scheme? 2)	Dynamics of herbivore selected herb species in different grazing regimes: Do sets of plant traits covary to an extent that general strategies can be identified that explain plant response (tolerance or lack of tolerance)  to grazing? 3)	Grazing and plant population dynamics: How do species with contrasting life histories (10w stature versus tall competitive) respond in their population structure and expression of plant tolerance traits at different grazing levels?

The effect of sheep grazing on alpine plant communities, species and populations: what is the importance of plant life histories?

It is currently agreed that new neurons are added to continually growing structures and replace old and dying brain cells in adults of all major vertebrate taxa, a process known as neurogenesis. These structural processes may be highly important for behav iour, mood, and cognition in both animals and human beings. Stress can suppress neurogenesis, an effect that has been linked to the-development of stress-related psychiatric disorders. In animal models enhanced neurogenesis is seen in the brain after trea tment with antidepressant drugs that inhibit reuptake of the neurotransmitter serotonin (5-hydroxytryptamine), and thereby increase serotonergic signaling. Compared to mammals, neurogenesis persists into adulthood to a much higher degree in the central ne rvous system of teleost fish.                            We have recently shown that one week of dietary treatment with the serotonin precursor, the amino acid L-tryptophan, leads to decreased aggression and enhanced stress tolerance in rainbow trout. Sim ilar to antidepressant treatment in mammalian models, shorter term tryptophan treatment does not produce behavioural effects, suggesting that the serotonin precursor may act through structural modifications in the brain. This project aims to examine how s tressful experiences impact neurogenesis in the brain of rainbow trout, and whether these changes can be counteracted by enhanced serotonergicneurotransmission through dietary tryptophan treatment.

Stress and neurogenesis in rainbow trout

The genus Vibrio are among the most numerous and ubiquitous marine bacteria and commonly found as etiologic agents of diseases in both vertebrates and invertebrates throughout the world. Vibrio salmonicida, a marine gram-negative psychrophilic pathogen, t he etiological agent of Cold-water vibriosis (also called Hemorrhagic syndrome or Hitra disease) in Atlantic salmon and Atlantic cod, has been studied for some years. Although an efficient vaccine has been developed, the molecular mechanisms of host invas ion and specificity, colonization and growth are largely unknown.          In order to gain insight into these mechanisms, part of V. salmonicida genome will be sequenced, genes identified and analyzed. Finally, the V. salmonicida genome will also provide  a unique source of enzymes for the study of mechanisms for cold activity at a molecular levels and a valuable source of unique biomolecules in a bioprospectingperspective.

Whole-genome sequencing of Vibrio salmonicida

An important homeostatic liver function is to remove and degrade foreign molecules and cells from blood. This function is mediated by endocytosis-receptors expressed on parenchymal and nonparenchymal liver cells. Three important groups of such receptors a re Fc<.gamma.>-receptors (Fc<.gamma.>R), scavenger receptors (SR) and mannose receptors (MR). We have identified a MR, two types of Fc<.gamma.>Rs and two types of SR in rat liver cells (Kupifer cells (KC) and liver endothelial cells (LEC)). The ligands of these receptors are immune complexes, various denatured macromolecules (e.g. oxidized low density lipoproteins) and glycoproteins with terminal mannose, for respectively Fc<.gamma.>R, SR and MR. In the present project we wish (1) to clarify the intracellu lar transport of immune complexes in KC and LEC and to compare this itinerary with that followed by ligands of MR and SR, (2) to obtain information about the mechanisms of downregulation of the F c<.gamma.>R, (3) to identify possible signal molecules and transcription factors which regulate the expression of Fc<.gamma.>R and SR, and (4) to determine the role of the various endocytosis receptors (Fc<.gamma.>R and SR) in phagocytosis in KC. 
Methods: The studies will be performed with isolated liver cells and cell lines (COS cells, MIDCK cells, J774 cells). The cell lines offer the possibilities of transfecting genes for the receptors to be studies. Intracellular transport of ligands and receptors will be followed by means of confocal and electron microsc opy, and by subcellular fractionation. Phagocytosis will be studied using latex beads coated with IgG or SR and MR ligands. To study intracellular transport from endosomes to lysosomes (whichprobably takes place by fusion between late endosomes and lysoso mes) a cell free system will be employed. To study regulation of receptor expression the promoters of the receptor genes will be subcloned upstream of a reporter gen (luciferase) in J774 cel ls.

