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Prosjekttilbud - Forskerlinjen - Medisinstudiet

Her legges det ut prosjekttilbud som er særskilt meldt inn av veiledere. Få ideer til forskningsprosjekter og tematiske forskningsområder ved å se på instituttenes web-sider, oversikt over instituttgrupper og forskergrupper. Ta gjerne direkte kontakt med gruppenes kontaktpersoner for mer informasjon.

Project - Causative mechanism through which obesity increases cancer risk

With over 4 billion adults and nearly 3 million children being overweight or obese, this is a significant global health concern. The bulk of epidemiological studies has revealed: i) organ-dependent association between obesity and cancer risk (colon and rectum, pancreas, upper stomach, gallbladder, liver, esophagus, breast, thyroid, kidney, ovary, uterus, brain, blood, lymph tissue, head and neck, and bladder); and ii) time-dependent association, i.e., the longer exposures to overweight the higher risk of cancer; and the earlier overweight in childhood the higher cancer risk at late adulthood. Much is known about the impact of obesity and physical activity on the cancers, but many questions remain unanswered. For instance, why does obesity increase the cancer risk in some organs but not others? How do bariatric surgeries influence cancer risk? Does weight loss impact or can it reverse cancer risk, if so, what is the biological mechanism(s) involved? why is there no “dose”-dependent relationship, i.e., the degree of overweight and obesity vs cancer risk?

In collaboration with Department of Surgery at Namsos Hospital, we are particularly interested in studying pancreatic cancer and gastric cancer in connection with overweight or obesity in order to develop new interventions of prevention and treatment.

If you dare to think differently and are willing to take up challenges in your professional career plan, please contact us for discussion on research ideas and individual research plan in line with your interest and feasibility during the next three years (two summers and two semesters).

Duan Chen, Professor of Experimental Surgery at Department of Clinical and Molecular Medicine, NTNU at duan.chen@ntnu.no as main supervisor.

Gøran Troseth Andersen, Surgical Consultant at Department of Gastrointestinal Surgery, Namsos Hospital at GoranTroseth.Andersen@helse-nordtrondelag.no as co-supervisor.

GluCEST as a translational biomarker of synaptic dysfunction in Alzheimer's disease

Main supervisor: Asgeir Kobro-Flatmoen (asgeir.kobro-flatmoen@ntnu.no), researcher, Kavli Institute for Systems Neuroscience

Co-supervisors: Axel Karl Gottfrid Nyman (axel.nyman@ntnu.no), postdoctor INB, neurology resident St Olavs Hospital; Pål Erik Goa (pal.e.goa@ntnu.no), professor, Department of Physics

Funded by: NTNU Biotechonology

Background

The human brain contains almost a hundred billion neurons. The higher cognitive functions necessary for social participation and a rich and meaningful life arise as a result of the communication of these neurons across almost a thousand trillion synapses. The majority of synapses in the cortex (80-90 %) are glutamatergic. Altered glutamatergic transmission is implicated in major headache disorders, epilepsy and psychiatric disorders. All neurodegenerative disorders are accompanied by dysfunction and loss of synapses, and most dementias start with subtle cognitive dysfunction without evidence of tissue loss. Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is no exception: The accumulation of pathological proteins in the brain is strongly associated with memory loss and loss of glutamate years before structural brain imaging can detect signs of disease. A method of non-invasively measuring glutamatergic synapse function would therefore be key for (1) establishing “missing links” between pathology and function, (2) diagnosing disease in an early phase, and (3) finding targets for and measuring effects of early clinical interventions. While no such technique is implemented today, one candidate is glutamate-weighted chemical exchange saturated transfer MRI (gluCEST).

Aims of the project

In this pilot project, we wish to implement gluCEST on the advanced rodent and human brain imaging infrastructure available at NTNU, validate it for a rodent model of Alzheimer’s disease and exemplify it in patients with sporadic Alzheimer’s disease. The validation in rodents will be performed using immunohistochemistry and state- of the art mass spectrometry imaging of brain slices (MALDI-MSI) available at NTNU. The successful implementation of gluCEST at NTNU would open up the way for a large number of clinical and preclinical studies of fundamental aspects of brain disorders.

Possible tasks for a Forskerlinjestudent

As a Forskerlinjestudent, you will learn and work with one or several of the above-mentioned techniques, depending on your interest. You will be part of a research environment with a strong translational focus, in collaboration with the K. G. Jebsen Center for Alzheimer’s Disease, the Kavli Institute for Systems Neuroscience, the Neuroclinic at St Olavs Hospital, the MR groups at the Department of Circulation and Imaging and the Department of Physics. You will be given the opportunity to work with all aspects of translational research, from patient recruitment and inclusion to advanced laboratory techniques.

Kroniske underlivssmerter blant kvinner i HUNT

Hovedveileder: Førsteamanuensis Cecilie T. Hagemann, Institutt for klinisk og molekylær medisin, NTNU og Kvinneklinikken, St. Olavs hospital

Biveiledere: Professor Tom Ivar Lund Nilsen, Institutt for samfunnsmedisin og sykepleie, NTNU; kvinnehelsefysioterapeut og forsker Signe Nilsen Stafne, Rehabiliteringsklinikken, St. Olavs hospital; førsteamanuensis og psykolog Tormod Landmark, smertepoliklinikken, St. Olavs hospital og Institutt for sirkulasjon og bildediagnostikk, NTNU.

Bakgrunn

Forekomsten av kroniske underlivssmerter (chronic pelvic pain, CPP) blant kvinner har i ulike studier variert mellom 6 og 25 %. I en dansk studie med 1200 tilfeldig utvalgte kvinner fra befolkningen fant man at 11% oppga å ha CPP. Vi vet imidlertid mindre om forekomsten blant norske kvinner. Kroniske underlivssmerter kan ha betydelig påvirkning på arbeidsevne, sosialt liv, parrelasjon og seksualliv, samt redusere livskvalitet og psykisk helse.

Definisjonen av kroniske underlivssmerter varierer imidlertid i ulike studier. De fleste inkluderer en varighet av plager på > 6 mnd. og en lokalisasjon av smerten i nedre del av magen. The International Association of the Study of Pain (IASP) derimot legger vekt på at smerten skal oppleves å komme fra strukturer i bekkenet, og være assosiert med negative konsekvenser for personen.

Formål

Formålet med denne studien er å undersøke forekomsten av kroniske underlivssmerter blant kvinner i HUNT, samt å få de som har smerter til å beskrive nærmere detaljer om hvordan smertene oppleves og hvordan dette påvirker deres daglige aktiviteter.

