Home  About UCMR UCMR Research Groups
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Molecular Biology
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Sven Bergström
Pathogenesis, antigenic variation and genetic organization
The overall aim of this project is to gain an increased knowledge of the virulence properties of Borrelia spirochetes. We will continue the basic research on the mechanisms of antigenic variation of Borrelia and to characterise and define the components involved in the interactions between RF Borrelia and erythrocytes as well as the effect(s) that the erythrocyte rosetting exhibit at the cellular and molecular level in the mammalian host. We will also investigate what molecules that are involved in the interactions employed by B. burgdorferi s.l., the Lyme disease agent, with different mammalian cells and tissues. As well as structural and functional studies on those outer surface located molecules.
 Read More (Sven Bergström's group at Molecular Biology
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PI: Sven Bergström
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Molecular Biology
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Our research is focused on the mechanisms of innate immunity, using Drosophila as a model system. This organism lacks lymphocytes and an acquired immune response, but has a well developed innate immune system. Studies of Drosophila have already contributed significantly to our understanding of innate immunity in humans. In addition, insect immunity is of great theoretical and practical importance in its own right, not least because insects are vectors for serious human diseases, and because insect pathogens are increasingly used to control agricultural pests.
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PI: Dan Hultmark
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Molecular Biology
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Emmanuelle Charpentier
Molecular mechanisms governing gram-positive bacterial pathogenesis
Our group is interested in the understanding of molecular mechanisms governing the interaction of gram-positive bacterial pathogens with their hosts, mainly employing the human pathogen Streptococcus pyogenes (Group A streptococcus, GAS) as a model organism. During an ongoing disease process, pathogens are heavily exposed to different specific and non-specific host defence mechanisms, amongst others growth-limiting conditions and stress factors at the site of infection. To thrive under these hostile conditions, pathogenic bacteria have developed well-directed strategies leading to a coordinated expression of virulence factors in response to host-induced environmental changes and stress. In this regard, small regulatory RNA molecules and regulated protein quality control play key roles in gram-positive bacterial pathogenesis and constitute the current research focus of our lab.
Read More (Emmanuelle Charpentier's group at MIMS)
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Molecular Biology
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The aim of this project is to clarify molecular mechanisms behind bacterial infections and to understand regulation of antimicrobial functions of host cells. Our intention is to utilize "knowledge" of pathogenic microorganisms to find critical events in host defence. Specific host cell targets of bacterial virulence proteins are identified, and function and regulation of these in infection processes are studied.
Read More (Maria Fällman's group at Molecular Biology)
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PI: Maria Fällman
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Molecular Biology
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Yersinia pseudotuberculosis is an oral bacterial pathogen capable of causing self-limiting foodborne illnesses and lingering reactive arthritis. In so doing, this pathogen serves as a model organism to study both the cause and effect of sophisticated bacterial interactions with target human cells. To dissect some of these processes is our goal. One predominate determinant of Yersinia pathogenesis is a multi-component injection device capable of targeting toxic bacterial proteins directly into the eukaryotic cell interior. We therefore delineate the various molecular interactions between components of this injection device and uncover the consequences of these interactions with respect to toxin targeting into eukaryotic cells. In addition, we also investigate the physiological relationship between maintenance of bacterial envelope integrity while assembling multi-component virulence determinants in this organelle. We currently approach this by analyzing the impact that activation of extra-cytoplasmic stress responsive pathways has on virulence gene expression and cellular pathogenesis by Yersinia.
Read More (Matthew Francis' group at Molecular Biology)
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| PI: Matthew S. Francis |
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Molecular Biology
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Our research has been focused on identification of intracellular proteins with potential functions during signal transduction and growth control, which resulted in the identification of Oncoprotein 18/stathmin (Op18). The complex pattern of phosphorylation together with the observed up-regulation of Op18 in several types of human malignancies, suggested to us that this protein may have a central role in cell signaling. We have identified the function of Op18 as a phosphorylation-responsive regulator of microtubule dynamics and linked Op18 phosphorylation to regulation of microtubule dynamics in response to both external and cell cycle signals. Identification of homologous proteins reveals that Op18 represent a prototype of a new family of microtubule regulators.