Turnover of immune complexes in liver

Prosjektet går ut på å forstå de genetiske mekanismene som ligger til grunn for endosperm-utvikling. En har nylig identifisert og karakterisert Dek1-genet fra mais, det første medlem av calpain gen-superfamilien beskrevet hos planter, og som er en av hove dregulatorene i signal-transduksjonssystemet for aleuron celler i endospermen. I tillegg tyder flere resultater på at Dek1 er involvert i signal-transduksjonskjeder som også har global viktighet for planteutvikling. Det morfogenetiske programmet for endos perm-utvikling er tilsvarende for alle arter med nukleær endosperm, bl.a. alle kornartene og Arabidopsis. Hovedstrategien i prosjektet blir derfor å utnytte resultatene fra arbeider i mais, og bygge videre på disse ved å benytte modellorganismen Arabidops is, hvor det forventes at resultater vil oppnås raskere enn i kornartene. Mais vil også brukes som system der dette er naturlig. Prosjektet blir konsentrert om tre områder: 
<h>1. Undersøke mekanismene for regulering og funksjon av DEK1 proteinet 
<h>2. I dentifisere og karakterisere andre faktorer som virker direkte sammen med DEK1 i signaltransduksjons-kjeden 
<h>3. Undersøke samspillet mellom Dek1 og andre gener som er involvert i aleuron celleutvikling som ikke har direkte interaksjoner med DEK1 protei net.

Elucidation of the role of DEK1 in endosperm development and plant signal transduction

Coevolutionary dynamics allow revealing ongoing mecroevolutionary dynamics and adaptations. Interactions between obligate avian brood parasites and their hosts are suitable systems for the study of coevolution. Various adaptations and counter-adaptations  have previously been described in both parasites and hosts. Spatial differentiation of various populations of hosts and parasites into metapopulations may lead to local adaptations in the interacting species. In this project, the evolution of host and pa rasite adaptations will be studied in specific host populations in time and space, by analysing egg clutches in museum collecitons and in the field. By identifying and comparing various host and parasite popula tions, we will examine if local adaptations  in host and parasite eggphenotypes exist in a European brood parasite and a common host. In addition, by applying the concepts of metapopulation dynamics, the expected behaviour of hosts towards parasites in spe cific populations will be modelled. Few st udies have focused on local adaptations in various subpopulations in a metapopulation scenario. Our approach is thus not only likely to be important in a coevolutionary context, but also aimed at improving our und erstanding of evolutionary biology in gen eral, biodiversity and conservation biology. Modern techniques including photospectrometry and molecular analyses will be applied in this project.

Local adaptations in cuckoos and their hosts; a metapopulation approach

Time series analysis has found that small rodent population cycles may be driven by an interaction between food shortage during winters and delayed density dependence caused by predators. The region where small rodents exhibit cyclic dynamics have long la sting thick snow cover that probably facilitates the cycles. The layer between the snow and the ground will under some circumstances be transferred to a layer of fragile pyramidal ice crystals making the subnivean space. Small rodents sustain life through out the winter in the subnivean space. The subnivean space is fragmented by ice frozen to the ground that effectively reduce carrying capacity and may promote overgrazing. Overgrazing might be most prevalent during snowme lt when the small rodents are for ced by water from the melting snow to higher ground. The aim of this study is to experimentally test how much small rodent survival is dependent on access to food patches under the snow and to develop and parameterize an explicit functional response model  to test whether the small rodent population cycle ca n be driven by a plant-herbivore interaction. Access to food will be manipulated by creating a network of artificialtunnels under the snow permitting access to else un-accessible food patches.