Vi vil også vurdere om ett enkelt spørsmål om kroniske underlivssmerter brukt under feltstasjonen i HUNT4 kan identifisere de kvinnene som faktisk har slike smerter. Dette er avgjørende for om man kan stole på den CPP-prevalensen blant norske kvinner som fremkommer ut fra tallene i HUNT4.

Resultatet vil ha betydning for videre planlagte studier som ser på sammenheng mellom CPP og ulike risikofaktorer.

Materiale og metode

Dette vil være en tverrsnittsstudie som tar utgangspunkt i besvarelsene til kvinner som i perioden 2017-2019 har deltatt på feltstasjonen i HUNT4. Det er 29245 kvinner i HUNT4 som har besvart spørsmålet: "Har du, eller har du hatt, underlivssmerter som har vart i minst 6 måneder?" I alt 2140 kvinner (7%) har svart ja.

Vi planlegger nå å sende ut noen tilleggsspørsmål til alle de 29245 kvinnene som deltok i HUNT4. Spørreskjemaet skal sendes ut elektronisk og inkluderer også et elektronisk kroppskart (GRIP) der deltakeren også kan markere om hun har smerter i andre kroppsdeler enn underliv. Her vil vi kartlegge varighet, hyppighet og intensitet av smertene, hvor plagsomme de oppleves og smertenes påvirkning på daglige aktiviteter, søvn, sexliv og parrelasjon.

REK- Midt har godkjent prosjektet i februar 2022. Spørreskjemaet (og informasjonsskriv) er tilnærmet ferdigstilt og godkjent av administrasjonen i HUNT databank (HUNT Data Access Committee (DAC)), og undersøkelsen har fått en egen nettside under HUNT: https://www.ntnu.no/hunt/underlivssmerter . Spørreskjemaet er bygget i Nettskjema ved Universitetet i Oslo og vi har opprettet et Tjenester for Sensitive Data (TSD)-prosjekt. Sammen med HUNT administrasjonen vil TSD stå for en sikker digital løsning med elektronisk utsendelse av SMS med lenke til digitalt informasjonsskriv, til samtykkeskjema og til spørreskjemaet.

Nytteverdi

Det er lite kunnskap om forekomst av kroniske underlivssmerter blant norske kvinner. Gjennom dette prosjektet bruker vi et kroppskart med tilleggsspørsmål som kan hjelpe kvinner til å bli mer bevisst på egne plager og smerter, og med det oppsøke mulig helsehjelp for plagene. Kroppskartet med tilleggsspørsmålene kan også vise seg å være nyttig kartleggingsverktøy før f.eks. kliniske undersøkelser. Indirekte vil studien kunne bidra til at samfunnet og helsevesenet fokuserer mer på slik kartlegging og i neste omgang mulig helsehjelp/behandling av lidelsen.

Generelt om prosjektet

Denne studien er en understudie av et større ph.d. prosjekt kalt: «Are adverse childhood experiences and mental distress risk factors for chronic pelvic pain? A prospective population-based study».

Denne delstudien egner seg fint til et forskerlinjeprosjekt der man tar sikte på å skrive to vitenskapelige artikler. Forskerlinjestudenten vil imidlertid være en naturlig deltaker i forskningsgruppa på det større HUNT underlivssmerte-prosjektet, og kan med det få tilgang til datamateriale for en tredjeartikkel for å fullføre en ph.d. med korttidsstipend etter endt embetseksamen.

Forskerlinjestudenten vil få veiledere som brenner for dette prosjektet, som har god erfaring i å veilede alt fra hovedoppgavestudenter til ph.d. kandidater. Studenten vil få tett oppfølging slik at dette prosjektet skal bli en suksess.

Studier på vekst av hjernesvulster

Hovedveileder:Prof. Sverre H. Torp (sverre.torp@ntnu.no), Institutt for klinisk og molekylær medisin, NTNU; Avd. for patologi, St. Olavs hospital.

Biveileder:Førsteamanuensis Anne Jarstein Skjulsvik (anne.j.skjulsvik@ntnu.no), Institutt for klinisk og molekylær medisin, NTNU; Avd. for patologi, St. Olavs hospital og Prof. Ole Solheim (ole.solheim@ntnu.no), Inst. for nevromedisin og bevegelsesvitenskap, NTNU; Nevrokirurgisk avdeling, St. Olavs hospital.

Bakgrunn

Hjernesvulster er en meget heterogen gruppe, og det rammer ca. 1000 voksne i Norge årlig. Vanligste behandlingsformer er kirurgi og stråling, men også cellegift kan ha effekt. Til tross for fremskritt innen nevrokirurgi, bildediagnostikk og andre behandlingsformer, så er fortsatt prognosen dårlig for mange pasienter med hjernesvulst. Andre problemer er de kliniske effektene tumor har på hjernen og de komplikasjoner som kan oppstå etter behandling. I den anledning er det viktig å få stilt riktig diagnose tidlig og få selektert de pasienter med en aggressiv hjernetumor, slik at disse pasientene kan få best mulig behandling og oppfølging.

Den hyppigste og mest maligne hjernesvulsten hos mennesker, er glioblastom, ca. 200 får denne diagnosen årlig i Norge. Insidensen øker med alder, og median alder for sykdomsdebut er rundt 60 år. Ubehandlet dør ca. 90 % av disse pasientene etter diagnosetidspunkt. Ved optimal behandling med kirurgi, stråling og cellegift er median overlevelse på vel halvannet år. Det er således viktig å studere denne svulstens biologi som grunnlag for utvikling av nye behandlingsformer.

Nylig er det utført studier her ved St. Olav hospital på glioblastomer og deres vekstrate. Ved å sammenligne to serier av MR-bilder (diagnostisk og preoperativt) så har man klart å estimere vekstkurver for disse svulstene og på basis av dette kunne inndele dem i to grupper: saktevoksende og hurtigvoksende.

På dette materialet har det vært gjort en rekke undersøkelser når det gjelder kliniske parametre, bildediagnostikk og histopatologi, hvilket har gitt grunnlag for flere publikasjoner og phd’er. Vi har bl.a. studert histopatologiske aspekt, karpatologi, mikroglia/makrofagreaksjon, m.m.

Det aktuelle nå er å fortsette studier på dette tumormaterialet med videre fokus på mikroglia/makrofagers rolle for tumorvekst i glioblastomer, men også vurdere betydningen av proliferativ aktivitet og molekylærgenetiske forandringer.