Read More (Martin Gullberg at Molecular Biology)
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PI: Martin Gullberg
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Molecular Biology
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Listeria monocytogenes is a gram-positive human pathogen causing several different diseases, like meningitis, septicaemia and abortions. Listeria has an unique ability to cross the intestinal barrier, the placental barrier and the blood-brain barrier during infection. The bacteria is able to invade most tissues and shows a specific cell-infection cycle
Read More (Jörgen Johansson's group at Molecular Biology)
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| PI: Jörgen Johansson |
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Molecular Biology
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Vibrio anguillarum constitutes part of the normal microflora of the aquatic environment and may also constitute part of the microflora of marine fish. In marine waters, V. anguillarum has shown maximal numbers in the summer months and minimal numbers in the winter months. Usually during the summer months, V. anguillarum causes a haemorrhagic septicemia in marine fish and has a great economical impact on the fish-farming industry. V. anguillarum and its fish host provide a good model for the study of host-bacterial interactions.
Read More (Debra Milton's group at Molecular Biology)
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PI: Debra Milton
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Molecular Biology
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The Gram-positive bacterium Streptococcus pyogenes is one of the most common and important human bacterial pathogens. Streptococcal infections include throat and skin infections, which, although generally self-limiting, cause substantial morbidity and economic loss for society. 600 million people are estimated to suffer from streptococcal pharyngitis world wide. Invasive streptococcal infections are rare; however, about 3000 cases of severe cases are reported every year in Europe. Streptococcal infections are commonly localized to the mucosal epithelium of the respiratory tract or to epidermal skin layers. The establishment of these infections is characterized by an intense inflammatory state, a typical feature of streptococcal infections. Host-pathogen interactions of S. pyogenes in an inflammatory environment have so far only poorly been investigated, but are of great importance as uncontrolled inflammatory responses lead to serious life-threatening conditions such as the streptococcal toxic-shock syndrome. Our research aims to elucidate the role of streptococcal proteases in controlling inflammatory processes. These mechanisms are involved in severe clinical conditions, as well as in autoimmune disorders like rheumatoid arthritis; and in dermatoses like psoriasis. Since S. pyogenes infections are clinically highly significant, studies on the molecular interaction between S. pyogenes and proteins controlling inflammatory processes are of significant importance and essential to our understanding on the impact of bacterial infections on human physiology. Importantly, these findings connect underlying molecular mechanisms of significant inflammatory diseases with microbial pathogenesis. .
Read More Ulrich von Pawel-Rammingen's group at Molecular Biology)
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PI: Ulrich von Pawel-Rammingen
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Molecular Biology
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Research interests are centered on the underlying molecular mechanism by which bacteria perceive their surroundings and how they integrate and transduce multiple and sometimes conflicting signals to effect appropriate changes in their gene expression and ultimately their behavior.
Read More (Victoria Shingler's group at Molecular Biology)
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PI: Victoria Shingler
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Molecular Biology
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Bernt Eric Uhlin
Our research is aimed at increasing the understanding of the mechanisms by which pathogenic E. coli and other enterobacteria express virulence-associated properties. We study molecular mechanisms behind expression and function of genes and gene products that contribute to the bacterial interactions with host environments.
Read More (Bernt Eric Uhlin's group at Molecular Biology)
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PI: Bernt Eric Uhlin
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Molecular Biology
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Constantin Urban
Our group "Antifungal Immunity" is interested in the fundamental processes during infections with pathogenic fungi. We combine studies on how the innate immune system restricts the spread of fungal pathogens and how these microbes in turn react to the host environment.
Read More (Constantin Urban´s group at Molecular Biology)
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PI: Constantin Urban
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Molecular Biology
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There are three human pathogenic strains of Yersinia; Y.pestis , Y.pseudotuberculosis and Y.enterocolitica . Y.pestis is the causative agent of plague; and was responsible for the Black death during the 14th century. This family of bacteria harbours a common virulence plasmid which encodes a number of secreted proteins collectively called Yops (Yersinia outer proteins). These proteins are expressed during infection and they are major antihost factors.