Does access to food patches limit microtine winter survival during the cyclic population decline? An experimental study

Seeds and seedlings are vulnerable stages in the life cycles of plants, and we expect strong fitness consequences of environmental variability on these stages. Climate has a major influence on vegetation, and in species with wide geographical or altitudin al distributions, the factors and processes controlling seedling mortality risk are unlikely to be constant throughout the range. In Part 1 I quantify variation in seed dormancy levels along climatic gradients in Norway. Two hypotheses about climate effec ts on germination are tested, namely that dormancy levels should increase (1) with the severity or (2) with the unpredictability of winter climate. While phytotron screening has the advantage of being efficient and enabli ng precise quantification and eva luation of between-population differences, it has the disadvantage of providing relatively unrealistic estimates of field behaviour. In Part 2 a reciprocal seed burial experiment is performed along an altitudinal gradient. Here I test the effect of differ ences in (i) dormancy levels and (2) environmental conditions for seed survival for actual seed carry-over across years. Parts 1 and 2 are both replicated as several species are studied simultaneously. This enables the evaluation of differences in the rel ative magnitude of the responses in light of species biology.

The effect of climate on seed renegation strategies: Population-scale experimental tests on four Veronica species

Candida albicans is an opportunistic pathogen that causes life-threatening, systemic disease in immuno-compromised individuals, such as patients undergoing chemotherapy. Patients with catheters and joint replacements are predisposed to systemic fungal dis ease because C. albicans forms sessile communities of microorganisms, known as biofilms, on inorganic surfaces. These biofilms are resistant to antifungal agents and cause recurrent infections that are difficult to treat. I intend to identify genes that a re necessary for C. albicans biofilm formation. First, I will test whether any of the known adhesins and morphogenetic regulators in C. albicans are necessary for biofilm growth. Second, I will use S. cerevisiae to screen for C. albicans genes involved in  adherence to PVC. This experiment should identify genes involved in the initial step of biofilm formation, surface attachment. Finally I will use an antisense RNA inhibition strategy to screen for genes necessary for biof ilm growth in the presence and a bsence of antifungals. These approaches should allow me to identify genes necessary for both initial and later stages of biofilm formation and may provide insights into the origin of the antifungal resistance of biofilm grown cells.

Biofilm formation in Candida albicans

Signalformidling mellom nerveceller skjer ved at kjemiske signalstoffer frigjort fra en nervecelle reagerer med spesifikke reseptorer på den andre og stimulerer eller hemmer dens aktivitet. Glutamat and GABA er henholdsvis viktigste stimulerende og hemmen de signalstoff i hjernen. De er oppkonsentrert og lagret i såkalte synaptiske vesikler i nerveterminaler. Det antas at glutamat og GABA dannes fra glutamin som syntetiseres i gliaceller og som dernest transporteres til nerveterminaler. Jenstad har konsent rert seg om en glutamintransportør, SA1/SAT2, som uttrykkes i mange organer. I sentralnervesystemet uttrykkes SAT2 i nerveceller. En ønsker å undersøke om SAT2 bidrar til transporten av glutamin inn i nerveceller for produksjon av transmittere. Jenstad ha r laget et GST-fusjonsprotein inneholdende deler av dette proteinet og immunisert kaniner for produksjon av antistoff. Serum fra tre forskjellige kaniner er blitt affinitetsrenset, og gir på Western blot spesifikt bånd i samsvar med Monica Jenstad har ilø pet av rapportperioden også deltatt i flere andre prosjekter: 
To typer membranlipider, galactosylsphingosine (GalSph) og glucosylsphingosine (GlcSph), akkumuleres i kroppen ved sykdommene Krabbe's og Gaucher's disease. Det fører til demyelinisering av ak soner og resulterer i neurologiske defekter og til tidlig død hos affiserte pasienter. Det er vist at disse lipidene er toksiske for humane natural killer cells (NK-celler). En har nå vist at NK-celler uttrykker spesifikke reseptorer for disse lipidene. V idere har en vist at slike glycosphingolipider induserer apoptose i NK celler in vitro, og i dyremodeller. 
Monica Jenstad har uttrykt glutamintransportøren SAT1 (en homolog av SAT2) i PC12-celler (utgått fra binyremargceller). Cellene er så inkubert i et  medium som inneholder NGF (nerve growth factor), og differensierer til modne nerveceller med sine prosesser. Jenstad har gjort dobbeltmerkingsforsøk med forskjellige markører for å undersøke om SAT1 spesifikt blir transport mot aksonterminalen. I motsetn ing til SAT2 uttrykkes SAT1 fortrinnsvis i interneuroner, og vil derfor spesielt være viktig for inhibitorisk transmisjon. Disse resultatene vil inngå i et større arbeide over karakteriseringen av denne transportøren og dens funksjon i sentralnervesysteme t.