Pasientmateriale og metoder

I dette prosjektet inngår ca. 90 pasienter opererte for glioblastom. Vi har solide kliniske data inkludert vekstrater, samt mange histopatologiske forandringer registrert. Selve prosjektet inneholder tre delprosjekter:

  1. Mikroglia/makrofagers effekter på tumorvekst.
    Her har vi allerede en del data basert på immunhistokjemi, slik at man raskt kan komme i gang med første publikasjonen.
  2. Korrelasjon mellom tumorvekst og proliferasjonsmarkører.
    Her er hensikten å vurdere proliferativ aktivitet vurdert immunhistokjemisk med antistoffer mot ulike proliferasjonsassosierte proteiner (som Ki-67, fosfohiston H3 og Aurora-A) og tumorvekst.
  3. Molekylære subgrupper av glioblastomer og tumorvekst.
    Glioblastom består molekylærgenetisk av tre subtyper (proneural, mesenkymal og klassisk type), og i denne studien ønsker vi å se på relasjonen mellom disse subtypene og tumorvekst.

De metoder som vil inngå i prosjektet, er tradisjonell histopatologi/lysmikroskopi, immunhistokjemi og molekylærgenetiske analyser. Disse analysene vil bli utført av teknisk personale på NTNU og Avd. for patologi, St. Olavs hospital.

Generelt om prosjektet

Dette prosjektet er et godt eksempel på translasjonsforskning med innslag av både basal og klinisk forskning. Selve prosjektet er altså typisk kreftforskning som omfatter helt sentrale tema når det gjelder glioblastomer. Prosjektet er vel designet for tre publikasjoner som gjør at det er realiserbart innenfor de gjeldende tidsrammene (tiden som forskerlinjestudent og korttidsstipend etter endt embetseksamen). Et vesentlig styrke ved prosjektet er også at veilederne har god erfaring i å veilede forskerlinjestudenter og phd-kandidater, og de kjenner metodikken og pasientmaterialet godt. Opplæringen er grundig, og du som kandidat vil få tett oppfølging. En annen stor fordel er også at vi hele tiden er lett tilgjengelige for råd og spørsmål.

Treatment resistant in late-life depression: clinical and neuroimaging approaches

Number of students wanted: 1-2

Main supervisor (your name and contact information):

Associate Professor Maryam Ziaei (maryam.ziaei@ntnu.no)

Dr Pål Sandvik (pal.sandvik@stolav.no)

Associate Professor John Christian Fløvig (John.Christian.Flovig@stolav.no)

Background and Objectives:

With the global population rapidly aging and depression being the leading cause of disability worldwide, identification of factors that prevent late-life depression (LLD) is of paramount public health importance. The LLD affects more than 10% of the growing geriatric population, with more of both psychiatric and somatic disorders urges for additional health and social services, while resources are limited. Clinicians are already seeing increased referrals for older patients with more comorbidity requiring a higher level of multidisciplinary clinical expertise and combined treatments. Thus, being able to provide expected treatments to a population of older people constitutes a major health challenge, which emphasizes the importance of developing preventive measures. Mental disorders impact brain’s structure and function, increasing the risk of social, psychological, and somatic conditions, requiring more research to find key points for intervention. Given the heterogeneity of mental health disorders and LLD specifically, it is critical to develop viable biomarkers to tailor therapeutic interventions. In this interdisciplinary research, we aim to examine how different factors contribute to the understanding of resilience and relapse of patients with LLD, combining unique ultra-high-resolution brain imaging with novel, wearable technologies, and interpretable machine learning methods. With this unique combination of expertise and methods, we shall identify whether patients are responsive to medications and whether we can predict patients who will likely relapse. Our findings will open new avenues for personalized medication and contribute to the ever-growing field of precise psychiatry.

In this project, with strong collaboration between geriatric psychiatry and Kavli institute, we investigate behavioral and neurocognitive mechanisms underlying protective factors in late life depression, with the question that why some individuals show relapses of episodes while others respond to medications better.

Methods:

We use a variety of methods such as behavioral and neuroimaging techniques to investigate behavioral, structural, and functional changes related to emotional processes in healthy aged population and among late-life depressed individuals. We use functional magnetic resonance imaging (fMRI) to measure brain activity associated with a cognitive task implemented in the scanner.

Student requirements:

Students are given a chance of getting involved in the ongoing projects in the lab, get more experience in collecting data from human subjects, and administer experimental tasks and questionnaires. They also will be trained to collect data behaviorally and using the only Norway 7T MRI scanner. Analyses of imaging data require extensive training, and they will be given a chance to learn and implement some of this training on their data or already collected data. These skills are valuable for students who are aiming to continue their academic paths in the field of cognitive neuroscience and for clinicians to be able to gain a deeper understanding of neuroimaging methods.

More information: Please see lab website Maryam Ziaei - NTNU

Project description for STRAT-PARK (til Forskerlinjestudenter)

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease and a major cause of death and impairment with devastating global socioeconomic consequences. Available treatments are only symptomatic, and patients face a future of progressive disability. With a prevalence expected to double by 2040, there is an urgent need for understanding and treating PD. Currently, all efforts to develop neuroprotective therapies for PD is hampered by the clinical and biological heterogeneity of the disease. Although commonly referred as a single disease, PD presents a high variability in terms of age of onset, constellation and severity of clinical features, rate of progression, response to treatment, risk of complications, as well as in type, severity and distribution of underlying pathology. The basis for this diversity is assumed to reflect distinct underlying pathophysiological mechanisms opening possibility to investigate new biomarkers to stratify PD patients. As for now, observational studies and therapeutic trials are being conducted on highly heterogenous groups and represent a major obstacle in developing effective treatments.

Aims: The STRAT-PARK initiative is a multi-center longitudinal cohort aiming to stratify PD patients according to underlying biological mechanisms and develop biomarkers to enable stratification in clinical practice with the ultimate goal to develop and apply tailored treatments.

Methods: Participants included at one of the three study sites (St. Olav’s University Hospital, Haukeland University Hospital and the London Movement Disorders Centre in Ontario, Canada) undergo clinical examination annually, biosampling (blood sample, lumbar puncture and muscle biopsy) and advanced imaging (3T or 7T brain MRI) every second year. Molecular analyses include mitochondrial markers and multi-omics. Data will be analyzed using hypotheses-driven and agnostic approaches including artificial intelligence methods.

Main tasks: Participate in data collection and registration at St. Olav’s University Hospital, participate in data analyses and examine novel specific questions relating to PD progression and subtypes. Specific projects will be tailored to the candidate and will position the candidate for a full PhD project following completion of the Forskerlinje year.

