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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.

Table of Contents [-]

  1. Development of a Smartphone Based Screening Tool for Neonatal Jaundice
  2. InnaTe-HIV: Implications of innate immune activation of T-cells in HIV infection
  3. Spennende tverrfaglig studie i skjæringspunktet mellom obstetrikk og basalmedisin: Metformin-effect on serum cytokine profile in pregnant women with PCOS and their offspring
  4. Before the Beginning – Breaking the intergenerational cycle of cardiometabolic disease by preconception lifestyle interventions.
  5. Population models of Retinopathy of Prematurity
  6.  \\Human bocavirus and other virus in children with airway infections
  7. Artificial Pancreas Trondheim (APT)
  8. Development of novel myeloma drugs
  9. Quality of life in adults born with low birth weight and associations with cognition, mental and physical health and cerebral MRI
  10. Global health
  11. Svangerskapsdiabetes
  12.  Analinkontinens
  13. Circulating tumor DNA as a biomarker in multiple myeloma
  14. Studying the function of brain circuits in helath and disease
  15. Impact of oxidative DNA damage repair on cognitive aging   
  16. Impact of PARylation on cognition and neurodegeneration
  17. Tackling drug resistance in multiple myeloma
  18. Fremtidens Operasjonsrom
  19. Hunt Longitudinal Ankylosing spondylitis and Rheumatoid arthritis Study - HuLARS
  20. Forekomst av motonevronsykdommer i Midt-Norge
  21. Physical Activity, Vitamin D and Bone Health
  22. KOLS – hva predikerer helsestatus og behandlingsbehov?
  23. EBBA-II studien (Energy Balance and Breast Cancer Aspects)
  24. Virus infection and corticosteroid treatments in asthma and chronic obstructive pulmonary disease
  25. Brystkreft
  26. The role of motile cilia in sensory coding and neurological diseases  
  27. Beskytter osteoporose mot kreft?
  28. Correlative microscopy, combining confocal, multifoton imaging and electron microscopic analysis at the nanoscale
  29. Prognostiske faktorer i hjernesvulster
  30. Forskning på cerebral parese
  31. Helsetjenesteforskning  
  32. For å få vite mer om forskerlinjestudiet og hvordan finne prosjekt/veileder, ta kontakt med http://www.ntnu.no/ansatte/anna.bofinfaglig leder for forskerlinjen, professor Anna Bofin, eller http://www.ntnu.no/ansatte/may.k.dyrendahlstudiekonsulent May Karin Dyrendahl.

Development of a Smartphone Based Screening Tool for Neonatal Jaundice #

Neonatal jaundice is a common condition among newborns, affecting 60-80 of all newborns. The condition is caused by elevated levels of bilirubin, hyperbilirubinemia, and although most cases are harmless and self-limiting, untreated severe jaundice could cause brain damage or even be fatal. Worldwide, more than 100.000 newborns die every year due to hyperbilirubinemia.

The current approach of visual inspection to detect neonatal jaundice is ineffective, and involves a high risk of missing cases of severe jaundice. Current alternatives are expensive, limiting the distribution and accessibility. There is thus an urgent need for more effective and accessible approaches for timely recognition of clinical relevant jaundice.

We have developed a novel color calibration card and a screening tool and that can run on a regular smartphone. By taking images of the newborn skin with the color calibration card in the image, we can perform color analysis that is translated to bilirubin estimates. The color calibration card makes it possible to adjust for different light conditions as well as for potential differences between phones.

This tool has been tested in trials in Norway and Mexico, and currently a trial in Surabaya, Indonesia is ongoing. Further trials in Nepal, Tanzania and the Netherlands are under planning.

This project is the result of interdisciplinary cooperation at NTNU. It has led to the foundation of a spin-off start-up company, Picterus AS, that the student will work closely with. Development and implementation of this new tool opens a wide range of opportunities for student, both in Norway and abroad. This include among others:

  • Further studies on the technology, either bio-optics or software 
  • Further clinical trials in new populations 
  • Implementation studies 
  • User experience studies 
  • Development and evaluation of teaching material/course on neonatal jaundice 
  • Studies on potential impact of this tool, both on health outcome as well as health economics
  • Studies on mobile health in low resource settings 
  • Investigation on potential other uses of the technology

The goal is to develop a low-cost, easy-to-use and accurate bilirubin estimator, and to implement this tool in a way that ensure sustainability.

If you find this project interesting, please contact Anders Aune, MD PhD Candidate, MH/ISM

 

InnaTe-HIV: Implications of innate immune activation of T-cells in HIV infection #

Prosjektet fokuserer på betydningen av inflammasjon ved HIV og identifisering av nye faktorer i vertscellene som HIV trenger for å etablere infeksjon. Takket være anti-retroviral behandling (ART) så kan pasienter i dag leve et tilnærmet normalt liv med HIV uten å utvikle dødelig AIDS sykdom. Likevel ses komplikasjoner som følge av lang tids behandling med ART, blant annet økt risiko for hjerte-kar sykdom, nyre- og leversykdom, nevrologiske problemer og annet. Dette kan skyldes for tidlig aldring av immunsystemet, så kalt "inflamm-aging" som antakelig er forårsaket av lavgradig, kronisk inflammasjon hos HIV pasienter. Opphavet kan være reservoar av virus og/eller lekkasje av bakterier fra tarm, men dette er ikke kjent. I dette prosjektet studerer vi HIV infeksjon i cellekulturer. Vi studerer hvordan T cellene responderer på HIV infeksjon (inflammasjonsrespons, differensiering, celledød), og vi har gjort en stor CRISPR/Cas9 screen i T celler for å identifisere gener som er sentrale i HIV-infeksjon. Screenet er gjort i samarbeid med forskningsgruppen til Richard Kandasamy v CEMIR, og vi har en rekke kandidat-gener som vi nå skal følge opp eksperimentelt for å se hvilken rolle de har under HIV infeksjon. Forskerlinjeoppgaven vil tilpasses den enkeltes interesser, men vi ønsker en student som er motivert for å jobbe i labben sammen med de andre prosjektdeltakerne (som også vil fungere som medveiledere).

 Forskningsgruppa til Trude Flo studerer mykobakterie- og HIV infeksjon: immunmekanismer som aktiveres og virker mot mykobakterier og HIV, og hvilke virulensstrategier mikrobene bruker for å omgå disse og etablere infeksjon. Forskningsgruppa består av ca 10-12 personer og er en del av CEMIR, et senter for fremragende forskning ved MH fakultetet der Flo også er nestleder. CEMIR huser over 80 ansatte fra 15 forskjellige land, og det er en flott mulighet for en forskerspire å tilegne seg bred erfaring og kunnskap innen inflammasjon, cellebiologi og immunologi. 

Kontaktpersoner: prosjektleder Trude Flo,  forsker Markus Haug eller post doktor Hany Meås

 

Spennende tverrfaglig studie i skjæringspunktet mellom obstetrikk og basalmedisin: Metformin-effect on serum cytokine profile in pregnant women with PCOS and their offspring #

Background: Polycystisk ovariesyndrom (PCOS) affects some 10-15% of women in reproductive age.  The cornerstones of PCOS are insulin resistance and hyperandrogenism. Common symptoms are oligo-amenorrhea, hirsutism and acne. PCOS has implications both for fertility and pregnancy outcome. There is evidence for increased prevalence of inflammatory pregnancy complications, such as gestational diabetes, preeclampsia and preterm delivery. PCOS is closely associated to obesity, type 2 diabetes and cardiovascular disease. All these conditions are characterized by increased inflammatory processes.
We have shown that metformin reduces the risk of late miscarriage and preterm birth. We do however not know the mechanism of this finding; one theory is that metformin may alter the inflammatory status in pregnancy. 

Project description:
The present study comprises serum samples from more than 700 women with PCOS through pregnancy. The women were randomized to metformin or placebo. The aim of the study is to characterize the serum profile of 27 cytokines during pregnancy in these women.
Study questions:
Does metformin affect the cytokine pattern in pregnant women with PCOS? If yes, in which manner? Does intrauterine metformin exposure change the inflammatory profile of the offspring?

