Forskningsprofiler
Ole Andersen
My research takes place in collaboration with colleagues at NSM, Roskilde University, the National Environmental Research Institute (DMU/AAU), KU/LIFE, and Greenland and Denmark’s Geological Survey (GEUS). The main subject is fate and effects of persistent pollutants in soil and near coastal sediment and their interaction with physiological processes including endocrine function. The research integrates molecular biological methods (gene sequencing, expression analysis for genes involved in xenobiotic and steroid hormone metabolism) and analytical chemistry (HPLC, LC-MS, GC-MS).
Student experiments can be within the following subjects:
- Biokinetics of persistent toxins in infaunal invertebrates - bioavailability.
- Interactions between sediment associated persistent compounds and infauna.
- The fate of persistent compounds – mainly PAC’s – in polluted soil.
- Biochemical and molecular characterization of phase 1 and phase 2 metabolism of persistent toxins in invertebrates (only master thesis).
The subjects are most suited for combination with chemistry and/or molecular biology.
- Toxicokinetics, bioavailability: Laboratory experiments can be set up to study relations between bioavailability and physicochemical characteristics of persistent compounds.
- Interactions: Live organisms interact with their surroundings. Laboratory experiments can quantify effects of toxic compounds on annelid irrigation and particle mixing, and effects of this bioturbation on the transport of compounds.
- Persistent pollutants in soil: The degradation of PAC’s in various soil types is studied in collaboration with GEUS and DMU. This work has relations to bioremediation and risk assessment of polluted soil.
- Metabolism of persistent toxins in invertebrates: Enzymes involved in the metabolism of persistent compounds (e.g. PAC’s) are well characterized in mammals, but less knowledge is available about the evolution of these enzymes in invertebrates. Also, some of the enzymes are involved in hormone metabolism as well. Phase 1 and phase 2 enzymes in polychaetes, crustaceans and insects can be studied using enzymology and RNA and DNA technology (only master thesis).
Tove Atlung
My areas of expertise are molecular microbiology, bacterial physiology and genetics. My main research interests lie within two areas: regulation of the bacterial cell cycle, and regulation of bacterial gene expression. I use primarily the intestinal bacterium E. coli as model organism. In its natural environments, E. coli experiences drastically variable nutritional conditions and it is adapted through evolution to cope with many different external stress situations. The protein composition of the cell is adjusted by sensitive gene regulatory systems and the fundamental processes of growth, DNA replication and cell division are finely tuned to the nutritional conditions.
I am interested in elucidating the molecular mechanisms for control of gene expression and chromosome duplication. The most important factor for regulation of the cell cycle is the replication initiator protein DnaA, which is also a transcriptional regulator. Thus, studies of the DnaA protein and its interactions with DNA are central to my research projects and I am using a combination of genetics and biochemistry as well physiological experiments in these studies. The DnaA protein is universal to the bacterial kingdom and is therefore an obvious target in the search for new antibiotics to combat bacterial infections. Recently another transcriptional regulator NrdR which is found in almost all bacterial species, was discovered. NrdR regulates expression of the essential ribonucleotide reductase genes, and my current research is focused on the signals that NrdR is responding to and its interplay with DnaA in the gene regulation.
Current and future projects:
- Transcriptional regulation of the nucleotide reductase genes
- Requirements for cooperative binding of DnaA to efficiently titrating DNA sequences
- Cellular localization of DnaA protein
- Cellular localization of different domains of the chromosome
- Evolution of gene organization of the bacterial chromosome
- Establishment of systems for screening compounds for interfering with DnaA function
I can supervise master projects in molecular and medical biology in the subjects described above, as well as collaborative projects within subjects of chemistry and environmental microbiology, and literature projects in most areas of bacteriology or cell cycle control.
I can mediate contact to projects at Statens Serum Institut, DTU food, DTU Systems biology and at NOVO-Nordisk and Novozymes.
Henning Bjerregaard
Research: My research area covers 1) hormonal signalling mechanisms in cells, 2) regulation of ion transport across cell membranes, 3) cellular calcium metabolism and 4) mechanism behind cell death. For that purpose I use model systems of tight epithelia (kidney cell culture (A6 cells)) in order to investigate the effect of hormones on sodium and chloride transport mediated by intracellular messengers (cAMP, inositol triphosphate (IP3), calcium or diacylglycerol). Furthermore, these epithelia model systems are used to explore the cellular mechanism by which toxic agents affect ion transport systems in cell organelles (endoplasmic reticulum and mitochondria) and in cell membranes of epithelia.