Research group and mentors: The study is coordinated by Neuro-SysMed Center of Excellence for Clinical Treatment Research at Haukeland. Study director, Prof. Charalampos Tzoulis, is Director for Neurogeneration and CoDirector of the Neuro-SysMed Center and Head of the Neuromics lab at University of Bergen (UiB). In Trondheim, recruitment and follow-up is coordinated by PhD fellow and neurology resident Kjersti Eline Stige (kjersti.e.stige@ntnu.no) and senior researcher and neurology resident Thanh P. Doan (thanh.p.doan@ntnu.no) from the Neuroclinic, St. Olav’s University Hospital and Department of Neuromedicine and Movement Science, NTNU.

CAC-IBD - The Clinical Academic Group for Precision Medicine in Inflammatory Bowel Disease (IBD)

Background: Inflammatory bowel disease (IBD) are a group of chronic, relapsing inflammatory diseases that mostly are diagnosed at an early age and involves decades of active disease and treatment. Thus, care of patients with IBD is an important part of the activity of gastroenterology departments. A well-known problem in the clinic is that the course of the disease and the effect of treatments are very difficult to predict. This patient heterogeneity is also a challenge in IBD research.

Research projects and methods: Our research team has for years generated several biobanks with biological material and clinical and experimental data. We are currently collecting a particularly well-controlled and standardized 5 years longitudinal biobank for IBD (“IBDSelect”), including establishment of standardized diagnostics, follow-up, and treatment decision protocols for patients with IBD in the clinical practice at all participating departments. In addition, we have implemented patient-derived intestinal organoids (“mini-guts”) which are the most promising pre-clinical system for IBD-disease modelling and mechanistic analyses of IBD drugs. This material and data are used by the several members in CAG-IBD in a wide range of both advanced laboratory and clinical research projects, which all can include student projects. We focus on e.g., biomarkers, pro-inflammatory signaling mechanisms, microbiota (including virus)-host interactions, modes of action and drug-responses for approved and experimental drugs on an individual level, mucosal healing, histomorphometry and computational pathology, unconventional immune cells and effects of genetic and epigenetic background.

Aim: Together, the objectives of our projects are to understand disease mechanisms and pathobiology, predict treatment responses and disease course, clarify prognostic factors, and develop service innovations. The overall aim is to develop more individualized diagnosis, treatment, and care of patients with IBD and increase the quality of clinical practice.

The Clinical Academic Group for Precision medicine in IBD (CAG-IBD) is a major Regional Health Authority and University supported initiative that unites experienced clinicians and basic researchers across the university and gastroenterology departments (including pediatric) at Levanger, Molde and St. Olav’s Hospital into one joint group for patient-focused translational research on IBD (ulcerative colitis, Crohn’s disease, microscopic colitis) (https://www.ntnu.edu/cag-ibd/).

We are looking for 1-2 motivated students who are interested in the combination of basic research and clinical research, like to combine theoretical and practical laboratory work and are interested in continuing after Forskerlinjen with a PhD degree. All students will be an integrated part of our research team on a daily basis and receive all necessary training.

Contact for more information: Ingunn Bakke, Associate Professor, Department of Clinical and Molecular Medicine (IKOM), NTNU. Ingunn.bakke@ntnu.no

Transient global amnesia - a path to restore memory

Number of students: 1-3

Background: Episodic memory is the collection of past personal experiences that occurred at particular times and places. Such memories lie at the heart of our experience of the world around us and our ability to interact with it. This critical human ability falls apart in dementia, as seen in Alzheimer’s disease (AD). Episodic memory relies on a subset of structures within the medial temporal lobe (MTL) such as the hippocampus and entorhinal cortex. Their molecular, cellular, and circuit- level dynamics and how they break down in diseases, remains an area of intense investigation. However, important advances have been made in the field, such as the Nobel Prize awarded work from the Mosers and colleagues at the Kavli Institute for Systems Neuroscience at NTNU, which revealed key mechanisms of the brain’s navigational and episodic memory system. Transient global amnesia (TGA) is a particular disorder of episodic memory characterized by hyperacute anterograde and retrograde amnesia. Strikingly, this condition is entirely transitory. The acute amnestic phase lasts up to 24 hours, and magnetic resonance imaging (MRI) points to localized microstructural changes in the hippocampus. This brain region is also one of the first affected by AD. Following the acute phase, MRI findings and cognitive deficits normalize within two weeks. Full structural lesion reversion is unique to this condition and remains an enigma. TGA is therefore a reversible pathological process which provides an exceptional model of acute cognitive impairment onset and spontaneous recovery.

Aim: By establishing TGA as a model for reversible cognitive impairment, this study will leverage its unique stereotypic and concise course to characterize an unexplored continuum of biomarkers for cognitive impairment such as AD and offer new windows for diagnosis and therapeutic interventions.

Methods: Standard clinical diagnosis combined with advanced cognitive examinations in the emergency department. Advanced radiological methods such as ultra-high field structural, functional and spectroscopical MRI. State of the art systems, cognitive and translational neuroscience assays and data analysis.

Tasks (1) Diagnose TGA patients presenting with acute memory impairments, (2) perform comprehensive behavioral and cognitive test batteries, (3) provide assistance during advanced MRI examinations, (4) acquire basic knowledge of clinical neurology, neuroanatomy and neuroradiology and (5) participate in analysis of cognitive and imaging data.

Research student thesis: The dataset may be used to write 3 papers and possibly extended towards a PhD after completion of the medical studies.

Research group and mentors: The study is a collaboration between the department of Neurology at St.Olavs Hospital, INB and the Kavli Institute for Systems Neuroscience at NTNU led by Senior Researcher and clinician Thanh P. Doan (thanh.p.doan@ntnu.no) and Ass. Professor Tobias Navarro Schröder (t.navarroschroeder@ntnu.no). Together with their extensive professional network, the student will be in a unique environment to develop translational research in the clinic at the highest international standards.

Study neuronal-glial communication through various molecular tools

Background. Research on glial cells has not been prioritized since glia were first recognized as supportive cells – the glue - of the central nervous system (CNS). Thus, our know knowledge about glia lags almost a century behind that of neurons. Accumulating evidence in the recent decade elucidates that the glia tightly engage functionally with neurons within cortical circuits. Various research studies have demonstrated glial modulatory functions at the synaptic level as well as at the level of neuronal networks and behaviour. The concept of tripartite synapses has been introduced, indicating a unit of tri-archy synaptic structure. This definition of tripartite synapses anatomically stresses the third-party participation of glial processes in contrast to the traditional model of two-component neuronal synapses (pre- and post-synaptic neuronal components). Thus, the study of neuronal-glial communication is now brought to a new level.

