15 ECTS projekter E2021:
1. Group leader and supervisor: Maria Andreasen ([email protected]) Project title: Effects of PSM peptides on biofilm associate MRSA infections Description:
The infective ability of the opportunistic pathogen Staphylococcus aureus, also known as methicillin-resistant S. aureus (MRSA), is directly linked to biofilm mediated resistance to host immune response and antibiotics. The structural component of biofilms is comprised of aggregated phenol-soluble modulin (PSM) peptides and the occurrence of these renders the biofilm impossible to disassemble, and hence it also becomes impossible to treat the infection pharmacologically. Using fluorescence plate-reader techniques along with biophysical techniques such as transmission electron microscopy, circular dichroism and microdiffusion the effects of PSM peptides in the MRSA biofilm is studied.
2. Group leader and supervisor: Sâmia Joca ([email protected]) Project title: Targeting cannabinoids to treat depression
Description:
We have demonstrated cannabidiol, a non-psychoestimulant compound extracted from Cannabis sativa, induces antidepressant effect in animal models, both stress-induced and genetic models. In this project we aim to investigate which brain regions are involved in such effect and evaluate gene expression and protein changes induced by cannabidiol and other cannabinoids. Drugs will be administered to animals that will be submitted to stress models of depression and the brains will be harvest for further analysis (qPCR, WB, ELISA, immunohistochemistry).
3. Group leader and supervisor: Jeppe Prætorius ([email protected]) Project title:
Initial characterization of single domain antibodies against the Na+-dependent Cl-/HCO3- exchanger Ncbe Description:
Antibodies raised by camelids, such as Llama and Alpaca, include single domain antibodies (SDA). SDA are much smaller peptides than the broadly applied IgG, as they almost only contain the antigen binding domain. Successful development of SDA against Ncbe would therefore allow for in vivo and perhaps even clinical application of the antibodies when targeting or visualizing this transporter. Ncbe is expressed widely in the CNS, but most abundantly and accessibly in the choroid plexus, where it forms part of the CSF
secretion apparatus. Antibodies are currently being developed in 3 camelids in California and are expected to be ready for antibody validation by summer 2021. We are looking for an enthusiastic and persistent medical student to run the initial part of the validation including immunohistochemistry, immunoblotting, and confocal microscopy, and proof of in vivo targeting the choroid plexus by i.v. injections of fluorescent SDA.
4. Group leader and supervisor: Jeppe Prætorius ([email protected])
Project title: Mapping the early proximal tubule regarding water and salt transporters: basis for apparent isosmotic reabsorption
Description:
The very first cells of the rodent renal proximal tubule (PT) do not express the water channel AQP1 in contrast to the described ion transporters. The working hypothesis is that the morphological discrepancies
to generate a small but essential osmotic gradient across the tubule allowing for osmotic water movement in the latter parts of the PT. Interestingly, the early PT cells are equipped with a thickened basement membrane compared to all other renal tubules, which may help build up of a hydrostatic pressure in the lateral intercellular space necessary for isosmotic reabsorption. In this project, we wish to 1) establish a similar focal lack of AQP1 in the very early PT in the human kidney, 2) verify that the early PT is also
equipped with the thickest basement membrane, and 3) compare cell volumes in early to late PT in kidneys from normal and AQP1 ko mice by immunohistochemical analysis of paraffin embedded tissue from mice, rats and humans and confocal microscopy.
5. Group leader and supervisor: Karina Dalsgaard Sørensen, MOMA ([email protected])
Project Title: Circulating tumor DNA analyses of prostate cancer – interference from clonal hematopoiesis? Description:
The project aims to assess to which extend clonal hematopoiesis may interfere with liquid biopsy based genetic analyses of prostate cancer for use in precision medicine. You will analyze existing DNA sequencing data generated by deep-targeted NGS analyses of cell-free DNA isolated from plasma samples and from matched peripheral blood cell samples from prostate cancer patients. This will allow you to identify mutations that are derived from prostate cancer tissue vs. clonal hematopoiesis. Good computer skills and an interest in programming/bioinformatics will be an advantage.