Louise Dalgaard
The research interests of the Diabetes and β-cell biology Group focuses (not surprisingly) on diabetes mellitus and the insulin secreting β-cell, which is located in the Islets of Langerhans in the pancreas. During development of type 1 diabetes pancreatic β-cells are destroyed by an autoimmune attack leading to complete destruction of β-cells. In the course of development of type 2 diabetes mellitus β-cells are progressively lost due to over-exertion and failure to increase insulin secretion to the metabolic demands of the body.
MicroRNA is a new research interest of the lab. MicroRNAs are tiny 21-23bp single-stranded RNAs that the cell endogenously express. MicroRNA act as transcriptional or translational repressors by binding to mRNA targets. MicroRNA therefore acts as an extra layer of gene-regulation on top of the normal gene-regulation by transcription factors and cellular signalling. The lab is interested in the role of miRNAs in β-cell development and β-cell function.
The lab has several projects that focus on the molecular events leading to β-cell failure during development of Type 2 diabetes mellitus.
- The transcription factor HNF-4α is involved in development of type 2 diabetes, and we are interested in identifying and characterizing novel target genes of HNF-4α.
- MicroRNA expression in highly differentiated islets of Langerhans compared with less differentiated β-cells
- Regulation of specific microRNAs and their role for β-cell intracellular metabolism and insulin secretory capacity'
- Role of mitochondrial anti-oxidative stress proteins for β-cell function and regulation of cell cycle, apoptosis and mitochondrial function.
- Mechanism of CD36/FAT mRNA and protein level suppression by growth hormone in β-cells. Growth hormone is one of the most potent stimulators of β-cell growth, which is mediated directly by growth hormone receptors on the β-cell.
The lab uses molecular biology techniques and cell biology tools to study the questions at hand. These include Q-PCR, cloning (expression, RNAi), promoter studies, transfection of cells, northern blotting, western blotting and RNA array-studies. In general, we use either isolated islets of Langerhans (which we isolate ourselves) or different β-cell lines for our experiments.
Håvard Jenssen
Resistance to antimicrobial agents and the limited development of novel agents is threatening to worsen the burden of infections that are already a leading cause of morbidity and mortality. This has increased interest in the development of novel strategies for design of antimicrobial drugs and compounds for selective modulation of our natural immune defences. In my laboratory we focus on development of both these classes of anti-infective drugs. The drug candidates we are working with are peptides or peptidomimetics, isolated from bacterial sources (bacteriosins) or designed from naturally occurring host defence peptides through a series of optimization strategies. Parallel to wet-lab strategies like substitution analysis and large screening libraries of peptides we employ state of the art computational in silico modelling techniques developed in collaboration with world class computer scientists, to tailor peptides/peptidomimetics with high activity and specificity. The microbial target we focus on is predominantly multi-drug resistant bacterial strains and different clinically relevant virus. The pathogens are either targeted directly (classical antimicrobial peptide drugs) or through host cell immune stimulation (classical innate defence regulators). Both branches requires an in depth mechanistic understanding of how the peptides/peptidomimetics facilitate their activity, involving a wide panel of sophisticated in vitro experiments. Pending the pathogen of interest in vivo models are designed and carried out in collaborations with expert scientists around the world. To complement the peptide design and biological evaluation effort, we are also investigating several different delivery systems, e.g.; liposome, micro-spheres, hydro-gels, nano-capillar tubes and tethering strategies.
Current projects include:
- Design and evaluation of immune modulatory peptides
- Optimization of peptides with anti-inflammatory properties and evaluation of their ability to protect against herpes simplex virus infection
- Evaluation of pros and cons by moving from peptide to peptidomimetic drug candidates
- Delivery strategies for peptides carrying wound healing properties
- Cost-effective expression and purification of host defence peptides
- Advancing in silico quantitative structure activity relationship modelling of peptide activities
Anders Blomkild Lorentzen
In the Molecular Genetics and Epigenetics Laboratory (MoGEL) we work in the fields of genetics and epigenetics and within both research areas the primary aim is to increase our knowledge of eukaryotic gene regulation and expression. We are very interested in how failures in regulatory mechanisms controlling gene expression can cause diseases, such as cancer.