Our research group is internationally acknowledged, we publish in high-ranked journals and have long experience of supervising/mentoring. The project involves use of multivariate statistical methods. We are looking for a dedicated and curious student who likes both to work in group and individually. Eszter Vanky (IKOM) and Ann-Charlotte Iversen (CEMIR). Contact: eszter.vanky@ntnu.no

 

Before the Beginning – Breaking the intergenerational cycle of cardiometabolic disease by preconception lifestyle interventions. #

Maternal obesity and hyperglycaemia in pregnancy increase the long-term health risk for both mother and child, leading to an intergenerational cycle of cardiometabolic disease. Current lifestyle interventions typically start in the second trimester and have limited efficacy. Our hypothesis is that the pre-existing metabolic profile of future mothers needs to improve preconception to confer health benefits for mother and child. In this translational-clinical project, we aim to discover how improving maternal preconception health will influence the cardiometabolic health of the mother during pregnancy and of the offspring. To reach these goals, we will determine the effects of two interventions: 1) time-restricted feeding (TRF) and 2) high intensity interval training (HIT), both of which rapidly improve glycaemic control. TRF, in which food intake is confined to <10 h of the day without a deliberate reduction in energy intake, reduces adiposity and improves glycaemic control in animal models and in humans. HIT is time-efficient and enjoyable and involves short bursts of intense exercise separated by rest breaks. Our preliminary data shows that HIT is safe for the mother and foetus. In the first phase, women at risk of gestational diabetes who are planning a pregnancy will undergo TRF and HIT, before and throughout pregnancy. In parallel, using diet-induced obese rats, we will determine the isolated and combined effects of these interventions on adult offspring cardiometabolic health. In the second phase, we will identify underlying mechanisms for the effects of HIT and TRF for mothers and offspring. Our aim is to establish an optimal prevention strategy to improve maternal preconception and gestational health, therefore reducing the risk of cardiometabolic diseases in the future generations. This conceptual shift in maternal care provides a platform for improved health outcomes for mother and offspring, breaking the intergenerational cycle of cardiometabolic disorders.

 Forskerlinje-oppgave knyttet til dette prosjektet:

Vi vil gjerne ha med oss en forskerlinjestudent på laget. Som student vil du kunne jobbe med enten den humane studien og/eller med dyre-eksperimentene. For mer informasjon, kontakt: Trine Moholdt, Forsker, Institutt for sirkulasjon og bildediagnostikk

 

Population models of Retinopathy of Prematurity #

 A common visual disorder in the preterm infant is retinopathy of prematurity (ROP), a condition of the retina that is severe but can be treated when detected. Despite recent advances in the treatment of ROP, there is a need to improve diagnostics and provide reliable and equal treatment. The first aim of the project is to analyse whole-populational national register data from Norway to obtain knowledge regarding variations in oucome in Norwegian health-regions, ROP incidence and risk factors. In the next step the knowledge regarding ROP in Norway will be utilized in the development of computational simulation models to forecast ROP outcome and explore risk factors given various scenarios. In this step individual and population disease trajectories of ROP will be modelled, using national ROP register data from Norway, Sweden and the Extreme-Low-for Gestational-Age-Study (ELGAN) in the USA, with the goal to provide a tool to identify individuals at risk with the highest need of specialized treatment. The originalities of this project are several. First we will for the first time analyse national whole-population data regarding ROP incidence, geographical distribution, outcome and risk factors in Norway. Secondly we will in a novel way exploit collected population register data on ROP from Norway, Sweden and USA to develop and refine a computational data model for ROP progression over time in an individual patient and in simulated populations of patients.

The field of computational disease modeling is still young and no attempts have been made as of yet to generate population models of preterm birth and associated disorders of the preterm newborn. Visiting professor to the Department of Neuromedicine and Movement Sciences, Olaf Dammann and coworkers at Tufts University in Boston have however developed a Python script that generates a database of simulated newborns and that has been able to replicate distributions of real population data. The student will be involved in the refinement of this model based on register data from Norway, Sweden and USA. Proficiency in programming languages such as Python is an advantage. 

 For more information please contact: Researcher Tora Sund Morken, Eye Department, St.Olav Hospital, email tora.s.morken@ntnu.no, phone 72 83 63 33/995 99 705

 \\Human bocavirus and other 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 bocavirus (HBoV), belonging to the parvovirus family, was detected in 2005. Genotype HBoV1 often appears simultaneously with other viruses and in healthy children, as well as in children with RTI, but still, we have docuented that HBoV1 is likely to cause RTI in children.

Aim: In this project, we aim to describe the epidemiology and clinical findings in children infected with HBoV1.

Methods: We have a dataset consisting of approximately 5000 children hospitalized with RTI and 600 controls, who were enrolled into a cohort study during an eleven yearlong period from 2006 – 2017. The presence of 17 viruses and several bacteria have been assessed, using modern nucleic-acid based methods and culture techniques. HBoV1-DNA appears in approximately 5-10% of both cases and controls, but mRNA mainly appears among those with RTI. Co-detection of one or more other viruses is common in both cases and controls. The task is, in a population based study, to describe the incidence of HBoV1 single infections (defined as a positive HBoV1-mRNA and/or high HBoV1-DNA level), among hospitalized children in Sør-Trøndelag county, describe the clinical manifestations in those with true HBoV1 infection, and explore the impact of co-detections of other viruses.

Research student thesis: The dataset may be used to write 2-3 papers. To fulfill a PhD, the student have various options, e.g. study the excretion time in HBoV1 infected children.

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.

 In the same dataset, we have also data on other viruses such as adenovirus, para-influensaviruses and rhinovirus, to be used in other research student projects.

Artificial Pancreas Trondheim (APT) #

The Artificial Pancreas Trondheim (APT) research group work on developing a Double Intraperitoneal Artificial Pancreas (DIAP) to be used by patients with diabetes mellitus type 1 (DM1). The work is founded by the regional health trust and by the Research Council of Norway.

Many groups around the world work on making an Artificial Pancreas (AP). Common to almost all of them is that they use commercially available Continuous Glucose Monitors (CGM) that measures glucose in the subcutaneous tissue, and commercially available insulin pumps delivering insulin subcutaneous. This approach struggle with major delays both in glucose sensing and the effect of subcutanoues administered insulin of the blood glucose level. The first AP based on this approach has been approved by the US Food and Drug Administration (FDA). However, this AP is not fully automated as the patients has to initiate the insulin boluses when eating. Despite this the average glucose levels is still well into the diabetic range.   

The APT group and the DIAP project aim at making an AP that shall keep the glucose levels in or close to the non-diabetic range. To achieve that we focus on a double intraperitoneal approach, i.e. we will both measure glucose and deliver insulin in the peritoneal cavity. By doing so we will have a faster glucose sensing and a much faster insulin effect on the glucose levels. We have modelled that by this approach it should be possible to keep glucose in the non-diabetic range. The major challenges are the development of the technology for intraperitoneal glucose sensing, the development of an abdominal port and making the algorithm to be included in the computer transforming measured glucose levels to insulin delivery.

The APT group is primarily based at the Department of Clinical and Molecular Medicine at the Faculty of Medicine and Health Sciences. The group include researchers from the MH Faculty as well as from the Department of Electronic Systems, the Department of Engineering Cybernetics and Department of Mechanical and Industrial Engineering at NTNU. As the group involve many different specialties, working in the group support the understanding of the emerging possibilities and importance of technology for future health care solutions, including how to develop them.

The student(s) will be included in the research group and participate in the biweekly meetings were different parts of the project is presented and discussed. Thus, working in the APT group should be particularly attractive for medical students with interest and/or insight in technology. Students will have their own sub-projects within the major project. Due to possible intellectual property rights further details can only be presented after a Non-Disclosure Agreement (NDA) has been signed.

The APT have the possibility to have 2-3 students involved. Below are indicated possible areas to be involved in. However, students with particular interest related may also evolve their own ideas if they are adjustable to the overall goals of the research group.

1.      Study possible mechanisms, i.e. hormones, involved in the acute insulin resistance seen in DM1 patients with hyperglycemia. This relates to the work on the steering algorithms that will be developed for our AP.