Although plenty available data have already been encountered pointing to the importance of neuronal-glial cross-talk due to the complexity of brain circuits, the lack of study tools has hampered progress in the field. It cannot be denied that the limitations of current technologies would be a source of distortion for us to misunderstand the authentic details from such a complex network image. The research field nowadays is urging more advanced and combined cutting-edge tools allowing us to enter the realm of neuronal-glial interaction. Recently it has become possible to image as well as manipulate brain circuit function using optical tools. The application of optogenetics is the most inclined path for artificial stimulation and inhibition of neuronal activities, thereby to further explore their correlation with certain behaviours. Employing this method has been a great success and has revolutionized our understanding of the workings of the brain. Meanwhile, genetically encoded Ca2+ indicators (GECIs) combined with two-photon microscopy have played a significant role in monitoring live cell activities, especially in intact brains of living animals.

Objectives. The main objective of this project is to apply various molecular tools to study neuronal-glial interaction with two-photon imaging, such as optogenetic and chemogenetic tools.

The project has two secondary aims://

Aim 1. To test the developed method in two-photon imaging in mice.

Aim 2. To apply the suitable tool in two-photon imaging in mice.

Methods. This project involves following techniques: DNA cloning, rAAV production, immunohistochemistry and confocal microscopy, animal handling and behavior, in vivo / ex vivo two-photon imaging.

We are looking for highly motivated, well-organized and self-disciplined students who are interested in broadening their research knowledge in molecular and neuroscience fields and are interested in animal related work. For animal related experiments, students are mandatory to take the course “Laboratory Animal Science” for getting the animal working licence.

Contact information. Wannan Tang; wannan.tang@ntnu.no; Department of Clinical and Molecular Medicine, NTNU

Targeting astroglia-neuron interactions for developing mechanistic epilepsy therapies

Supervisor: Prof Emre Yaksi ( www.yaksilab.com )

Host institute: Kavli Institute for Systems Neuroscience, NTNU

Project description: 30% of 30000 epilepsy patients in Norway do not respond to available pharmacological therapies. Hence, there is a tremendous need for developing novel anti-seizure therapies. A promising new path to develop novel anti-seizure therapies relies on understanding the mechanistic causes of seizures and target those specific mechanisms. To date, mechanistic investigations of seizures have mostly focused on neurons. Despite this focus on the neural aspects of seizures, the largest fraction of non-neural cells of the brain, namely the astroglia, was kept in the background. While epilepsy patients shows astroglail abnormalities, the mechanisms linking astroglia to seizures is not understood. Our published results in zebrafish seizure and epilepsy models highlight an important role for the astroglial glutamate transporters and gap junctions in seizure generation and spread. In this project, the successful candidate will use high-throughput in vivo drugs screens targeting astroglia-neuron interactions in zebrafish seizure/epilepsy models, to identify novel anti-seizure approaches. The successful candidate will also perform functional brain imaging to test the impact of specific genetic and pharmacological perturbations of astroglia biology in seizure susceptibility. Combined with the advantage of zebrafish for performing high-throughput physiological and behavioral experiments, this approach has a great potential to identify key genetic and pharmacological targets to interfere with generation and spread of seizures.

Description of the host laboratory: The Yaksi lab is combining state of the art tools of neural circuit research to study how brain circuits function in health and in disease. Our multi-disciplinary lab is composed of life-scientists, medical doctors/students, engineers, and we interact with neurology clinics at St Olav and few other hospitals (Gent-Belgium, Istanbul-Turkey). This environment provides ample opportunity for Forskerlinje Medical Students to get involved in high quality biomedical research, combine their medical training with state-of-the-art technologies and questions, and learn several new methods, such as genetic tools, programming, functional brain imaging, neurophysiology, and behavioral video monitoring. At our lab, so far, all our completed Forskerlinje students have co-authored in around 1-3 high-quality publications, depending on their commitments to their projects and their collaborations with other lab member. Moreover, several of our Forskerlinje students, will be continuing their research at our lab, to obtain their PhD degrees.

Contact: If you are interested to learn more about this project, or other ongoing research at our lab, you may visit our labs website ( www.yaksilab.com ) and write an email to emre.yaksi@ntnu.no

Kardiovaskulær helse, legemiddelbruk og hjernehelse i et livsløpsperspektiv

Bakgrunn: Hjernehelse er et relativt nytt konsept som omfatter både mental og kognitiv helse. God mental og kognitiv helse er avgjørende for livskvalitet og samfunnsdeltakelse. Nyere forskning gir støtte til at god kardiovaskulær helse har sammenheng med god hjernehelse. Den observerte nedgangen idødeligheten av hjerte- og karsykdommer fra 1970 -tallet tilskrives både primær - og sekundærforebyggende tiltak, medikamentelle så vel som ikke-medikamentelle. Ifølge tall fra Folkehelseinstituttet bruker nær 1,2 millioner nordmenn legemidler for å forebygge eller behandle hjerte- og karsykdom. Vi vet samtidig mindre om samspillet mellom kardiovaskulær helse og hjernehelse i et livsløpsperspektiv, og i hvilken grad forholdet mellom helseadferd og legemiddelbruk påvirker sammenhengen mellom hjerte – og hjernehelse. I dette prosjektet benytter vi allerede innsamlede data fra Helseundersøkelsen i Trøndelag (HUNT) som er sammenstillet med data fra Reseptregisteret. HUNT er en stor, norsk befolkningsbasert helseundersøkelse som omfatter helseopplysninger og biologisk materiale fra innbyggerne i Trøndelag. Siden den første innsamlingsrunden i 1984 (HUNT1) har 240 000 trøndere deltatt. HUNT4 ble avsluttet i 2019 og HUNT representerer dermed et unikt materiale for å studere befolkningens helse i et livsløpsperspektiv.

Metode: Epidemiologisk forskning med bruk av data om kardiovaskulær – og kognitiv helse, helseadferd og legemiddelbruk (kardiovaskulære legemidler samt psykofarmaka og kolinesterasehemmere).

Mål: Å studere hvorvidt samspillet mellom helseadferd og legemiddelbruk har sammenheng med mental og kognitiv helse

Vi er på jakt etter motiverte forskjerlinjestudenter som ønsker å lære seg epidemiologisk forskning med relevante problemstillinger som faller inn under prosjektets målsetting og som ender ut i 1-2 publiserte vitenskapelige artikler. Presisering og avgrensning av forskningsspørsmål vil skje i samarbeid med hoved – og biveiledere. Forskerlinjestudenten (e) vil være tilknyttet fagenheten Folkehelse og samfunnsmedisin ved Institutt for Samfunnsmedisin og sykepleie (ISM), NTNU. Forskergruppen består av stipendiater, masterstudenter og forskere fra NTNU i tillegg til regionale, nasjonale og internasjonale samarbeidspartnere.