A central part of our research is trying to understand how epigenetic modifications can cause inactivation of gene expression in cancer. Looking at promoter methylation, methyl-CpG binding proteins and histone modifications our hope is to increase our understanding of epigenetic gene silencing.
Our laboratory offers several projects in the fields of both genetics and epigenetics and we invite students to contact us for further information on current projects or a discussion of performing a project of your own idea (e.g. speciale/Master’s project).
Current projects
- Epigenetic analysis of specific gene promoters
- Functional analyses of the NDRG2 gene and genetic mutants
- Expression profiles of specific cancer related genes
The lab uses a broad range of molecular biology techniques and cell biology tools to study the questions at hand. These include qPCR, cloning, RNAi knockdown, promoter studies, transfection and treatment of cells, western blotting, chromatin immunoprecipitation, methylation specific-PCR and bisulfite-sequencing.
Cathy Mitchelmore
Molecular characterisation of novel genes involved in Alzheimer’s disease and cancer.
The hippocampus is the structure in the mammalian brain that is responsible for learning and memory. Cell loss in this region occurs in Alzheimer’s disease. My research group has identified several novel genes that are expressed in hippocampal neurons. One of these is a transcription factor called HOF. Another is NDRG2, which is a putative hydrolase that is up-regulated in Alzheimer’s disease and down-regulated in many cancer types, including brain tumors and colon carcinoma.
We use a range of molecular, cellular, and transgenic techniques to study the mechanisms by which these novel genes function during neuronal development and disease. For example, we investigate apoptosis, cell growth and/or reporter gene activity in mammalian neuronal cell-lines which have been forced to make large amounts of HOF or NDRG2 protein.
The main projects in my group are:
- Cellular localisation and function of NDRG2 in transfected cells and in transgenic mice.
- Identification of interacting proteins with the yeast 2-hybrid system.
- Promoter structure and alternative splicing of newly identified genes.
- Tissue expression and function of novel Alzheimer’s disease-associated genes.
Hans Ramløv
My research interests are revolving around physiological and biochemical adaptations to cold and drought in ectothermic animals. The research includes, membrane/cryoprotectant interactions, water balance in invertebrates, antifreeze protein and ice nucleation protein structure and function, cryptobiosis in tardigrades, physical chemistry of cryoprotectants. At present we are working on the following projects: Ice crystal growth patterns and the function/structure relationships in solutions of antifreeze proteins from the barkbeetle Rhagium mordax and the eel pout Zoarces viviparus. Purification and characterization of antifreeze proteins from Rhagium mordax and Zoarces viviparus. The antifreeze protein research has also deviated into areas of industrial applications of these proteins. Cryptobiosis in the eutardigrade Richtersius coronifer is investigated in the context of DNA repair, oxidative damage and protection, characterisation of ion channels in storage cells and osmoregulation as well asI interactions between sugars and selected cells from this animal. Freezing tolerance is investigated in the Siberian salamander Salamandrella keyserlingi and the frog Rana arvalis.
Ole Skovgaard
My research interests are within 1) control of DNA replication in bacteria, 2) prokaryotic gene regulation and molecular genetics, 3) molecular evolution and 4) bioinformatics.
A bacteria needs to sense when to start its duplication of the chromosomal DNA, so that two full chromosomes are ready, when the cell divides into two daughter cells. In fast growing bacteria duplication may take more than two doubling times, so it is actually the grand-grand mother cell that decides when to replicate the chromosomes for the newborn bacterial cell. The central actor in sensing when to start DNA replication is the DnaA protein, which I have studied in E. coli and other bacteria. Recently we have studied the control of DNA replication in Vibrio cholerae. V. cholerae has two chromosomes in contrast to related bacteria which only have one chromosome.
We are currently studying how to utilize conservation information to improve the precision of gene predictions in large scale analysis of genomes. Further I wish to improve prediction of the origins of genes and the distribution of genes in different organisms. The results will improve predictions of gene functions.