2.     How to increase the absorption of subcutaneous insulin? Is it possible decrease the day-to-day variation of absorption of subcutaneous insulin and thereby have a more predictable insulin effect?

3.   How to identify meals as soon as possible after a meal to be able to as safe as possible ti have an AP delivering insulin as fast as possible after meal intake.

 Kontaktperson: Professor Sven M Carlsen 

Development of novel myeloma drugs #

(New 28.06.18) This is an innovative and exciting project, with many options for an enthusiastic student. The overall goal is to develop better treatment options for patients living with multiple myeloma. The student will be part of Center for myeloma research, a large translational research group with projects ranging from pure basic research, via in vivo models, to clinical trials. We have many international collaborators, thus there are good options for research stays abroad during the project.

Myeloma is one of the most common hematological cancers, and in Norway 449 patients were diagnosed with the disease in 2016. The number of people living with myeloma in Norway increased with 55% from 2006 to 2016, partly due to an aging population and the introduction of novel therapeutic agents. The median overall survival is now 6-7 years. However, the median age at diagnosis is 69 years and an increased prevalence of myeloma in older people limits use of commonly used therapies due to poorer efficacy and co‐morbidities. Most myeloma patients develop a severe osteolytic bone disease accompanied by pain and fractures. With more people living with the disease, it is important to improve treatment, not only to cure, but also to improve the patients’ quality of life. Novel treatment strategies are therefore urgently needed. Myeloma cells are sensitive to BMP-induced apoptosis and BMPs are involved in bone formation, indicating that increasing BMP activity in the bone marrow could be used to treat myeloma patients. 

We aim to generate BMP-modulating drugs for myeloma treatment. To reach this ambitious goal, the project is divided into intermediate objectives needed to reach the overall aim.

  1. High-throughput drug screening: for drugs that potentiate or inhibit the activity of BMPs. We have already optimized the screening model for high throughput in a collaboration with SINTEF. Preliminary screening results are provided in the proposal.
  2. Validation of identified compounds. We have made and tested tools for validation, such as reporter cell lines.
  3. Mechanism of action. Approach depends on screening results. We will use established methods to screen for involved pathways.
  4. Optimization of drugs for increased efficacy and in vivo administration. We collaborate with experienced chemists at Dep. of Chemistry to optimize compounds.
  5. Testing of in vivo efficacy and biodistribution. We will use our established in vivo model for testing, including advanced analyses on bone effects.

 We also have other projects related to this one, which could be suitable for a student. 

Main supervisor is researcher Toril Holien.

Quality of life in adults born with low birth weight and associations with cognition, mental and physical health and cerebral MRI #

(New 22.6.18)
By longitudinal research in low birth weight individuals, the aim is to explore health-related quality of life in adulthood in relation to mental and physical health, cognition and cerebral MRI findings. Data are collected and ready to be analysed. The project is a collaboration between research groups at Department of Clinical and Molecular Medicine, Department of Neuromedicine and Movement Science, the MR Centre at Department of Circulation and Medical Imaging and Department of Mental Health at the Faculty of Medicine and Health Sciences in addition to Department of Psychology at the Faculty of Social and Educational Sciences. This project contains data that are unique and represents cutting edge research with potential benefits for clinicians and individuals born with low birth weight.

 Kontaktperson: karianne.i.evensen@ntnu.no

Global health #

(Updated 30.05.18)
Project title: Evaluating interventions in antenatal care to identify and assist victims of gender based violence in Nepal and Sri Lanka.

Gender-based violence is prevalent around the world and covers a range of events which pose significant risks for the physical, sexual and psychological health of women and children, in addition to their social and economic well-being (for example, human trafficking, rape, sexual abuse of children, intimate partner violence). Our study focuses on violence that occurs within families – domestic violence. The overall objective is to improve antenatal care services for victims of domestic violence in Nepal and Sri Lanka in order to reduce maternal and infant morbidity and mortality. This project was initiated by partners in Nepal and Sri Lanka and builds upon existing multi-disciplinary research collaborations. PhD students in Nepal and Sri Lanka have carried out the majority of the research activities. We are now hoping to embark on a second phase of this study. At present, we do not have a concrete project to offer, but we are interested in hearing your proposals/suggestions. We invite students in the Forskerlinjen i medisin at NTNU to contact us to discuss the possibility of a research project which could fall within the larger framework of this study.

Contacts,  Institutt for samfunnsmedisin og sykepleie:
Berit Schei, Professor
Elisabeth Darj, Professor
Jennifer Infanti, Postdoctoral researcher

Svangerskapsdiabetes #

(Nytt tilbud pr 29.05.18). I perioden 2007-2009 ble det gjennomført en stor randomisert kontrollert studie som inkluderte 855 gravide kvinner. Hensikten var å se om trening i svangerskap kan forebygge eller behandle svangerskapsrelaterte plager. Det primære utfallsmålet var svangerskapsdiabetes, men vi fant ingen forskjell i forekomst mellom trenings- og kontrollgruppen. Derimot var forekomsten høyere (6%) enn forventet i en gruppe friske, kaukasiske, gravide kvinner. Både mor og barn er fulgt opp 7 år etter fødsel. Det er samlet inn verdifull data som gir muligheter for å besvare relevante kunnskapshull innen svangerskapsdiabetes. Det er blant annet gjennomført OGTT to ganger i svangerskap og 3 mnd postpartum, målt vekt og tatt biologisk materiale til analyse og lagring. I tillegg er helsestatus kartlagt ved spørreskjema. Dataene gir muligheten til å besvare blant annet følgende forskningsspørsmål:  

-          Er det sammenheng mellom vitamin D nivå og insulinsensitiviteten i svangerskap?
-          Er det en genetisk disposisjon for svangerskapsdiabetes (basert på SNP-analyser)?
-          Hvordan er helsestatus hos mor og barn (GDM vs. non-GDM) 7 år etter fødsel?
-          Er det sammenheng mellom aktivitetsnivå før svangerskap og tidlig i svangerskap
           og insulinsensitiviteten  (basert på 4 norske cohorter, N=3000)?

Prosjektet har et folkehelseperspektiv. Svangerskapsdiabetes øker risikoen for komplikasjoner for både mor og barn under graviditet, fødsel og senere. Både mor og barn har høyere risiko for å utvikle type 2 diabetes senere i livet. Det er økende forekomst av inaktivitet, overvekt og livsstilsrelaterte lidelser i samfunnet, og svangerskapet er en svært viktig periode i utviklingen av barnets metabolske helse. Bedre kunnskap om svangerskapsdiabetes og forebygging av svangerskapsdiabetes er nødvendig.

Hovedveileder:  Forsker Signe Nilssen Stafne, Institutt for samfunnsmedisin og sykepleie

 Analinkontinens #

(Nytt tilbud pr 29.05.18)
I perioden 2007-2009 ble det gjennomført en stor randomisert kontrollert studie som inkluderte 855 gravide kvinner. Hensikten var å se om trening i svangerskap, inkludert bekkenbunnstrening, kan forebygge eller behandle svangerskapsrelaterte plager. Både mor og barn er fulgt opp 7 år etter fødsel. Analinkontinens defineres som ufrivillig lekkasje av luft og/eller avføring og rammer en stor andel av den kvinnelige befolkningen. Svangerskapet og fødsel er en av de viktigste risikofaktorene. Analinkontinens reduserer livskvaliteten betydelig. Til tross for det er det få kvinner som søker helsehjelp pga tabu og lite kunnskap om behandlingstiltak. Analinkontinens er multifaktorielt og faktorer som kost, muskelfunksjon og helsestatus er trolig medvirkende. I den aktuelle studien er det samlet inn verdifull data som gir muligheter for å besvare relevante kunnskapshull innen analinkontinens. Det er blant annet kartlagt kost på makro- og mikronivå både i svangerskapet og etter, samlet inn biologisk data og kartlagt helsestatus. Dataene gir muligheten til å besvare følgende forskningsspørsmål:

-          Er det sammenheng mellom kost og analinkontinens i svangerskap
           og opp til 7 år etter fødsel?
-          Er det sammenheng mellom vitamin D nivå i svangerskap
           og analinkontinens?
-          Er det sammenheng mellom relaxin og androgene hormoner
           og forekomst av analinkontinens?
-          Hvilke faktorer ved svangerskap og fødsel predikerer
           analinkontinens 7 år etter fødsel?