Molecular analysis of a neuronal glutamine transporter, SA2, involved in transmitter recycling

1. An experimental study will be conducted for testing some general mechanisms hypothesized to promote of co-existence of competing species in patchy habitats. As our model system we will use two small rodent species (the field vole and the root vole) wit h well-known population biology. However, the geographic distribution pattern of the two species in Europe is peculiar and poorly understood and one of our goals will be to investigate the role of inter-specific competition in combination with predation a nd habitat quality as possible determinants of their large-scale distribution patterns. The experiment will have a multi-factorial design as to evaluate the different mechanisms simultaneously and thereby be able to test for biologically interactive effec ts between the mechanisms. This experiment will significantly advance the study of inter -specific competition in general and train the postdoc candidate in advanced experimental designs and analysis. 2. A multi-annual data set from an observational study  of the spatiotemporal dynamics of the two species in a natural habitat mosaic will be analyzed. This study will be complimentary to the experiment in the sense that the interaction between the field v ole and the root vole will be explored at the larger  spatial and a longer temporal scale. 3. Through collaboration with Dr. David Lindenmayer's group at the Center for Resource and Environmental studies in Canberra, Australia, learn methods of spetially explicit modeling of community and population dynamic sby applying such methods on the data set from the observational study.        by applying such methods on the data

Mechanisms of species co-existence in patchy habitats

A recent approach in ecology, ecological stoichiometry, recognises resource quality (nutrient ratios) as a limiting factor in addition to resource quantity. In the proposed project, we will apply this approach to study classical population-ecological prob lems in a new perspective. Theoretical models of consumer resource systems have predicted dramatic and counter-intuitive changes in population dynamics, when nutrient recycling and nutrient-limited growth are considered. However, most of these models are  not yet evaluated experimentally. An important prediction is that increased phosphorous enrichment leads to more unstable population dynamics of the consumer, and eventually to extinction, although the resource persists. We will test this prediction by e xposing laboratory systems of zoopl ankton (Daphnia) and algae to a range of phosphorous concentrations, and study the long-term dynamics of the system. Using ion-parametric modelling, we aim at developing a new statistical]y-derived model for this system . Such models make Few a priori assu mptions about the form of the functions, and are therefore well-suited for exploring unknown relationships among variables. By combining such a flexible modelling approach with the stoichiometric perspective, we expect  to provide new insight into general ecological problems.

Population dynamics and stoichiometry of consumer-resource systems: a combined experimental and modelling approach

Parasitism is a constant threat to human health, food production and wildlife conservation. Some species, or strains, produce highly lethal diseases while others are benign. Trying to understand the reasons for this variation in virulence is one of the ma jor challenges in epidemiology. In this project we will test one of the fundamental assumptions on which virulence theory is based on, but where the empirical evidence is poo r: is there a trade off between virulence and transmission that will stop virule nce from escalating? We will use a simple experimental model, consisting of the planktonic crustacean Daphnia magna and the bacterium Pasteuria ramosa. In this system bacteria l spores are released only after the host is dead, which makes it ideal for mea surements of parasite fitness. We will select for high and low virulence, and test ifthe most virulent strains reach an optimal level in terms of fitness.

Testing the cost-of-virulence hypothesis: Does a horizontally transmitted parasite have an optimal virulence?