I’m also engaged in projects related to Next Generation sequencing. A whole new generation of DNA/RNA sequencing platforms is emerging these years. These techniques will eventually pave the road towards the “$1000 per genome” goal One of the major new techniques – the Illumina Solexa technology – generates an immense amount of short sequence reads, which on one side opens up for new interesting applications of sequencing and on the other side provide new computational challenges. I have a new and simple concept for the analysis of these sequence data.
Jesper Troelsen
The mammalian organism relies upon the gastrointestinal tract for the proper digestion and absorption of nutrients. The constant use of the cells takes a big toll on them and it is therefore necessary to have most of the mature cells renewed within a few days. The high cell turnover makes it a good system to study cell proliferation and differentiation. The intestinal epithelium continuously renews its cells by division of a stem/progenitor cell population located in the crypts. In the small intestine the daughter cells rapidly expand by cell divisions and migrate from the crypt to villus. The cells finally differentiate into the mature cell type of the intestine. In the small intestine these cells are enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. In the colon only two cell types are formed: colonocytes and goblet cells. Cells located in the bottom of the crypts are undifferentiated and proliferate (except for the Paneth cells, which are located in the very bottom of the crypt). The cells located in the upper crypt and on the villus are differentiated and express digestive enzymes, transport proteins, mucins, or hormones, depending on the cell type. In our group we focuse on the gene-regulatory mechanisms behind normal and pathological development. Presently our research projects are focused on the role of intestinal transcription factors in normal cellular differentiation of stem cells, and in colon cancer and inflammatory bowel disease (Crohns and ulcerative coilitis).
Ole Vang
The risk of various life-style related diseases in humans may be reduced by increasing the intake of fruit and vegetables. Edible fruit and vegetables contain various bioactive compounds which are found to reduce the risk of cancer, coronary-heart disease, diabetes etc (at least in experimental models). But the molecular mechanism of the effect of these compounds is only hardly known and the focus of the research in my Lab is to identify the molecular mechanisms of action of primarily three groups of naturally occurring compounds:
- Glucosinolates, especially the indolylglucosinolates, which is solely found in cruciferous vegetables (cabbage, broccoli, Brussel sprouts etc.) and these are shown to reduce several cancer forms in animal models. In humans, intake of cruciferous vegetables is linked to reduced risk of several cancer types. The indoles are known to modulate xenobiotic metabolism and the cell cycle at various stages and by this inhibits cell proliferation
- Flavonoids: These compounds are found in nearly all fruits and vegetables and the intake of the flavonoids is related to lower risk of cancer and coronary hearth disease. Their biological effects may be related to their anti-oxidant activity but they do also modulate various signalling cascades in the cell.
- Vineferins: Resveratrol is a famous compound belonging to the group of vinferins and is found in berries, peanuts, grapes and by this in red wine. Resveratrol have anti-inflammatory activity and modulate several inflammatory-related diseases, including cancer, diabetes.
Present research projects are focusing on:
- Efect of crude extracts (vegetables, fruits, or diverse plants) and pure compounds (phytochemicals) on the metabolism of xenobiotics (incl. procarcinogenic compounds): Most carcinogenic compounds need to be converted in the body before they become carcinogenic. During this conversion several reactive metabolites are formed, which interact with the DNA and cause DNA-damage etc. and ultimately cancer. We therefore investigate the modulation of the phytochemicals (and extracts) on the enzyme systems converting the carcinogenic compounds.
- Proliferation of cells with relevant DNA-damage is a crucial step in the process of carcinogenesis. One relevant effect of the bioactive phytochemicals is the inhibition of cell proliferation, which may be caused by modulation of various signal transduction pathways (NF-κB- and Akt-mTOR-pathway etc.), cell adhesion and/or enhanced intercellular communication. These analyses include investigation of expression of and activity of specific steps in the cellular cascades.
- The effect of crude extracts (vegetables, fruits, or diverse plants) and pure compounds (phytochemicals) on inflammation: ow-grade inflammation (chronic inflammation) seems to be relevant for the development of several of the big life-style diseases, as cancer, diabetes and coronary-hearth disease. Several of the dietary components we are working with reduce specific markers for low-grade inflammation.
- Identification of new methods to identify the biological activities and levels of crude extracts (vegetables, fruits, or diverse plants) and pure compounds (phytochemicals)
These investigations are done in collaboration with national and international research groups but do also include other scientists at NSM (primarily in Molecular and Medicinal biology and Chemistry).