Prosjektet har et folkehelseperspektiv. Analinkontinens er hyppig forekommende og forekomsten er forventet å stige grunnet økt levealder. Kostnadene til utredning og behandling av analinkontinens er svært høye. Det er behov for mere kunnskap om hvordan analinkontinens kan forstås, forebygges og behandles. Det er også et stort behov for informasjon om tilstanden til både kvinner og helsepersonell.

Hovedveileder:  Forsker Signe Nilssen Stafne, Institutt for samfunnsmedisin og sykepleie

Circulating tumor DNA as a biomarker in multiple myeloma #

(Nytt tilbud pr 29.05.18) Prosjektet har rom for 1-2 forskerlinjestudenter. 

The myeloma research group work on different aspects regarding multiple myeloma (bone marrow cancer). The group consist of 20 researchers, post docs and PhD students, with a wide range of different backgrounds; molecular biologists, clinicians, biophysics and bioengineers. The research group has a close collaboration with the department of Hematology at St. Olav’s University Hospital. In this project, there is a close collaboration also with the Genomic Core Facility at NTNU (to perform deep sequencing), and a research group in Toronto, Canada, regarding bioinformatic analysis. Primary myeloma patient samples will be from Biobank1. 

Background of the project: Multiple myeloma (MM) is a cancer that affects the plasma cells in the bone marrow. Malignant plasma cells that proliferate usually produce monoclonal antibodies (immunoglobulin) that can be measured by protein electrophoresis. This biomarker for tumor load called M protein has for a long time been used to diagnose multiple myeloma and monitor tumor load during treatment. MM is characterized as a heterogenous disease, with many chromosomal changes and DNA mutations present in the tumor plasma cells, many of these acquired during the disease course. Although new drugs introduced the last decade has substantially improved survival in these patients, myeloma is still an incurable disease, and there is little knowledge of which patients that will respond to which treatment. In addition, drug resistance is a major problem in myeloma treatment. It is not well known how drug resistance occur, and if this is due to acquired chromosomal changes or mutations in DNA, or other factors.    

Elevated levels of cell free DNA (cfDNA) have been found in blood plasma and serum of cancer patients compared to healthy controls, and when derived from tumor cells this is called circulating tumor DNA (ctDNA). In a previous study in our group (Rustad et al., 2017, Haematologica), we were able to monitor mutations (1-3 per patient) over time using a method called digital droplet PCR. We then related the levels of mutations to tumor load and treatment response as evaluated by M protein. The results showed a marked covariation with M protein, suggesting that ctDNA can be used as a biomarker in MM. However, due to the wide heterogeneity of MM, the best method will be to follow many mutations in parallel.

In addition, there is a subgroup of myeloma patients where the use of ctDNA as a biomarker could improve monitoring of the disease; 18 % of myeloma patients are having non- and oligo-secretory disease. In these patients M protein is absent or at low levels, and M protein cannot reliably be used as a biomarker.

Project:// In this research project, we want to detect mutations in ctDNA on a larger scale, using deep sequencing of many myeloma related genes simultaneously. We will monitor MM patients before, under and after treatment by performing deep sequencing of circulating cell-free tumor DNA from blood samples. This has the potential to give us information on treatment effect, clonal dynamics of the tumor and may allow for earlier detection of (secondary) resistance mutations under therapeutic pressure. This can be important aspects for treatment decisions. In addition, this method can improve disease monitoring in a subgroup of patients with non- or oligo- secretory disease.

Methods:// The methods to be used in this project will include isolation of cell-free DNA from plasma/serum, digital droplet PCR (for verification of sequencing data), quantification of DNA samples on qubit, collection of clinical data, and also to learn and perform bioinformatic tools to analyze the sequencing data. Good computer skills will therefore be preferable for this project.  

Main supervisor: Researcher Kristine Misund Institutt for klinisk og molekylær medisin

Studying the function of brain circuits in helath and disease #

(Updated 28.05.18)
Our interdisciplinary laboratory is mixture of enthusiastic life scientist, physicists and engineers, whose goal is to understand the fundamental principles underlying the function and development of neural circuits in health and disease. In order to achieve this aim, we use genetically tractable small model organisms, zebrafish and fruitfly. We monitor, dissect and perturb the brain circuits, through a unique combination of functional imaging, optogenetics, electrophysiological recordings, molecular genetics and quantitative behavioral assays.

Objectives: in consulation with the supervisor, the successful student candidates will choose to work on one of the following research lines :

Our laboratory has 3 major research lines

Sensory computations: Our primary goal is to understand how sensory world (smell, vision and taste) is represented in animal brain and how these computations regulate different behavioral programs (e.g. fear, arousal, feeding). Moreover, we are interested in understanding how these representations are modulated by behavioral states of animals (e.g, stress, reproduction and hunger). We achieve this by focusing on those brain areas that integrate information from multiple sensory modalities and closely relate to behavior (e.g. telencephalon, habenula, brainstem). Small and accessible brain of zebrafish provides an exceptional framework for studying the neural circuit computations both locally and across multiple brain regions simultaneously.

The role of cilia in brain development and function: The cilium is a small cellular appendage projecting from the surface of most cells, like a tiny antenna. It can generate flow or play a structural, sensory or signaling role in many tissues. Hence, defects in cilia observed in ciliopathy patients affect multiple organs and result in developmental defects, heart and kidney disease, respiratory dysfunction, anosmia and neurological disorders. Using a combination of genetics and imaging techniques, we investigate cellular and physiological mechanisms regulating ciliary function and motility, in vivo. Altogether we expect our work to set a framework for studying and characterizing human ciliopathies using zebrafish as a model organism.

Neural circuit mechanisms underlying neurological diseases: Finally, our laboratory is always open to reach out to the local and international science community for providing the expertise in studying neural circuit function and architecture to investigate the changes in brain circuits underlying neurological diseases. A small core in our laboratory is interested in applying systems neuroscience tools to zebrafish and fruitfly models of neurological diseases (e.g. Fragile X syndrome and epilepsy). Our aim is to understand the alterations in neural circuit computations and connectivity in these disease models.

On the long term, we expect that our work will inspire scientist not only to simulate and imitate brain circuits in silico, but also comprehend neural mechanisms underlying neurological conditions such as stress, anxiety, eating disorders or neurodegenerative diseases and inspire the development of novel therapies.

Methods we use:
– Two-photon microscopy
– Optogenetics
– Electrophysiological recordings
– Applied Mathematics
– Molecular genetics
– Behavioral assays

  •  Enthusiastic medical students with background (or interest) in programming using MATLAB or similar environments are highly encouraged. 

Main supervisor: Emre Yaksi     Kavli Institute for Systems Neuroscience / Center for Neural Computations    www.yaksilab.com

Impact of oxidative DNA damage repair on cognitive aging    #

DNA repair is fundamental for maintaining genomic integrity in neuronal cells and thereby proper brain functions. Base excision repair (BER) is the major pathway for repair of cellular oxidative DNA damage and has been implicated to play an essential role in aging brain as well as age-related neurodegeneration. Oxidized DNA base lesions are recognized and excised by specific DNA glycosylases, initiating BER. Recent studies of several DNA glycosylase knockout mouse models (e.g. Neil1-/- Neil2-/-, Neil3-/-, Ogg1-/- Mutyh-/-) revealed an impaired cognitive phenotype by ‘Morris Water Maze’ spatial behavior task (Regnell et al., 2012; Bjørge et al., 2015), implicating a special role of DNA glycosylases in spatial learning and memory. Spatial memory, the memory for spatial configuration and the ability to navigate in an environment, is a key component of episodic memory that have been shown to decline during aging and to age-related neurodegenerative diseases. The hippocampal-entorhinal spatial network is the central hub for memory encoding and processing and is a simple yet powerful model for understanding the cortical brain functions, due to its distinct functional relevance, dedicated spatial cell types, verified spatial circuits as well as its easy experimental access comparing to other systems of the association cortices. In this project, we will focus on the hippocampal-entorhinal spatial representation system and use a multi-disciplinary approach combining neurobiological, anatomical, electrophysiological, behavioral, biochemical and molecular methods to elucidate how BER of oxidative DNA damage contributes to cortical brain functions during aging.