Read More (Hans Wolf-Watz's group at Molecular Biology)
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PI: Hans Wolf-Watz
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Molecular Biology
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The regulated expression of different virulence factors and the physiological adaptation to changing environmental conditions are essential for the ability of bacterial pathogens to cause infection and disease. In my research group we are studying Vibrio cholera and Escherichia coli as model organisms to elucidate molecular mechanisms behind virulence factor expression and host interactions.
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| PI: Sun Nyunt Wai |
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Clinical Microbiology
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Signal Transduction in Host-Microbial Interactions and Inflammation
Nelson Gekara
The innate immune system provides the first line of defense against microbes and other foreign substances. Innate immune detections of and responsiveness to microbes is mediated by sets of receptors known as pattern recognition receptors (PRRs). Our research is interested in understanding the mechanisms that govern the regulation of signaling pathways of microbe recognition receptors of the innate immunsystem.
Read More (Nelson Gekara's group at MIMS)
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PI: Nelson Gekara
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Clinical Microbiology
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Anna Överby
Tick borne encephalitis virus
Tick borne encephalitis virus (TBEV) is an important emerging human pathogen. The virus infection causes a broad spectrum of symptoms ranging from mild infections to more severe symptoms such as meningitis, encephalitis, and hemorrhagic fever associated with high mortality rates. The severity of the symptoms is strain dependent.
Whereas TBEV strains from Central Europe often cause milder disease, strains from Siberia and Far Eastern frequently lead to more severe symptoms. The molecular mechanism underlying this virus strain dependency remains elusive. Therefore, we are interested in identifying potential molecular strain differences and correlating them with pathogenicity.
Specific antiviral drugs are still not available and treatment of patients is limited to supportive care only. Although an effective vaccine is available, the number of clinical TBE cases is increasing both in Sweden and all over Europe.
Read More (Anna Överby's group at MIMS)
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PI: Anna Överby
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Clinical Microbiology
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The main goal of our project is to learn more about the early events in virus life cycle. We want to identify and characterize components and mechanisms that regulate virus (adenovirus, picornavirus and influenza A virus) binding to and entry into target cells.
Read More (Niklas Arnberg's web page at MIMS)
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PI: Niclas Arnberg
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Clinical Microbiology
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Diagnosis of tularemia tradionally relies on cultivation, PCR and serology, but there is still a need to improve the diagnostic possibilities, e.g., with regard to speed and prognostic markers. Moreover, some patients present with uncharacteristic symptoms and are therefore difficult to diagnose. The relatively high number of samples handled by the laboratory means that the laboratory staff may be exposed to the bacterium during routine work and since it is highly contagious, being at risk to contract tularemia. Therefore, improved assays that allow very rapid diagnosis are of high priority. We will now develop methods based on the characterization of the host response or secreted bacterial factors as rapid diagnostic tools that also can have prognostic potential. Moreover, we will develop very rapid methods for identification and typing of the bacterium to enhance the laboratory safety.
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PI: Anders Sjöstedt
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Clinical Microbiology
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The murine retroviruses and human adenoviruses are the two most frequently used viral vector systems The murine retrovirus system is versatile. Limitations: . Safety and no access to non dividing cells. The Ad5 vector can not efficiently transduce hematopoietic cells. Ad5 is pathogenic and persistent for several years in children. The prevalence of immunity against Ad5 is high. An anamnestic immune response is seen upon administration of Ad5 vector which impairs a sustained expression of the transgene.
Adenivirus Vectors for Haematopoietic Cells
Hematopoietic cells are attractive targets for gene-therapy. However, no satisfactory adenoviral vectors are currently available. A major problem with the most commonly used adenovirus (Ad) vectors, based on either Ad2 or Ad5, is their low binding efficiency for hematopoietic cells which do not express the coxackie adenovirus receptor (CAR). Ad2 and Ad5 and several other Ad serotypes use CAR as a primary attachment receptor. However, far from all adenoviruses uses CAR as a receptor. In our search for adenovirus serotypes that would make efficient vectors for hematopoietic cells we have identified two Ad serotypes, Ad11p and Ad35p, that binds very well to all kinds of hematopoietic cells. I have so far studied the interaction of these serotypes with different committed hematopoietic cell lines, i.e. their ability to bind and infect.