6. Group leader: Jelena Radulovic ([email protected]) Supervisors: Naoki Yamawaki and Asami Tanimura
Project title: Examine the distribution of axons from subcortical neuromodulatory system in hippocampus Description:
Neuromodulators powerfully impact neuronal activity and communication required for memory. Therefore, their dysfunction often leads to disorders associated with memory impairments. The aim of this project is to assess how projections from neuromodulatory systems are distributed in hippocampus, a key brain area involved in memory formation. Methodologically the project primarily utilizes sectioning and
epifluorescence imaging of fixed mouse brain. We plan that 2 students work on the same project. 7. Group leader and supervisor: Joanna Kalucka ([email protected])
Project title: Metabolic adaptations in the liver endothelial cells during obesity. Description:
Obesity is a growing problem worldwide. Impaired vascular remodelling, during development of obesity, promotes hypoxia and inflammation leading to increasing occurrences of obesity-related disorders
including cardiovascular disorders. Therefore, malfunctional blood vessel has become a clinically recognized as life-threatening incidence in human. Given the emerging importance of understanding the biology of endothelial cells (ECs) (the building blocks of blood vessels) in different tissues, by using a molecular approach like: EC cell culture, qPCR, Western Blot and immunohistochemistry, we aim to characterize liver endothelium. The aim of our studies is to provide the answers on what kind of impact the microenvironment represented by the obese state has on the protein and gene expression in liver endothelial cells.
8. Group leader and supervisor: Nicolai Birkbak, MOMA ([email protected]) Project title: Explore the role of clinical parameters in the evolution of cancer metastasis Description:
Most cancer deaths are caused by metastatic cancer. This project aims to assess the relevance of clinical and metabolic factors in relation to development of metastatic cancer. You will be given access to public datasets containing clinical information on cancer patients, as well as their diagnosis, treatment, and outcome. Your task is to investigate specific hypotheses related to the onset of cancer metastasis, such as the role of obesity, metabolic alterations, and inflammation. Further molecular analysis may be performed as well, considering the role of specific cancer somatic mutations. The project is based on data analysis, and involves extensive work with excel and/or R. Good computer skills and an interest in bioinformatics will be an advantage.
9. Group leader and supervisor: Claus H. Gravholt, MOMA ([email protected]) Project title: Exome sequencing of patients with genetic endocronologic disease
Description:
Investigation of the diagnostic advantage of exome sequencing of patients suspected of endocronologic disease. We have performed exome sequencing for a number of years and analysed material from 150 patients. The project involves evaluation of the results with further bioinformatic exploration of data.
10. Group leader: Vivi Schlünssen ([email protected]) Supervisor: Christine Cramer
Project title: A long-term follow-up study of pigeon breeders
Description: Pigeon breeders are in an environment rich in microbial exposure and organic dust, thus making them an ideal population for investigating the possible positive and negative health-effect of such exposures.
The database is the largest of its kind worldwide. We have register data on 7000 pigeon breeders, equaling 140.000 person-years, followed from 1980 until 2013. Their 1:50 controls have been matched on birth year and sex. We have data on diagnoses given in hospitals and out-patient clinics, as well as on prescription medicine and possible confounders.
In this project you will have the opportunity to influence the choice of study outcome. 11. Group leader: Tomonori Takeuchi ([email protected]) Supervisor: Kristoffer Højgaard
Project title: Proteins of memory function Description:
The project will be aimed at identifying proteins involved in memory function. Based on the Synaptic tagging and capture hypothesis, we will identify plasticity related proteins that are specifically involved in dopamine induced enhancement of memory retention. Depending on the student, the project could involve behavioral studies on rats and/or immunohistological studies, looking at the expression of target proteins
12. Group leader and supervisor: Søren Besenbacher, MOMA ([email protected]) Project title: Detecting genes where de novo mutations cause disease.
Description:
In this project, you will use newly developed software to find genes where de novo mutation causes disease. The software will be tested on public data sets, and you will compare the results with previously published studies. The software can compare the observed number of non-synonymous de novo mutations
subdividing the non-synonymous mutations using information from public databases. Good computer skills and an interest in programming/bioinformatics will be an advantage.
13. Group leader and supervisor: Lars Dyrskjøt Andersen, MOMA ([email protected])
Project title: Tumor microenvironment (TME) and its role in bladder cancer progression and treatment response
Description:
The project aims to identify immune cell compositions in the TME that are associated with clinical and histopathological parameters, disease outcome, and that affects treatment efficacy. You will analyze existing multiplex immunofluorescence images and/or derived image data that identify various immune cells and carcinoma cells from >500 patients with early and late stage bladder cancer. Good computer skills and interests in programming and human cell biology will be an advantage.
14. Group leader and supervisor: Claus Lindbjerg Andersen, MOMA ([email protected])
Project title: Circulating tumor DNA (ctDNA) analyses of colorectal cancer – the impact of genome doubling on ctDNA detection ?