We aim to explore the functional relevance and neurobiological mechanisms of oxidative DNA base lesion repair in the hippocampal-entorhinal spatial representation system.

 (1)    Determine whether the observed cognitive variations in behavior tests in three different DNA glycosylase deficient mice strains (e.g. Neil1-/- Neil2-/-, Neil3-/-, Ogg1-/- Mutyh-/-) are associated with alterations in the hippocampal-entorhinal spatial representation system.
(2)    Determine the neurobiological mechanism underlying how hippocampal-entorhinal space circuit is interfered in these glycosylase deficient mice, and whether it is age-dependent.
(3)    Determine whether the role of glycosylases in cognition and behavior are associated with gene regulatory functions in the brain or with repair of oxidative DNA damage accumulated during aging. 

This is a multidisciplinary project that will use a broad range of advanced methods and technologies from multiple research disciplines, such as molecular and cellular biology, biochemistry, neurobiology, electrophysiology and animal behavior.

(1)    Immuno-histochemical staining and confocal microscopy for characterization of tissue sections
(2)    Behavior paradigms for spatial learning and memory
(3)    Neuronal recording in freely moving mice to visualize and monitor functionally specialized spatial cells, e.g. place cells in the hippocampus (HPC) and/or grid cells, head-direction cells, border cells, speed cells in the medial entorhinal cortex (MEC)

 Contact persons: Forsker Jing Ye (main supervisor), jing.ye@ntnu.no or Professor Magnar Bjørås, magnar.bjoras@ntnu.no, Department of Cancer Research and Molecular Medicine

Impact of PARylation on cognition and neurodegeneration #

 Poly(ADP-ribosyl)ation (PARylation) is catalysed by Poly(ADP-ribose) polymerases (PARPs). PARP3 is structurally related to the well-studied PARP1 and PARP2, however, the functions of PARP3 remain largely unknown. Recently, several reports have demonstrated a specific role of PARP3 in cellular responses to double strand breaks in genomic DNA, implicating that PARP3 functions as a central mediator that coordinates the immediate detection and repair of DNA damage. Although PARP3 has been identified in all the brain regions and genetic variants of human PARP3 are associated with neurodevelopmental disorders, there are no experimental support so far about the impact of PARP3 on brain function. In this project, we will investigate the role of PARP3 on physiological and pathological development in the brain. We will use a PARP3-deficient mouse model subjected to hypoxia-ischemia to study the role of PARP3 in neuroprotection and neurodevelopment. Additionally, we will use the hippocampal-entorhinal spatial representation system as a model system to study the role of PARP3 in cortical brain functions. We will also analyse brain tissue from patients diagnosed with neurodegenerative diseases to address the impact of PARP3 and PARylation in the diseased human brain. We expect that new mechanistic insight about PARP3 function in brain could lead to the development of new prognostic biomarkers and new treatment modalities that benefit patients suffering from neurodevelopmental disorders.

The primary objective of the project is to unravel new knowledge about the impact of PARP3 on neuroprotection, neurogenesis and neurodevelopment as well as on physiological and pathological development in the brain, and to understand the impact of PARP3 on cognition and neurodegenerative disease.

(1)    Determine the impact of PARP3 on cortical brain functions
(2)    Determine the role of PARP3 on neurodevelopment and memory improvement after neonatal hypoxia ischemia
(3)    Determine the impact of PARP3 deficiency on human neurodegenerative diseases 

This is a multidisciplinary project that will use transgenic mouse models, experimental disease models and a broad range of advanced methods and technologies from multiple research disciplines, such as pathology, molecular and cellular biology, neurobiology, electrophysiology as well as animal behavior.

(1)    Immuno-histochemical staining and confocal microscopy for characterization of tissue sections
(2)    Neuronal recording in freely moving mice and behavior paradigms for cognitive studies
(3)    Hypoxic-ischemia brain injury (stroke model) for neuroprotection, neurogenesis and neurodevelopment tests

Contact persons: Forsker Jing Ye (main supervisor), jing.ye@ntnu.no or Professor Magnar Bjørås, magnar.bjoras@ntnu.no, Department of clinical and molecular medicine

Tackling drug resistance in multiple myeloma #

We are looking for enthusiastic and curious students. Our vision is to characterize basic cell biological mechanisms that have a clear translational application.

 Multiple myeloma (myeloma in short) is a fatal cancer with a median survival of 5-7 years from time of diagnosis. It results from the malignant transformation and clonal expansion of antibody-producing plasma cells. It is the second most common form of hematological cancers in Western countries. Novel treatment strategies are needed to tackle treatment resistance, postpone remission, prolong survival and ultimately treat myeloma patients.   The student will study drug resistance and development through two projects.

1. De-masking myeloma cells for immune recognition.
Myeloma cells can evade immune recognition through de-regulation of cytokine loops. The task of the student is to determine how myeloma cells and macrophages can be pharmaceutically targeted to break this evasion, and thus enable the immune system to repress cancer cell expansion. This can open up to novel immune therapies for myeloma treatment.

 2. Tackling drug resistance in novel myeloma therapies.
Proteasomal inhibitors have made a big impact on myeloma treatment as they selectively kill myeloma cells. However, not all patients respond to treatment. We recently showed that clinically established drugs induce very different resistance mechanisms. In this project the student will determine whether this also is the case for the 2nd generation proteasome inhibitor ixazomib. Results of this study can indicate which patients will benefit from ixazomib-treatment, and thus help in developing tailored treatment regimes.

 Main supervisor and contact:  Kristian K. Starheim, Researcher. Co-supervisor: Geir Bjørkøy, Professor. Both at Cemir Center for Molecular Inflammation Research.

Fremtidens Operasjonsrom #

(oppdatert 06.06.18)Forskningsinfrastrukturen Fremtidens Operasjonsrom (FOR), en enhet i Forskningsavdelingen ved St. Olavs hospital, som legger til rette for forskning og utvikling innom de kirurgiske fagområdene, med vekt på minimal invasiv bildestyrt pasientbehandling og medisinsk teknologi. FOR`s infrastruktur med de 6 operasjonsstuene (FOR stuer) ved St. Olavs hospital innenfor fagområder som øre‐nese‐hals, kjeve, ortopedi, gynekologi og nevrokirurgi, i tillegg til endovaskulær og laparoskopisk behandling. Disse operasjonsrommene er utstyrt med tanke på minimal invasiv bildestyrt pasientbehandling. Det pågår også forskning og utvikling innenfor områder som arbeidsflyt, kommunikasjon og visualisering med høykvalitetsbilder.
Operasjonsstuene og forskningsverktøy som er tilgjengelig i FOR infrastruktur er i praksis moderne forskningslaboratorier. Her ligger alt til rette for at prototyper og nye behandlingsmetoder kan utvikles og testes i trygge og kontrollerte omgivelser. Her kan du leser mer om FOR - https://stolav.no/fag-og-forskning/kompetansetjenester-og-sentre/for

NorMIT- Norwegian center for Minimally invasive image guided Therapy and Medical Technologies – er et samarbeid mellom FOR og Intervensjonssenteret ved Oslo universitetssykehus (OUS). Denne nasjonale infrastrukturen skal bidra til økt klinisk og teknologisk forskning med hovedfokus minimal invasiv behandling, medisinsk teknologi, utvikling av navigasjonsteknologi og bildeveiledet behandling. Mer om NorMIT - http://normit.no/

FOR infrastruktur er tilrettelagt for og gjenspeiler det tette samarbeidet mellom klinikere, teknologer, forskere og industri. Gjennom Fagrådet i FOR sikres kvaliteten på den kliniske forskningen som foregår ved og i samarbeid med FOR.

Vi er svært interessert i samarbeid med Forskerlinjestudenter – og vi ber om at interesserte studenter kontakter oss ca. 1 år før søknad om opptak. Dette på grunn av at vi trenger tid på å forberede kliniske miljø samt veilederkompetanse slik at vi på best mulig måte kan ivareta den enkelte forskerlinjestudent.
Oppfordrer herved at innovative og motiverte medisin studenter kontakter Fremtidens Operasjonsrom – mulighetenes arena innenfor forskning og utvikling av medisinsk teknologi.

