Resolution of inflammation – the role of natural killer cells Supervisor: Jóna Freysdóttir (jonaf@landspitali.is) and Ingibjörg Harðardóttir (ih@hi.is) Professors at the Faculty of Medicine About the project: Resolution of inflammation is neccessary to prevent the inflammation from becoming chronic. Chronic inflammation is involved in many disease pathologies, including that of coronary heart diseases, cancer and Alzheimer‘s. Natural killer cells are indisposible for timely resolutio of inflammation. Natual killer cells will be isolated from blood and the effects of various mediators/molecules on their capacity to induce resolution of inflammation studied. The regulation of vascular tone and wall tension in arteries Supervisor: Þór Eysteinsson (thoreys@hi.is) Professor at the Faculty of Medicine of the University of Iceland About the project: We are searching for a motivated person with a background in the biomedical sciences to work on a 90 ECTS MSc project, to study the regulation of vascular tone and wall tension in arteries (pig retinal arteries and mouse mesenteric arteries), using segments of these vessels in a small wire myography preparation, and fundus imaging and fluorescent angiography from rodent eyes, in anesthetized animals. In addition, molecular methods to localize relevant proteins on vessels and the levels of expression of these proteins will be used. The candidate needs to have basic knowledge of cell physiology, and smooth muscle function. The project is supervised by Þór Eysteinsson and Andrea García-Llorca in the Department of Physiology. The role of microphthalmia-associated transcription factor (Mitf) gene in human choroidal neovascularization disease Supervisor: Þór Eysteinsson (thoreys@hi.is) Professor at the Faculty of Medicine of the University of Iceland About the Project: Choroidal neovascularization (CNV) is one of the leading causes of vision loss in the elderly population and occurs in many macular ocular diseases like age related macular degeneration (AMD). Microphthalmia-associated transcription factor (Mitf) plays a crucial role in cellular functions and development of the retinal pigment epithelium (RPE) and could play a critical role in development of CNV. The project will provide better knowledge about parameters influencing inducement and regulation of CNV pathology by the Mitf gene and possible treatments methods for CNV. The experimental mouse model of laser-induced CNV will be used to study the progression of the disease. CNV will be induced on both eyes by laser photocoagulation in Mitf mutant and wild type mice. The role of Rhox transcription factors on mouse primordial germ cell specification Supervisor: Erna Magnúsdóttir (erna@hi.is) Associate Professor at the Faculty of Medicine of the University of Iceland About the project: The Rhox family transcription factors consists of 33 homeobox factors that are encoded by genes on a single cluster on the X-chromosome in the mouse. Opposite to the related conserved Hox gene family, Rhox genes are rapidly evolving. Very little is known about the function of these factors, what genes they regulate and what proteins they interact with, but they are thought to have evolved to repress transposons in the germ-line during epigenetic reprogramming. There are various options for MS projects on the Rhox factors, working on interacting partners or gene expression control in stem cells and primordial germ cells using mouse embryonic stem cell culture models. The student would learn to perform Western Blotting, immunofluorescence microscopy, real time PCR as well as cell culture of mouse embryonic stem cells, and the project would be developed based on the student‘s interest. Transcriptional and epigenetic regulation in lymphoma Supervisor: Erna Magnúsdóttir (erna@hi.is) Associate Professor at the Faculty of Medicine of the University of Iceland About the project: Waldenström macroglobulinaemia is a rare incurable lymphoma that is caracterized by bone marrow infiltrate of B-lymphocytes that secrete high levels of monoclonal IgM. The disease is interesting as it is related to myeloma and B-cell lymphomas and has certain characteristics of both diseases, but is less aggressive. We are interested in knowing how transcription factors might control tumour initiation and progression, but very little is known about how epigenetics and transcriptional control affect the disiease, and to which extent these are related to that of myeloma or lymphoma. There are multiple different projects possible, depending on the studen‘ts interest. The student