Description:
The project aims to assess to which extend cancer cell genome doubling impacts detection of tumor DNA in the circulation, and thereby how it influences liquid biopsy based genetic analyses of colorectal cancer for use in precision medicine. You will analyze existing whole exome tumor DNA sequencing data to identify the subset of colorectal cancer patients whose tumors have undergone genome doubling and next you will investigate if this characteristic, which in essence should mean that each cancer cell releases twice the normal amount of tumor DNA, impacts the ability to detect tumor DNA. The latter you will do by analysis of likewise existing deep-targeted next generation sequencing data from matched plasma cell-free DNA. The exome data will allow you to both assess genome doubling and identify the tumor specific mutations that will used as markers to assess if a fraction of the cell-free DNA in the patients plasma are of tumor origin. Good computer skills and an interest in programming/bioinformatics will be an advantage.
15. Group leader: Holger Brüggemann ([email protected]) Supervisors: Phd student Mastaneh Afshar and Holger Brüggemann
Project title: Antimicrobial resistance among skin-resident coagulase-negative staphylococci Description:
Antibiotic resistant bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) are a global threat to human health. MRSA are found on human skin, but little is known about the resistance profile of other, more abundant skin-resident staphylococci, i.e. coagulase negative staphylococci (CoNS). Here, CoNS strains isolated from human skin are investigated regarding their antimicrobial resistance profile.
Techniques used in this project are bacterial cultivation, DNA extraction, whole genome sequencing (WGS) and WGS analyses, as well as the determination of resistance to selected antibiotics with Minimum
Inhibitory Concentration (MIC) assays.
16. Group leader and supervisor: Simon Fristed Eskildsen, CFIN ([email protected]) Project title: Biomarker systems in Alzheimer’s disease: can a vascular component add value to the amyloid-tau-neurodegeneration system?
Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. Therefore, an unbiased descriptive classification scheme for these biomarkers have been suggested based on amyloid, tau, and neurodegeneration – the so-called A/T/N system. This system focuses on established biomarkers of AD and is useful for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use for clinicians.
Recently, researchers have become aware that the vascular system plays a previously neglected part in the pathophysiology of the disease. At Center of Functionally Integrated Neuroscience, we investigate the role of perfusion and the microvasculature in AD and acquire neuroimaging data in patients as part of our research. This has led to potentially novel vascular-based imaging biomarkers of AD.
In this project, you must apply the A/T/N system to a cohort of patients with mild cognitive impairment (MCI) and test if the system can be extended with a vascular biomarker so it becomes A/T/N/V. To do this, cut points need to be established for each biomarker using the literature and examining the data acquired from the MCI cohort. Similarly, cut points for a new vascular biomarker component must be established. Changes in the A/T/N/V labeling of the MCI patients over two years is observed and related to the
pathophysiology. Data for the established and novel biomarkers will be made available in the project. This is a combined literature and data analysis project. The students can apply statistical models in the work, but this is not mandatory.
17. Group leader and supervisor: Simon Fristed Eskildsen, CFIN ([email protected]) Project title: Prediction of Alzheimer’s disease using neuroimaging and clinical data
Description:
The ability to diagnose and predict Alzheimer's disease (AD) at an early or even pre-clinical stage has great impact on the possibility for improving treatment choices of the disease. In addition, accurate prediction may also guide the selection of patients for disease modifying interventions when performing large-scale trials, since false positives reduce statistical power and are very costly for these trials. In this project, your task is to predict AD in subjects suffering from mild cognitive impairment (MCI). For this purpose, you will get access to large public datasets of MCI patients were the disease progression is known. The datasets consists of imaging biomarkers based on PET and MRI, blood- and CSF biomarkers, and cognitive tests. The aim is to find a combination of biomarkers and tests that accurately predict AD. This is a data analysis project and requires extensive work with statistical models and/or machine learning. Good computer skills and an interest in bioinformatics will be an advantage.
18. Group leader and supervisor: Brian Hansen, CFIN ([email protected]) Project title: Preclinical MRI of awake animals
Description:
Animal models are used extensively in biomedical research. In neuroscience preclinical MRI is often used to investigate brain state. These investigations are typically performed in anesthetized animals but recent work shows that animal physiology is perturbed by the anesthetics thereby potentially contaminating results. To avoid this effect we are working on establishing awake animal MRI. The project will introduce the student to the methods used in preclinical MRI, the training and handling of animals for awake MRI and the research potential of this approach.