Velkommen til å ta kontakt - Vi ser frem til å høre fra dere!

Kontaktpersoner: 
Rådgiver FoU, Marianne Haugvold, marianne.haugvold@stolav.no
Avdelingssjef, Jan Gunnar Skogås, jan.gunnar.skogas@stolav.no

Hunt Longitudinal Ankylosing spondylitis and Rheumatoid arthritis Study - HuLARS #

Vi har rom for å ta inn en forskerlinjestudent fra høsten 2017. 

Revmatoid artritt (RA – leddgikt) og ankyloserende spondylitt (AS – Bekhterevs sykdom) er to vanlige autoimmune inflammatoriske leddsykdommer, som til sammen rammer 0.8-1.8 % av befolkningen. Pasientene får leddbetennelse uten å ha noen infeksjon; isteden er det immunsystemet som aktiveres i leddene via mekanismer som ikke er godt forstått. En rekke studier har vist økt mortalitetsrate ved inflammatoriske leddsykdommer. Hovedårsaken er økt risiko for hjerte- og karsykdom. Pasientene har både en uheldig profil for klassiske risikofaktorer som hypertensjon og røyking, og økt aterosklerose som følge av at grunnsykdommen gir inflammasjon. HuLARS-gruppen har et stort og mangefasettert materiale om inflammatorisk artritt i HUNT. Vi forsker også på denne pasientgruppen ved Revmatologisk avdeling ved St Olavs Hospital. Fra HUNT2 og HUNT3 har vi tilgang til data fra artrittpasienter og ca. 70 000 kontroller: blodprøvesvar, klassiske risikofaktorer for hjerte- og karsykdom, og genotypedata for undersøkelse av genetisk predisposisjon for artrittsykdom og hjerte- og karsykdom. Viktige kardiovaskulære endepunkter er tilgjengelige etter kobling til Dødsårsaksregisteret og Hjerteinfarktregisteret i Midt-Norge. HuLARS har også et delprosjekt i HUNT4, hvor datainnsamlingen starter høsten 2017. Gruppen arbeider med ulike problemstillinger som spenner over et vidt felt fra genetiske undersøkelser ved artritt til kartlegging av motivasjon for fysisk aktivitet hos artrittpasienter. HuLARS-gruppen er tverrfaglig med kompetanse innen immunologi, revmatologi, hjertemedisin, treningsfysiologi, genetisk epidemiologi og statistikk, og har også utenlandske samarbeidspartnere. Nå har vi plass til en ny forskerlinjestudent i prosjektet. 

Kontaktperson: Vibeke Videm, Institutt for klinisk og molekylær medisin

Forekomst av motonevronsykdommer i Midt-Norge #

Motonevronsykdommer er ulike nevrodegenerative tilstander som rammer de motoriske nervronene. En ikke ubetydelig andel av pasientene får også kognitive endringer, og en del får frontotemporallappsdegenerasjon. Amyotrofisk lateralsklerose (ALS) er den hyppigst forekommende motornevronsykdom med degenerasjon av både øvre og nedre motonevron som kjennetegn. Ingen kurativ behandling er tilgjengelig. Det foreligger kun sykdomsmodifiserende behandling med beskjeden effekt, i tillegg til palliativ tilnærming.

Det foregår nå en økende forskning på tilstanden, og nevrologisk avdeling ønsker nå å invitere til å søke forskerlinjestilling innen dette fagfeltet. 

Det vil være mulighet for en rekke forskjellige prosjekter, men det er tenkt at arbeidet i første omgang retter seg mot epidemiologiske studier. Det kan bli aktuelt med en rolle i rekrutteringen av pasienter til forskning. Ta gjerne kontakt for en uforpliktende prat.

Kontaktperson: Tore Wergeland Meisingset, Nevrologisk avdeling, St. Olavs Hospital.

Physical Activity, Vitamin D and Bone Health #

(Updated 29.05.2018)
Osteoporosis and fracture become increasing public health concerns and have a huge economic impact worldwide with life expectancy of people reaching a historic acme. Physical activity may postpone age-related bone loss and thereby reduce risk of fracture. Vitamin D is also suggested to play an important role in bone health. Vitamin D deficiency has been associated with bone loss and reduced muscle strength; it may also increase the risk of fracture. Previous research focused either in early growth period or in senior age. There is lack of longitudinal studies to investigate these relationships in adult population covering an entire age span.
The overall study aim of this project is to evaluate physical activity, change in physical activity and body vitamin D status in relation to longitudinal changes in bone mineral density (BMD) and fracture risk and the possible interrelationship of physical activity and vitamin D on bone health.
Data from The Nord-Trøndelag Health Study (HUNT) will be used. Physical activity and change in physical activity will be generated from HUNT1 and HUNT2 questionnaires. Serum vitamin D metabolite levels were measured in a random sample of HUNT2 population. Measurements of BMD were carried out in 1995-97 (HUNT2), 2001 and 2006-08 (HUNT3). The HUNT population data will be linked to a fracture register to ascertain information on fractures.Genetic variants will be used to investigate potential causal association between vitamin D and fracture risk, applying the Mendelian randomization approach

Main supervisor: Xiao-Mei Mai, professor, Institutt for samfunnsmedisin og sykepleie 

KOLS – hva predikerer helsestatus og behandlingsbehov? #

Helseundersøkelsen i Nord-Trøndelag har samlet data fra Nord-Trøndelag fylkes befolkning gjennom HUNT1 (1984-86), HUNT2 (1995-97) og HUNT3 (2006-08).  I alt deltok henholdsvis 75000, 65000 og 51000 personer, disse har besvart spørreskjema og deltatt i ulike målinger. Lungeprosjektet i HUNT innkalte tilfeldig utvalg av deltagere samt de som rapporterte obstruktiv lungesykdom eller symptomer på dette, til spirometri, intervju og beinmassemåling i HUNT2 og HUNT3. Ca. 11.000 personer deltok i hver av disse tilleggsundersøkelsene. Det er identifisert en kohort av personer med sannsynlig kols og blant de 2500 som fortsatt var i live i 2015, har 2100 personer besvart spørreskjema om legediagnose, kroniske sykdommer, symptomer, helsestatus, forverrelser og bruk av helsetjenester (datainnsamling avsluttet juni 2015).

Datagrunnlaget gir mulighet for oppfølgingsstudie som kan besvare blant annet følgende forskningsspørsmål:

  • Faktorer som bidrar til tidlig død
  • Faktorer som påvirker helsestatus henholdsvis 10 og 20 år etter baseline
  • Faktorer som påvirker bruk av helsetjenester henholdsvis 10 og 20 år etter baseline.

Lungeprosjektet har samlet inn store datamengder og kan tilby forskning innen mange lunge- og osteoporoserelaterte tema, alt etter kandidaters ønsker. I tillegg planlegges omfattende lungeprosjekt i HUNT4 med potensial for spennende forskningsprosjekter.
Arbeidssted: Helst HUNT forskningssenter, Levanger. Glimrende mulighet for kandidater fra nordfylket. Urbane mennesker kan også ha godt av et ruralt opphold.

Hovedveileder: Arnulf Langhammer, professor. HUNT Forskningssenter

EBBA-II studien (Energy Balance and Breast Cancer Aspects) #

En norsk randomisert klinisk intervensjonsstudie med fysisk aktivitet.
EBBA-II studien er en nasjonal brystkreft studie basert på samarbeid mellom Oslo Universitetssykehus, Drammen sykehus og St. Olavs Hospital. Studien er inkludert i norsk brystkreft gruppe, NBCG. Vi samarbeider tett med nasjonale og internasjonale forskere der vi ønsker å studere effekten av fysisk aktivitet i en intervensjonsstudie. Kvinner i alderen 18-75 år med nylig histologisk verifisert invasiv brystkreft vil kunne inngå i studien. Per november 2015 har vi inkludert nærmere halvparten av pasientene vi trenger til studien. Intervensjonsgruppen får et tilpasset fysisk aktivitetsopplegg i 12 måneder. Den består av utendørs aktivitetsøkter, ledet av fysioterapeut, samt tilpasset egen aktivitet. Kontrollgruppen kan være så mye fysisk aktiv de vil, men mottar kun standard oppfølging i henhold til NBCG sine retningslinjer. Pasientene inkluderes på diagnosetidspunktet med polikliniske kontroller etter inklusjon, 6 måneder, 1 år, 2 år, 5år og 10 år.