would for example learn western blotting, immunofluorescence and confocal microscopy, cell culture, real time PCR in addition to more specialized methods related to transcriptional control. We would develop the project with the student‘s interest in mind. Effects of statins on mitochondrial biogenesis and mitophagy Supervisor: Francois Singh (francois@hi.is) Assistant Professor at the Faculty of Medicine of the University of Iceland Statins are amongst the most prescribed medications globally and are unquestionably the most effective drugs for the prevention and treatment of CVD associated with dyslipidemia, but their use is increasingly associated with a wide spectrum of skeletal muscle and metabolic dysfunction. In addition to inhibition of HMG-CoA reductase, statins inhibit mitochondrial respiratory chain complexes I and III and promote cytotoxic levels of damaging reactive oxygen species (ROS) in glycolytic skeletal muscles. However, low dose statin prophylaxis is associated with beneficial effects of ROS-dependent pathways and mitochondrial hormesis in oxidative skeletal muscles. Muscle phenotype and mitochondrial content appears to underpin statin tolerance. The role of statins on mitophagy, is however still poorly understood. Our aim is first to define the mechanistic basis of how statins alter mitochondrial homeostasis by altering the balance between mitophagy and mitochondrial biogenesis in mammalian systems. Subsequently, we intend to enhance statin tolerance in cells by modulating mitochondrial homeostasis pharmacologically and genetically. Multivariate analysis of cell-free DNA from BRCA2-999del5 carriers Supervisor: Berglind Ósk Einarsdóttir (boe@hi.is) Associate Professor at the Faculty of Medicine of the University of Iceland BRCA2 is an important protein taking part in DNA repair. BRCA2-999del5 carriers carry a 5 base pair deletion on one allele of the BRCA2 gene, which results in the protein only being expressed from one allele. The effect this has on the structure of cell-free DNA is not known. Cell-free DNA (cfDNA) is present in biofluids for example in the blood. and originates from dying cells that release their DNA into the environment. Measurements of cfDNA have a clinical value, e.g. in early detection of tumour growth and treatment monitoring. Therefore, it is important to characterize the cfDNA of BRCA2-999del5I carriers, as a baseline for future cfDNA measurements. Therefore, this project aims to perform a multivariate analysis of cfDNA from BRCA2-999del5 carriers. In this project, blood will be collected from BRCA2-999del5 carriers and a control group and the cfDNA will be isolated. A multivariate analysis of the DNA will be performed, where size, quantity, methylation pattern, and DNA damage will be measured using approved methods. The student will process blood samples, perform all measurements, collect data, and present the results to the scientific community and the public. The student will work under Berglind’s supervision but will also be part of a collaborative liquid biopsy group, which is a collaboration between experts at the faculty of medicine at the University of Iceland and at Landspítali. The role of the lncRNA FGD5-AS1 in osteosarcoma Supervisor: Linda Viðarsdottir (linda@hi.is) Adjunct Lecturer at the Faculty of Medicine of the University of Iceland Osteosarcoma is an aggressive malignancy that predominantly affects children and young adults. Unfortunately, in the past three decades there have been no major breakthroughs in the treatment of osteosarcoma and the survival rate has reached a plateau. Therefore, there is an urgent need to further our understanding of the biology of osteosarcoma. In our group we aim to elucidate the function of noncoding RNAs. Recently we have observed that the expression of the long noncoding RNA FGD5-AS1 is correlated to survival in osteosarcoma patients. Upon FGD5-AS1 depletion we see an dramatic effect on the intracellular pathways; autophagy and endocytosis. Furthermore, we have shown that low FGD5-AS1 levels correlate with chemotherapeutic resistance in osteosarcoma cell line. The project aims to understand how FGD5-AS1 is regulating these pathways and how it contributes to chemoresistance in osteosarcoma cell lines. We are seeking a enthusiastic student eager to acquire a range of laboratory techniques to join our group. You might also be interested in the following topics that open up in a new window when you click the links Medical Life Sciences The Icelandic Health Science Instutute The Biomedical Center facebooklinkedintwitter