19. Group leader and supervisor: Lise Juul, Dansk Center for Mindfulness ([email protected]) Project title: Mental health in Danish schoolchildren
In spring 2020, a total of 1151 schoolchildren in grade 4 – 9 completed a questionnaire including a variety of validated scales measuring mental health (well-being, mental health problems, resilience and
mindfulness). The data was collected in municipal and private schools from the Capital Region of Denmark, Region Zealand and Central Denmark Region.
The aim of your project could be to i) describe mental health in Danish schoolchildren in spring 2020 and ii) to investigate associations between different aspects of mental health.
20. Group leader and supervisor: Sine Skovbjerg, Dansk Center for Mindfulness ([email protected])
Project title: Mental health in the adult Danish general population Description:
Mental health can be defined as a state of well-being in which every individual realizes his or her potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to contribute to her or his community (WHO). Based on data from the adult general population (n= 9700) the aim of the project is to describe mental health in Denmark. Data on mental health include validated measures of perceived stress, anxiety and depression. Moreover, to explore the possible association between mental health status and sex, age, social status and education.
21. Group leader and supervisors: Brian Hansen and Eugenio Guiterrez, CFIN ([email protected]) Project title: Capillary dysfunction in Alzheimer's disease
Description:
Alzheimer's disease (AD) shares many risk factors with cardiovascular diseases, and much evidence shows that AD involves dysfunction of the brain's microcirculation. This project assesses the correlation of brain capillary blood dynamics and oxygen diffusion on the development of AD in animal mouse models. The tasks involve the analysis of functional imaging with advanced optical techniques and high-field MRI. Integration of imaging and molecular techniques is also implemented to understand the molecular mechanisms behind the hemodynamic changes.
22. Group leader and supervisors: Nina Iversen and Eugenio Guiterrez, CFIN ([email protected]) Project title: Capillary dysfunction in Stroke
Description:
Optimal management of Stroke requires an in-depth understanding of the hemodynamics, metabolic and cellular changes occurring in the brain tissue. During the stroke event, the suppression of flow produces gradual changes on the brain capillaries that tend to prevail regardless of large vessels' re-perfusion. The capillary dysfunction observed in Stroke is predicted to reduce cerebrovascular reserve capacity markedly, increasing the risk for extensive damage to the brain tissue. In this project, we examine the disturbance in capillary dynamics in animal models of hypoperfusion and Stroke. We integrate advanced optical imaging techniques and high field-MRI to evaluate the changes in capillary blood flows and oxygen diffusion to brain tissue during Stroke. The student will be introduced to the analysis of imaging data and behavior,
supporting the findings' interpretation.
23. Group leader: Peter Vuust (Center for Music in the Brain) ([email protected]) Supervisor: Kira Vibe Jespersen
Description:
Using a randomized controlled trial design, we evaluate the efficacy of music as intervention for sleep-onset insomnia. We assess the effect of the intervention using both subjective and objective sleep measures. Furthermore, we test if the effect of the music on sleep is related to the participants’
neurophysiological response to the intervention music using EEG and physiological measures of heart rate, skin conductance and respiration.
24. Group leader: Peter Vuust (Center for Music in the Brain) ([email protected]) Supervisor: Boris Kleber
Project title: The Neuroscience of human vocal-emotional communication Description:
Cognitive Neuroscience project on human vocal-emotional communication. In this project, we will use fMRI data acquisition to describe neural fingerprints of dynamic brain connectivity reflecting both emotion and motor aspects of vocal communication, as well as their interaction. Applicant would be involved in data collection, data analyses, and drafting results. Parts of these results may be included in an ongoing Master thesis, subject to agreement with Prof. Peter Vuust.
25. Group leader: Peter Vuust (Center for Music in the Brain) ([email protected]) Supervisor: Ole Adrian Heggli
Project title: The sound of depression Description:
In this project we will examine the auditory features of music stereotypically related to depression. The student will undertake a quantitative data collection of Spotify Playlists, which we will perform Music Information Retrieval on. The data will be compared to general music, and a follow-up study aiming to identify changes in music listening behaviour predictive of depression onset may be undertaken (dependent on ethical permission, and student's aptitude).
26. Group leader: Peter Vuust (Center for Music in the Brain) ([email protected]) Supervisor: Cecilie Møller
Project title: Beat induction in polyrhythms Description:
Polyrhythms are ambiguous musical rhythms: several regular beats co-exist, yet only one is heard at any given time. They are interesting to neuroscientists because perception of polyrhythms strongly depends on the way our brain interprets the sensory information. In a series of studies, we have investigated factors influencing beat perception in polyrhythms. In this study, we will develop and test the reliability of context stimuli aimed to induce perception of one or the other beat. The student will design and run short online tapping studies in R, based on thorough scrutinizing of previous data sets.