Mål: Forstå hvordan ulike livsstiler uttrykt av forskjeller i energiinntak, energiforbruk og kroppssammensetning påvirker utviklingen av brystkreft. Dette er ikke godt nok dokumentert pr i dag. Det er også mangel på kunnskap om mulige biologiske mekanismer relatert til dette problemet.

Dette er grunnlaget for EBBA-II-studien der vi ønsker å studere:

  • Hvilken effekt fysisk aktivitet har på metabolsk profil (kroppsmasse, lipidprofil, glukose, insulin) blant ny-diagnostiserte brystkreftpasienter under og etter brystkreftbehandling.
  • Hvilken effekt fysisk aktivitet har på tilbakefall og brystkreftprognose.

I tillegg ønsker vi å:

  • Studere endringer i kostholdet og analysere utvalgte ernæringsmarkører i løpet av intervensjonsperioden.
  • Relatere kostinntak og nivå av ernæringsmarkører til metabolske profiler (eks overvekt, lipidmønster) hos brystkreftpasienter
  • Evaluere effekt av en fysisk aktivitetsintervensjon i forhold til helserelatert livskvalitet og fysisk funksjon

Vi ønsker å integrere kandidaten i forskergruppen vår der vi har et trivelig miljø med godt samarbeid og regelmessige møter. Vi er tverrfaglig sammensatt med både leger (spesialister i onkologi, kirurgi, fysikalsk medisin og rehabilitering og psykiatri), fysioterapeuter, radiograf, sykepleier og forskere innenfor feltet idrettsfysiologi. Kandidaten må være motivert og positiv, kunne arbeide selvstendig og ta ansvar. Det ligger til rette for å finne problemstillinger av interesse i en stor mengde data som samles inn. 

Om du har interesse for forskning innenfor feltene brystkreft, fysisk aktivitet, livsstil og kreftrehabilitering, så må du gjerne ta kontakt så kan vi sammen finne frem til et prosjekt for deg.

Kontaktperson: Overlege Gro F. Bertheussen, Klinikk for fysikalsk medisin og rehabilitering, St. Olavs Hospital/Institutt for nevromedisin og bevegelse, NTNU.

Virus infection and corticosteroid treatments in asthma and chronic obstructive pulmonary disease #

Prosjektet har rom for 1-2 forskerlinjestudenter.

The “Virus infection and disease” research group work on immunological aspects of virally mediated disease and are associated with the Childhood Airway Infections Research (CAIR)-group. The group consists of clinicians and researchers within immunology, pediatrics and clinical microbiology (St. Olav’s University Hospital and Dep. of Laboratory Medicine, Children‘s and Women‘s Health). We collaborate closely with the ear-nose-throat department St.Olavs University Hospital to study biopsies and pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma. Our approach is to perform translational research on virus-mediated respiratory tract infections in acute and chronic disease, combining basic research, biobanks/cohorts and clinical data.

Background of the project: Chronic respiratory diseases result from abnormal immune responses to environmental agents, e.g. allergens, viruses or cigarette smoke. Exacerbations (“forverring”) of asthma and chronic obstructive pulmonary disease (COPD) cause impaired quality of life, accelerated loss of lung function, and represent a major cause of health care costs. Respiratory viral infections are the main cause of exacerbations of asthma and COPD. Consequently, it is important to study viral-host interactions for understanding abnormal innate immune responses that occur in the context of allergens and environmental pollution. Despite therapeutic advances, treating these diseases remains a challenge. Inhaled corticosteroids are commonly used in the treatment of asthma and chronic obstructive pulmonary disease, but their effects on antiviral responses and viral loads are poorly characterised.

The purpose of the project is to assess effects of corticosteroid treatment on inflammatory markers in cellular models and compare these results to findings from patients with COPD or asthma. We will test the hypothesis that corticosteroid treatment will reduce virus-induced airways inflammation but may impair anti-viral immune responses, leading to delayed viral clearance. This will help us to understand the role of innate immune components in chronic airway inflammation and to possibly describe a novel and effective treatment approach for acute exacerbations of asthma and COPD. Current research in this field is limited and consequently this work is important to identify new therapeutic strategies and drugs.

A variety of methods relevant for clinical diagnostics, basal research and patient-specific treatments may be applied, depending on the interest of the student:

  • Molecular biology (qPCR, gene silencing), immunohistochemistry of inflamed airway tissue, advanced imaging/microscopic techniques
  • Viral propagation and characterization of viral cultures
  • Isolation and cultivation of primary human cells such as airway epithelial cells and monocytes/macrophages/dendritic cells
  • Viral infection models of cells from normal or patient-specific cells to determine the effect of anti-inflammatory agents

Contact:  Professor Marit W. Anthonsen or post. doc. Jostein Malmo.Institutt for klinisk og molekylær medisin

Brystkreft #

Brystkreft er den vanligste kreftform blant kvinner på verdensbasis med 1,7 millioner nye tilfeller i 2012. I Norge er brystkreft den vanligst kreftform blant kvinner mellom 25 og 69 år og i 2013 ble 3220 nye tilfeller registrert.

Femårsoverlevelse for brystkreft har økt fra 67,9 % i 1965 til nær 90 % i 2013. Likevel døde 630 kvinner av brystkreft i 2013.

Histopatologisk undersøkelse av svulstene danner grunnlaget for valg av behandling. Svulstene blir klassifisert i typer og histopatologisk grad i henhold til deres utseende ved mikroskopisk undersøkelse. I tillegg blir de undersøkt ved hjelp av ulike molekylærpatologiske metoder for å kartlegge biomarkører som gir informasjon om prognose og mulige behandlingsstrategier.
Breast Cancer Subtypes forskningsgruppen vil gjerne finne ut mer om de ulike svulstene. Hvorfor og hvordan ble svulsten til? Hva karakteriserer en svulst med svær dårlig prognose? Hva karakteriserer svulsten med en svært god prognose?

Gruppen har to hoved søyler: patologi og epidemiologi. Vi bruker data fra store befolkningsundersøkelser kombinert med molekylærpatologiske undesøkelser av vev fra brystkreft til å finne ut mer om disse spørsmål.

Dersom du liker å løse gåter, er nysgjerrig på hva som skjer i celler og vev ved kreft og ønsker å være en del av en tverrfaglig gruppe som forsker på dette, ta gjerne kontakt med professor Anna Bofin. Institutt for klinisk og molekylær medisin

The role of motile cilia in sensory coding and neurological diseases   #

- Project in Neuroscience at CNC/Kavli Institute for System Neuroscience.  1 student wanted.

Background of the lab: The main goal of Yaksi laboratory is to understand the fundamental principles underlying the function and development of neural circuits in a small and genetically tractable model organism, the zebrafish. In order to accomplish this goal we exploit chemosensory systems. We develop and use novel technologies and analytical methods to monitor, dissect and perturb the neural circuits of developing and adult zebrafish brain. The Yaksi laboratory is also interested in applying systems neuroscience tools to zebrafish and fruit fly models of neurological diseases (e.g. Fragile X, epilepsy, ciliopathies). Our aim is to understand the alterations in neural circuit computations and connectivity in these disease models, in order to inspire the development of novel therapies. For more details and contact please visit www.yaksilab.com  and The Yaksi Group at Kavli.

Background of the project: Cilia, which may be motile or immotile, are microtubule projections emanating from most cells of the body. Motile cilia, which are important for generating flow or motion are present on many epithelia. In the respiratory tract for instance, motile cilia generate a mucus flow which prevents clogging of the tracts and infection. Previous work has also shown that airway cilia can sense and respond to toxins and noxious compounds by changing their beating frequency thereby protecting the lungs. Whereas the immotile cilium known as the primary cilium functions mostly as a sensory organelle during cell signalling. The importance of cilia in health is emphasized by a class of syndromes grouped under the term ciliopathies which manifest with a wide variety of symptoms e.g. respiratory dysfunction, anosmia, developmental defects, mental retardation, infertility, etc.