The main aspiration of the field of Artificial Life is to implement life-like entities in agent-based computer models (ABM). Although relatively successfull in the past, the available models today still do not reflect the rich hierarchical organisation of real organisms (molecules, cell, organs...). It has been proven to be difficult to make ABMs which support the spontaneous emergence of more than one level. It is a challenge for the field of Artificial Life to learn how to do this. One part of the proje  ct is therefore to examine how ABMs have to be made in order to support hierarchical organisation. 
The second part of the project will examine the way Artificial Life produces knowledge. ABM are a reductionistic way of doing research on life and there a re strong (if abstract) arguments against their adequacy or for the proper understanding of organisms(especially advocated by Robert Rosen). It is however unclear what the relevance of these arguments for the practical work in Artificial Life is and what  possible alternatives to a reductionist Artificiai Life are.

The emergence of hierarchcal organisation in artificial life systems - Theoretical and meta-theoretical problems

Most birds are classified as socially monogamous, yet they frequently engage in extrapair copulations. In the bluethroat, females copulate frequently with neighbouring males with the result that around 30% of offspring are sired extrapair. The bluethroat  is one of the few bird species in the world in which a genetic benefit to female extra-pair copulation has been identified, viz. an enhanced cellular immunocompetence of extrapair young. The benefit seems to arise as females seek fertilizations with male sthat have a genotype compatible to their own, rather than with males that have a high quality genotype per se. How females choose compatible males is not known. The current project aims at explaining how females choose extrapair sires and the extent to w hich female choice is influenced by male advertisement behaviour. The similarity in genotypes between females and their social and extrapair mates will be examine d for MHC genes that play an important role in the immune defense against pathogens. Experim ents will be performed to reveal whether there is a behavioral or a postcopulatory mechanism, which allows females to select genetically compatible extrapair sires . The project will also manipulate male advertisement behaviour to assess its influence on  male fertilization success.

Behavioural and genetic mechanisms of extrapair fertilization in bluethroats

Sexually selected signals can be viewed as life history traits. In the guppy (Poecilia reticulata) and the sex role reversed pipefishe (Syngnathus typhle) sexual signals are well understood, but their relation to life history decisions remain unexplored.T he proposed project will test how life history traits, resource budgets and predation risks affect female ornament display and female-female competition in these two species. How are these trade-offs affected by a female's resource budget? Does predationr isk affect trade-offs? Under environmental, will allocation to body size, to ornament display, to competition or to eggs suffer first? Furthermore, do the two characters primarily used to attract males, body size and ornamentation, differ in costs to the  females. Do females with different resource budgets differ in their allocation to growth and ornamentation? Mutual mate choice and mati ng competition is another poorly investigated area. Does the most choosy sex compete over the best partner, and are th e best competitive individuals choosy? Can poor individuals of the choosy sex afford to be choosy, or do they need to court? How mutual m ate choice and mating competition interact with life history is a fascinating but so far poorly understood field of r esearch.

Sexual signals and life history trade-offs in guppy and sex-role reversed pipefishes

Organismer er utsatt for ulike typer stress, som ofte virker sammen. Enkelte av organismenes forsvarsmekanismer mot stress er basert på bruk av samme kjemiske ressurs, slik at det kan oppstå en konkurransesituasjon mellom mekanismene. Et eksempel på en sl ik konkurransesituasjon har man i organismenes forsvar mot toksisk metall og mot fryseskader ved lav temperatur, idet begge er basert på proteiner med et ekstremt høyt innhold av aminosyren cystein. Både metallbindende protein og antifryseproteiner hos in vertebrater er vist ha innpå 30 % cystein. Har denne konkurransesituasjonen ført til at de mest metalleksponerte organismer baserer sin kuldeherdning på frysetoleranse, som krever isnukleerende lipoproteiner uten mye cystein? En vil undersøke om metalleks ponering reduserer fryseunnvikende insekters evne til å produsere antifryseprotein. Om fryseunnvikende arter gjennomgående har lavere metallinnhold enn frysetolerante arter, om arter som kan skifte fra den ene kuldeherdningsform til den andre gjør dette s om en følge av metalleksponering og om isnukleatorene hos de frysetolerante artene også hjelper til med å binde metaller, som øker sterkt i konsentrasjon når organismene fryser.

PES-POS-Prosjektetablererstøtte EU

Posisjonering i forbindelse med 7. rammeprogram

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