2- 3 students can work together on this project.
27. Group leader: Peter Vuust (Center for Music in the Brain) ([email protected]) Supervisor: Alexandre Celma-Miralles
Project title: Rhythmic advantages in sensorimotor synchronization Description:
Motor synchronization to a periodic sound (like the beat of a song) can be improved by introducing
motor and electroencephalographic responses (EEG, if restrictions allow) and analyze part or all of the recordings to identify any behavioral or neural advantage related to the distinct rhythms or tempi.
28. Group leader and supervisor: Deirdre Cronin Fenton, KEA ([email protected]) Project title: Type 2 diabetes and breast cancer
Description
Breast cancer survivors constitute more than 20% of cancer survivors, so it is critical to identify late effects of the disease. Type 2 diabetes may be a complication of breast cancer therapy. To advance knowledge on type 2 diabetes and breast cancer, this systematic review and meta-analysis will determine the incidence of type 2 diabetes in breast cancer patients compared with the general population, and according to breast cancer treatments.
29. Group leader and supervisor: Peter Jepsen, KEA ([email protected])
Project title: Patient characteristics and risk of complications among patients with liver cirrhosis Description
In this epidemiological study among patients with cirrhosis, students will be examining various patients’ characteristic as risk factors for selected complications. Depending on the specific question, students will have a chance to analyse simulated or aggregated data.
30. Group leader and supervisor: Christian Fynbo Christiansen, KEA ([email protected]) Project title: End-of-life care in patient with chronic kidney disease
Description
Health care utilization may very considerable at the end of life in patients with different chronic conditions. The aim of this project is to examine health care utilization during the last months of the life in patients dying from kidney disease. This will be examined through literature review and analyses of aggregated data.
31. Group leader and supervisor: Vera Ehrenstein, KEA ([email protected]) Project title: Prenatal exposure to medications and pregnancy/birth outcomes Description
Most pregnant women use prescription medication, yet safety of medicines is nearly never examined in randomized trials in pregnant populations. Reliable evidence regarding safety of treatments in pregnancy is important for women planning pregnancy, especially those who need to continue treatment after
conception. The aim of this project is to use meta-analysis to synthesize evidence about safety of selected treatment during pregnancy. The standard outcomes examined in such studies include fetal death, major congenital malformations, and intrauterine growth retardation.
32. Group leader and supervisor: Rune Erichsen, KEA ([email protected])
Project title: Prognosis after colorectal cancer originating from the serrated pathway Description
Until recently, most colorectal cancers were though to emerge through the well-described adenoma-carcinoma sequence. However, up to one-third of all colorectal cancers are now known to originate
through the serrated pathway characterized by e.g. BRAF mutations and high-level microsatellite instability. By conducting a literature review, this project aims to compare the prognosis among patients with
colorectal cancer originating through the serrated pathway vs. patients with colorectal cancer originating through the adenoma-carcinoma sequence.
33. Group leader Sarang S. Dalal, CFIN ([email protected])
Supervisors: Sarang S. Dalal, CFIN) and Lars Henning Pedersen (Obstetrics and Gynecology, AUH) Project title: Optically Pumped Magnetometers for Fetal Magnetoencephalography
Description
Fetal magnetoencephalography (MEG) is the measurement of fetal brain activity that could help monitor brain development in high-risk pregnancies, but due to its exorbitant expense, it has only been available in two labs worldwide. Optically pumped magnetometers have recently emerged as a new and far less expensive technology for measuring physiological magnetic signals, including MEG from adults and
children. This project aims to demonstrate a proof-of-concept for measurement of fetal MEG with optically pumped magnetometers. In this phase, we will make measurements with healthy low-risk pregnancies with a view towards establishing this technique for potential use in fetal medicine.
34. Group leader: Martin K. Thomsen ([email protected]) Supervisor: Justin V. Joseph
Project title: Profiling of glioma from a mouse model Description
We have establish mouse models of glioma by CRISPR. Hereby, gliomas with different gene mutations have been generated. The mice has received different treatment and the disease progression has been followed by MRi scans. This project aims to analysis the tumor samples by histology and gene expression. You will perform histological analysis by processing the samples and stain with antibodies for different proteins. The results will be complimented with gene expression performed with qPCR and Western blotting analysis