Objectives: The objective of this project is to analyse the structure and function of motile cilia in the olfactory epithelium of the zebrafish. Our main goal is to establish this model as a high throughput approach for studying human ciliopathies. Specifically, this project will focus on:

  • Understanding and characterizing the homologies between the motile cilia on zebrafish olfactory epithelium and the mammalian respiratory epithelium.
  • Investigating the interplay between ciliary beating and chemosensory computations. Specifically we will study whether the ciliary beating frequency can be regulated by odors or other chemical cues (e.g. noxious substances) and whether the ciliary beating can modulate the olfactory perception.
  • Studying the cellular and physiological mechanisms underlying these interactions.

This work will set a framework for studying and characterizing ciliopathies in zebrafish, which is a small vertebrate that is amenable for high throughput in vivo drug screens.

Methods: 

  • Molecular biology and Immunohistochemistry/Histology
  • Behavioural assays
  • Functional imaging (e.g. high speed microscopy and two-photon microscopy),
  • Optogenetics
  • Image processing
  • Molecular genetics

Main supervisor: Nathalie Jurisch-Yaksi in www.yaksilab.com

Beskytter osteoporose mot kreft? #

Dette er et epidemiologisk forskningsprosjekt og det forutsetter interesse for statistiske analysemetoder og evne til systematisk å arbeide med store datamengder. Det vil være nødvendig å lære om hormonenes effekt på vev og organismer og å være nysgjerrig på hvilke faktorer som kan virke inn på dette samspillet. Ved å fordype seg i dette arbeidet vil en interessert kandidat lære mye om epidemiologi, samfunnsmedisin, folkehelse og befolkningsundersøkelser generelt.

Flere kreftformer er hormonavhengige. Dette gjelder bl.a. kreft i bryst, livmor, tykktarm, prostata m.fl. Teoretisk kan man tenke seg at lav bentetthet, raskt bentap og osteoporotiske brudd  kan være en indikator på lav østrogenpåvirkning og at dette igjen kan beskytte for utvikling av hormonavhengige kreftformer. Bentetthet er målt i helseundersøkelsene i Nord-Trøndelag og i Tromsø der nesten 28000 kvinner og menn er målt minst én gang, og ca. 11000 av disse målt to ganger etter et intervall på 5-7 år. Det er også samlet inn mye data om hvem som opplever osteoporotiske brudd. Materialet er koblet til Kreftregisteret for å identifisere krefttilfellene.  Formålet med studien er å se om det er en sammenheng mellom bentetthet og bentap og total kreftforekomst og om dette gjelder bestemte kreftformer. Materialet skal også kobles  til Dødsårsaksregisteret for å studere  sammenhengen mellom bentetthet, bentap og overlevelse av kreftsykdom. Studien vil være et bidrag til større forståelse av kjønnshormoners betydning i helse og sykdomsutvikling, men også om hva som påvirker variasjon i dette.

Kontaktperson er professor Siri Forsmo, Institutt for samfunnsmedisin og sykepleie

Correlative microscopy, combining confocal, multifoton imaging and electron microscopic analysis at the nanoscale #

Traditional electron microscopic techniques, immunolabeling with pre- and post-embedding use of epon and lowicryl resins, need to be extended with large scale ultrastructural microscopy. Modern application of computerized scanning transmission electron microscopy allows acquiring datasets in an automated way that permits analysis of large numbers of spines and synapses. This is of great advantage in electron microscopy since high resolution images can be compared over large surface areas and allows studying details that up till now were easily overlooked.

To read a description of this project, download this pdf-document.

Kontaktperson: Professor Johannes Van der Want.Institutt for klinisk og molekylær medisin

Prognostiske faktorer i hjernesvulster #

(Oppdatert 28.05.18)
Prosjektet «Prognostiske faktorer i hjernesvulster» har pågått i mange år, og  har flere samarbeidspartnere på St. Olav og på NTNU.  På St. Olav er det tett samarbeid med Avdeling for patologi, nevrokirurgen og kreftavdelingen, på NTNU med Institutt for nevromedisin og Institutt for sirkulasjon og bildediagnostikk. For tiden er det tre forskerlinjestudenter og en LIS-lege som arbeider med prosjekter innen hjernesvulster av typen astrocytomer og meningeomer. Prosjektene går i korthet ut på å identifisere markører i vevssnitt som kan gi verdifull informasjon  og hjelp i diagnostisk, prognostisk og terapeutisk øyemed.  Nye aktuelle prosjekter er tilgjengelige med forsking på disse svulstene.  Det foreligger allerede godt registrerte pasientdata, og problemsstillingene er veldefinerte og interessante.  Det fokuseres på grundig opplæring og veiledning og god struktur i arbeidet.  Vedkommende som søker, må være glad i å se mikroskop og i å gjøre praktisk arbeid på histologilaben.   Kandidaten må være motivert og positiv, kunne arbeide selvstendig og ta ansvar.  Det er et trivelig miljø i gruppen med godt samarbeid, og resultatene har vært gode der allerede tre forskerlinjestudenter avsluttet sine prosjekter med doktorgrad.

Kontaktperson: Professor Sverre Helge Torp.Institutt for klinisk og molekylær medisin

Forskning på cerebral parese #

Den største og mest aktive forskningen innen barnemedisin ved NTNU, dreier seg om perinatal hjerneskade - det vil si hjerneskader som man får i mors liv, eller like etter fødselen.

I denne gruppen forsker vi  på flere tema, blant annet cerebral parese (CP), som er en viktig følge av slike skader. CP som er den hyppigste nevrologiske diagnosen hos barn, er en samlediagnose som er karakterisert ved at barna har vansker med motorikk og balanse, men også med andre funksjoner, som kognitiv funksjon, språk, hørsel og syn, og de kan ha epilepsi. Cirka to av 1000 nyfødte barn får CP. Vi forsker på forskjellige sider av CP. Vi er blant annet opptatt av etiologi, diagnostikk og behandling.
Gruppen vår er tverrfaglig sammensatt, av leger, fysioterapeuter, ergoterapeuter og psykologer. Vi har også flere forskerlinjestudenter og hovedoppgavestudenter.

Om du har interesse for å forske på barn, - og kanskje tenker på å bli barnelege, og eventuelt også er interessert i å hjelpe funksjonshemmede, så må du gjerne ta kontakt med meg, professor Torstein Vik, så kan vi sammen finne frem til et prosjekt for deg, avhengig av om du er interessert i klinisk forskning eller mer epidemiologisk forskning.

Her finner du kontaktinformasjon, og litt mer om forskningen.
Her kan du se film der forskerlinjestudent Kristin Melheim Strand forklarer hva Cerebral Palese er, og forteller om sin forskning på sammenheng mellom Cerebral Palese og svangerskapsforgiftning.

Helsetjenesteforskning   #

Beskrivelse av pasienters forløp gjennom helsetjenesten I et pågående forskningsprosjekt er det gitt tillatelse til å hente inn data om kontakter over to år som mange tusen  pasienter har hatt med ulike helsetjenester; sykehus, pleie og omsorg, fastleger, legevakt, rehabilitering, spesialister mm. I tillegg skal pasientenes vurdering av det forløpet de har vært igjennom hentes inn.

Dette gir muligheter for mange ulike oppgaver, fra å se på forløpet til utvalgte grupper av pasienter (alder, diagnoser mm) til hva som predikerer bruk av bestemte helsetjenester.

Oppgaven passer for studenter med interesse for samhandling i helsetjenesten og hvordan dette oppleves fra pasientenes perspektiv. Det foreligger en protokoll som kan brukes for å lage en egen protokoll for oppgaven.

Kontakt: Professor Aslak Steinsbekk, Institutt for samfunnsmedisin og sykepleie 

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For å få vite mer om forskerlinjestudiet og hvordan finne prosjekt/veileder, ta kontakt med faglig leder for forskerlinjen, professor Anna Bofin, eller studiekonsulent May Karin Dyrendahl. #

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

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