Kontaktinformasjon:

Førsteamanuensis Linda Ernstsen, ISM: linda.ernstsen@ntnu.no, tlf: 73 413036

Alzheimer’s disease in a dish

Alzheimer’s disease (AD) accounts for 60-70% of all dementia cases and is the most common neurodegenerative disorder. Affected individuals are clinically characterized by a progressive impairment of behavioral and cognitive functions including memory, language, attention, and judgement. The major histopathological hallmarks are extracellular deposited β-amyloid (Aβ) plaques derived from amyloid precursor protein (APP) and intracellular accumulated neurofibrillary tangles. Mutations in APP and presenilin genes accelerating Aβ production cause early-onset familiar forms of AD, accounting for less than 5% of total cases. The vast majority of 95% of AD patients have sporadic forms featuring late onset age 65 or older with no clearly identified etiology. Nearly 36 million people worldwide suffer from AD and this number is expected to triple by 2050. There is an urgent economic and social need for a treatment of AD, however no therapeutics are available that will stop or delay development of the disease. More than 200 clinical trials failed or have been abandoned in the last decade. Probable explanations include late initiation of treatments because of challenging diagnosis at early stages and inadequate understanding of the complex pathophysiology of AD.
In this project, we aim to address these challenges by establishing a platform for patient-derived cell models to reveal molecular pathways of neurodegeneration as a basis for identifying early biomarkers and a path towards a cure for AD. Various state-of-the-art methods will be applied including isolation of blood cells, stem cell reprogramming, generating and culturing of human brain organoids, epigenetic profiling and immunofluorescence staining. The student will also have the possibility to participate in the clinical examination of research study participants together with experienced neurologists.
For more information please contact:
Associate Prof. Katja Scheffler,
Department of Neuromedicine and Movement Science, NTNU and Department of Neurology, St. Olavs Hospital
email: katja.scheffler@ntnu.no
https://www.ntnu.edu/inb/tronderbrain
https://www.ntnu.edu/inb/neurobio

Profiling epigenetic landscapes in glioblastoma: Implications for novel diagnostics and treatment

Glioblastoma multiforme (GBM) is the most common aggressive malignant brain tumor, characterized by a poor prognosis with a survival rate of 5-10% at five years. The broad inter- and intra-tumoral heterogeneous nature of GBM is a major challenge for current standard care, resulting in high rate of tumor recurrence and poor outcomes. Hence, there is an urgent need to develop novel strategies for diagnosis and treatment of the disease that improve the life quality of patients, e.g., cure cancer, prolong life span, and reduce collateral effects. Epigenetic alterations are of high significance in GBM as they act as quantifiable biomarkers for the optimum stratification of patients. And epigenetic perturbation of pivotal gene expression is a hallmark in cancer pathologies. However, the precise epigenetic mechanisms underlying GBM development and progression remain largely unknown. The epigenetic-based therapeutic approaches in GBM treatment merit further investigation.

In this project, we will use patient derived glioblastoma organoids (PD-GBO) and state-of-the-art technologies to resolve the heterogeneity of epigenetic DNA and histone modifications among distinct GBM cell populations, and to understand epigenetic mechanisms underlying GBM progression. This project will (i) identify novel epigenetic signatures as biomarkers defining the heterogeneity of PD-GBO, (ii) provide enormous patient-specific epigenetic data to advance our knowledge on the epigenetic regulation of GBM pathogenesis, (iii) discover novel epigenetic drugs and combined therapeutic approaches in GBM treatment, (iv) develop innovative strategies for the personalized GBM therapy, and (v) establish new methodologies and workflows to improve the epigenetic-based diagnostics and treatment in cancer types beyond GBM. This is a preclinical study for drug discovery, aiming at further implementation to clinical trials in patients.

This project is based on the hypotheses that (i) the heterogeneity of epigenetic DNA and histone modifications in different cell populations accounts for the diversity of GBM pathologies; (ii) understanding mutually reinforced epigenetic mechanisms (e.g., DNA methylation and demethylation,
histone modifications) in distinct PD-GBO will lead to the development of novel prognostic markers, therapeutic targets, and new treatment modalities that are customized for individual GBM patients.
The primary objective of the project is to reveal novel epigenetic targets and mechanisms underlying the progression and heterogeneity of distinct PD-GBO, as well as their therapeutic potential in GBM diagnostics and treatment.

Secondary objectives are:
1) Generate, characterize and biobank PD-GBO as preclinical models for GBM.
2) Identify novel epigenetic signatures defining the heterogeneity of PD-GBO.
3) Reveal specific epigenetic mechanisms underlying the progression of distinct PD-GBO.
4) Discover novel epigenetic drugs and combined therapeutic approaches in GBM treatment

This project will implement various methodologies, including (i) generation and biobanking of patient derived GBM organoids (PD-GBO); (ii) pathological analysis of PD-GBO using advanced confocal microscopy and tools for 3D image analysis; (iii) optimized tissue dissociation and cell isolation method for PD-GBO; (iv) cutting-edge sequencing technologies to profile DNA cytosine modifications and histone modifications in PD-GBO; (v) RNA and protein analysis to elucidate new molecular targets and underlying mechanisms in GBM pathology.

We are looking for highly motivated, well-organized, and self-disciplined students who express enthusiasm to combine basic and clinical research.

Contact persons: Jing Ye (main supervisor), jing.ye@ntnu.no
Magnar Bjørås(co-supervisor), magnar.bjoras@ntnu.no
Department of Clinical and Molecular Medicine (IKOM), NTNU

TGF-β family signaling in cancer

Multiple myeloma is a cancer arising in the antibody-producing plasma cells that are in the bone marrow. The malignant cells disturb the balance between bone forming and bone degrading cells, leading to bone disease in most patients. Despite recent advances in drug development, myeloma is regarded incurable, thus there is a need for novel treatments.

ALK2 (encoded by ACVR1) is a receptor for bone morphogenetic proteins (BMP), a group of endogenous signaling molecules that can either kill the myeloma cells or keep them dormant. Activation of ALK2 leads to phosphorylation of SMAD transcription factors, which in turn downregulate c-MYC, an important oncogene in myeloma cells. We are interested in regulation of ALK2 activity, and we have several ongoing projects related to this. Specifically, we have a project on targeting an inhibitory protein named FKBP12 using non-immunosuppressive compounds. Targeting FKBP12 leads to a huge potentiation of the ALK2 activity and thereby increases cell death. Another project is focused on comparing different phosphoproteins downstream of different BMP ligands to further characterize how signaling molecules (other than the SMADs) contribute to BMP-induced cell death. A third project involves a CRISPR/Cas6 whole genome screen to identify new factors that either influence ALK2 regulation or execution of apoptosis downstream of activated SMADs. We also work on endoglin (soluble and membrane-bound) and BMP9 and how they affect signaling via ALK2.

We look for students that are interested in contributing to these projects. The projects require a lot of laboratory work. Typical methods that will be used are cultivation of myeloma cell lines and other cell types, western blotting, quantitative RT-PCR, ELISA, flow cytometry, CRISPR/Cas9 or siRNA transfections, as well as assays for cell proliferation and cell death. Our research group is part of the Clinical Academic Group (CAG) “Multiple myeloma in Central Norway” and we have weekly scientific meetings with other myeloma research groups. We have access to patient samples from Biobank1 when this is needed for projects, and we also collaborate with the Dep. of Hematology, St. Olavs Hospital and the Nordic Myeloma Study Group to get access to patient material from clinical trials.

We are located at the Laboratory Center and Gastro Center, campus Øya. There is one medical research student and one PhD student in the group (+ one more being recruited) and we regularly have master- or bachelor students in the lab.

Contact information:

Toril Holien, Associate Professor, Dep. of Biomedical Laboratory Science, Faculty of Natural Sciences and Research adviser, Dep. of Immunology and Transfusion Medicine, St. Olavs Hospital. toril.holien@ntnu.no

Neurocognitive mechanisms of stress and anxiety in aging

Number of students wanted: 1-2

Main supervisor (your name and contact information): Associate Professor Maryam ZiaeiEmail: maryam.ziaei@ntnu.no

Background and Objectives: Despite the cognitive decline, social and emotional aspects of aging are preserved or even increased with aging. A growing body of neuroimaging and behavioral studies suggests that aging is associated with preserved or even enhanced emotional responses to positive emotions/positive feedback, reward expectation, and with calming of the negative emotions, negative feedback, and punishment. Positive emotions help buffer against stress and help individuals to bounce back from stressful experiences and thus are valuable tools for establishing enhanced outcomes in well-being. Given that age-related shifts in motivational processes have profound consequences for cognitive and social functions, an important question arises how these emotional and motivational changes in aging contribute to stress resilience among older adults. In my lab, we investigate behavioral and neurocognitive mechanisms underlying stress and resilience, with the question that why some individuals succumb to depression and anxiety and some individuals show more reserved that help to explain changes in behavioral outcome.

Methods: We use a variety of methods such as behavioral and neuroimaging techniques to investigate behavioral, structural, and functional changes related to social and emotional processes in aging. We use functional magnetic resonance imaging (fMRI) to measure brain activity associated with a cognitive task implemented in the scanner. We also measure structural volumes and integrity of brain regions using structural MRI. Additionally, we use daily life sampling of emotional experience to ascertain a link between lab-based performance and real-life experiences across the life span.

Student requirements: Students are given a chance of getting involved in the ongoing projects in the lab, get more experience in collecting data from human subjects, and administer experimental tasks and questionnaires. They also will be trained to collect data behaviorally and using MRI machines. Analyses of imaging data require extensive training, and they will be given a chance to learn and implement some of this training on their data or already collected data. These skills are valuable for students who are aiming to continue their academic paths in the field of cognitive neuroscience.

More information: Please see lab website

Digital samhandling om personer med store og sammensatte behov

Personer med komplekse behov er den gruppen pasienter/brukere som alle tjenestene er i kontakt med, men som ingen av tjenestene kan ta ansvar for alene. Det er personer som på grunn av helsemessige eller sosiale forhold har behov for hjelp fra flere spesialiserte tjenester og som har begrensede forutsetninger for å ivareta egne behov. Dette er også de personen som har størst behov for helsetjenestens ressurser, og de finnes blant de 5% som har behov for 50% av ressursene målt i forbruk. Disse pasientene blir ikke «friske». Målet er å holde de på høyest mulig mestrings og funksjonsnivå over tid.

I forskningsprosjektet «DignityCare» skal det studeres hva som gjøres for å gi helhetlige og koordinerte tjenester til personer med komplekse behov i arbeidet med å realisere «En innbygger - En journal». Det skal gjøres ved bl.a. å følge og sammenligne arbeidet i Helseplattformen i Helse-Midt-Norge og hvordan den nasjonale arbeidet gjøres i Helse Nord, samt utvikle en digital løsning for samhandling innenfor disse områdene. Forskerne vil følge prosessene og fortløpende gi innspill underveis om det man finner (aksjonsforskning). Forskernes hypotese er at personer med komplekse behov er de som vil ha størst nytte av et helhetlig digital samhandling på tvers av tjenestene. Ved å lage løsninger som fungerer for disse, vil man lage løsninger som bidrar til bedre samhandling og koordinering også for andre, inkludert bedre tjenester og ressursutnyttelse.

I DignityCare prosjektet er det mulighet for ulike prosjekt for en forskerlinjestudent med interesse for e-helse og samhandling.

Dette prosjektet vil være innenfor forskningsgruppen for helsetjenesteforskning ved Institutt for Samfunnsmedisin og Sykepleie (ISM). Veileder vil være Aslak Steinsbekk, Professor i Medisinske atferdsfag og Helsetjenesteforskning og Professor II ved Nasjonalt senter for e-helseforskning, Tlf: 73 59 75 74, E-post: aslak.steinsbekk@ntnu.no

HUNT og utvikling i bruk av alternativ behandling

En relativt stor andel av befolkningen bruker alternativ behandling som akupunktur, homeopati mm. Det gjør det viktig å ha kunnskap om denne gruppen. HUNT har hatt med et eget spørreskjema i både HUNT 3 og 4, samt hatt spørsmål om alternativ behandling i de andre undersøkelsene. Dette er et unikt datamateriale i verdenssammenheng for å studere utvikling i bruk av alternativ medisin over lang tid. Innenfor dette overordnede tema er det mulig å velge ut ulike problemstillinger, for eksempel å se på bestemte pasientgrupper, sammenligning med annen helsetjenestebruk og koble på registerdata om sykelighet og dødelighet for å sammenligne utkomme mellom de som bruker alternativ behandling og de som ikke har gjort det.
Dette prosjektet vil være innenfor forskningsgruppen for helsetjenesteforskning ved Institutt for Samfunnsmedisin og Sykepleie (ISM). Veileder vil være Aslak Steinsbekk, Professor i Medisinske atferdsfag og Helsetjenesteforskning og Professor II ved Nasjonalt senter for e-helseforskning, Tlf: 73 59 75 74, E-post: aslak.steinsbekk@ntnu.no

Rehabilitation of stroke patients

Background
Stroke care requires more bed days in hospitals and rehabilitation facilities than most other somatic illnesses. This problem is set to increase significantly with an aging population. It is therefore a growing need to improve stroke rehabilitation that aims to improve functional neurological outcome after stroke.

Aims
This project aims to develop patient-specific stroke rehabilitation based on a detailed multiparametric assessment of the functional neural network after the brain damage. This assessment will be used to design a personalized rehabilitation program in which the patients will train restoration of motor functions while both muscle and brain activities are registered and quantified with electroencephalogram and electromyography.

Methods
Different magnetic resonance imaging (MRI) protocols will assess the degree of brain damage and quantify the surviving functional brain tissue. Patient-specific rehabilitation will use this knowledge to train motor-function. EEG, EMG, and degree of improvement in movement will be quantified using advanced 3-dimensional kinematic video analysis.

Tasks
• Assist in the reqruitment of patients in close collaboration with the stroke unit, St Olavs hospital
• Documentation of degree of brain damage correlated with neurological assessments of motorfunction
• Use EEG, EMG and kinematic video equipment during training of motor functions.
• Analysis of data

Results
We aim to publish 1-2 articles based on results from the project. Furthermore, it will be possible to extend the project towards a PhD after completion of the medical studies.

Who to contact Axel Sandvig; axel.sandvig@ntnu.no, Institute for Neuromedicine and movement science, NTNU. Hanne Ellekjær; Hanne.Ellekjer@stolav.no; Institute for Neuromedicine and movement science NTNU and Stroke Unit, St.Olavs hospital

Sleep better to feel better

Sleep is a fundamental human need with large impact on both psychological and somatic health. However, for patients with mental disorders, sleep is often disturbed. Across all diagnostic groups, sleep disturbance is one of the most common and disruptive symptoms. For decades, it has been assumed that the sleep disturbance these patients experience was a secondary symptom of a primary mental disorder, but recently this has changed. Experimental and clinical data now suggest that there is a reciprocal relationship between sleep disturbance and mental disorders where they perpetuate and aggravate each other. This makes sleep disturbance a potential therapeutic target in the treatment of mental disorders.

Evidence emerging the last decade indicate that providing Cognitive Behavior Therapy for Insomnia (CBT-I) to patients with mental disorders not only improves sleep, but also has clinically meaningful effects on their primary mental disorder. However, a major problem has been disseminating CBT-I and few therapists are trained in this intervention. Consequently, most patients receive sleep medication although evidence clearly indicate that CBT-I is more effective and should be the treatment of choice. In Norway 7% of the general population are prescribed hypnotics each year, with numbers likely to be higher in mental health care. As demand for CBT-I exceeds supply, a fully automated digital version of CBT-I (dCBT-I) has been developed that has been shown to be remarkably effective.

In three ongoing multicenter randomized controlled trials, we will test if this dCBT-I can be used to treat a large number of patients. The first trial is for patients who are on the wait list to receive ordinary outpatient treatment in community mental health care clinics. The second trial is for patients referred to specialist outpatient treatment for alcohol use disorder. The third trial is for individuals with Multiple Sclerosis. Main outcomes in the trials will be assessed using patient self-report and official health registers. By focusing on improving sleep early in the course of treatment, using a digital treatment, these trials represent a novel method of delivering mental health care services which could improve treatment quality and use of resources.

The candidate will be included in the Sleep and Circadian Rhythms Research group, lead by Håvard Kallestad, PhD. The research group is integrated with the sleep clinic and acute ward at Østmarka, lead by Knut Langsrud. The research group has conducted several other randomized controlled clinical trials testing the effectiveness of interventions that act on sleep and the circadian system in individuals with mental disorders and in the general population. The candidate will participate in data collection of the ongoing trials and will be able to write research papers from this or the other clinical trials that have been conducted in the research group.

Contact info: Project coordinator, Simen Berg Saksvik, simen.b.saksvik@ntnu.no

Personalized cancer treatment by developing integrated MR methods and data analysis tools for functional and molecular assessment of tumors

The MR Cancer group (http://www.ntnu.edu/isb/mr-cancer) studies functional and metabolic properties of cancer using both MR imaging and MR spectroscopic technologies. Our long-term objective is to improve and individualize cancer treatment by developing integrated MR methods and data analysis tools for functional and molecular assessment of tumors. We use a broad spectrum of systems for cancer studies, spanning from cultured cancer cells to humans, and have access to dedicated MR equipment for in vitro, ex vivo, preclinical and clinical research.

We have several large ongoing research projects supported by The Research council of Norway, the Norwegian Cancer Society and regional health authorities, and we can offer students tailored projects in line with their main interests.

For further information, please contact:Prof. Tone F. Bathen (95021097, tone.f.bathen@ntnu.no)

Respiratory virus in children with airway infections

Background: Children have on average six respiratory tract infections (RTI) each year. The majority are mild infections in upper airways, but some may involve lower airways, leading to more severe manifestations and need of hospitalization. In well-vaccinated children, the rate of bacterial RTIs have decreased, whereas the causative impact of viruses is likely to have increased. Recent years, new airway viruses have been detected. As an example, human metapneumonivirus was detected in 2002. We have previous ly studied the incidence and clinical manifestations of this virus among children hospitalized at St. Olavs hospital.

Aim: We aim to describe the burden of human metapneumovirus lower airway infections in children in Norway.

Methods: We will use a dataset from the NOREPIS study comprising nearly 3000 children enrolled from November 2015 to May 2018 at five Norwegian hospitals due to cough, fever, and other signs of respiratory infections. These 5 hospitals care for approximately 40% of Norwegian children. Parents to all children contended to participation. We include children < 5 years old among who 243 had HMPV, and 1090 had RSV. All children were sampled with a nasopharyngeal swap. Swaps were analyzed at each hospital laboratories using various polymerase chain reaction (PCR) test methods. Clinical information was collected.

The task is 1) to re-test all HMPV positive samples and a random selected group of comparable number with RSV, using in-house TaqMan real-time PCR assays, and to genotype HMPV-positive specimens by real-time PCR and DNA sequencing using primers targeting the F-gene of HMPV. 2) to calculate incidence rates of human metapneumovirus lower airway infections in children < 5 years old, and 3) describe clinical manifestations, risk factors and outcome compared to RSV.

Research student thesis: The dataset may be used to write 3 papers.

Research group and mentors: The study is a part of the studies in the CAIR-group. Mentors will be associate professor Andreas Christensen and professor Henrik Døllner, IKOM.

Informasjon

For å få vite mer om forskerlinjestudiet og hvordan finne prosjekt/veileder, ta kontakt med faglig leder for forskerlinjen, professor Pål Richard Romundstad, eller Cicilie Nordvik==

Vi anbefaler også å ta kontakt med forskerlinjestudentene selv gjennom studentenes egen linjeforening, Signifikant.