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PI: Göran Wadell
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Medical Biochemistry and Biophysics
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THE GASTRIC PATHOGEN Helicobacter pylori infects the human stomach of more than half of the world’s population and represents one of the most frequent causes of inflammatory processes in the stomach. The association of H. pylori infection and development of peptic ulcer disease and gastric cancer is well established.
ADHERENCE to the gastric epithelium is important for colonization and to establish a chronic infection. The gastric milieu changes during pathogenesis and H. pylori use different adherence proteins (adhesins) for interaction to healthy and inflamed gastric epithelium. The focus of our research is the mechanisms that are involved in the ability to adjust adhesin expression levels and the properties to cycle between an adherent and a non-adherent phenotype. We use the adhesin-receptor interactions, BabA and its interaction to ABO blood group antigens and the SabA adhesin and its interaction to the inflammation-associated receptor structures sialyl-Lewis x/a antigens.
Read More (Anna Arnqvist's group at Medical Biochemistry and Biophysics)
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PI: Anna Arnqvist
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Medical Biochemistry and Biophysics
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Helicobacter pylori infection causes chronic active gastritis and peptic ulcer disease. In the western world, 10% of people (22.000.000 individuals) develop peptic ulcers. Furthermore, H. pylori infection is tightly correlated with development of gastric cancer with >500.000 mortalities/Y and, H. pylori has been defined a carcinogen by the WHO. The project studies protein-carbohydrate interactions that mediate adherence of H. pylori to stomach tissue. We focus on the Blood Group Antigen Binding Adhesin, BabA, which is the key player attachment protein that targets H. pylori binding to the stomach lining.
Read More (Thomas Borén's group at Medical Biochemistry and Biophysics)
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PI: Thomas Borén
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Medical Biochemistry and Biophysics
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Andrei Chabes
Genetic information in most organisms is stored as DNA. DNA is synthesized from four building blocks, dNTPs. The DNA is constantly damaged either spontaneously or by environmental agents. If the damaged DNA is not repaired, it acquires mutations. Some mutations may cause genetic instability and cancer.
In eukaryotes, DNA damage leads to arrest of cell cycle, transcriptional activation of DNA repair genes, and apoptosis. These responses allow cells to survive the damage and repair the DNA.
Read More (Andrei Chabes' group at MIMS)
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PI: Andrei Chabes
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Medical Biochemistry and Biophysics
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Ribonucleotide reductase (RNR) plays a central role in the formation and control of the optimal levels of deoxyribonucleoside triphosphates, which are required for DNA replication and repair. In eukaryotic cells, both enzyme activity and the mRNAs encoding the two non-identical subunits, proteins R1 and R2, are cell cycle regulated with maximal levels during S phase.
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(Lars Thelander's group at Medical Biochemistry and Biophysics)
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PI: Lars Thelander
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Chemistry
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Design, Synthesis & Evaluation of Ring fused 2-Pyridones Directed at Different Medicinal Targets and Diverse Oriented Synthesis (DOS) Towards New Heterocyclic Scaffolds.
A chemical platform with broad applications and flexibility has been rationally designed to interrupt complicated molecular machines important in microbial pathogenesis. The research programme contains a blend of computer-aided design, synthetic organic chemistry, molecular biology and genetics to investigate and disrupt complex biological systems important in disease processes.
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PI: Fredrik Almqvist
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Chemistry
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The research projects cover many aspects of organic chemistry with the aim to utilize small molecules to answer large questions in biology. The group is currently engaged in two major areas: solid-phase glycoconjugate synthesis and type III secretion inhibitors. The glycoconjugates are used in array applications with the aim to study microbial attachment. Type III secretion inhibitors can be used a stools to study bacterial virulence and as starting points for development of anti-infective drugs.
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Laboratories for Chemical Biology Umeå (LCBU)
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PI: Mikael Elofsson
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Chemistry
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The human tetrameric thyroid hormone-binding protein transthyretin belongs to a group of over 20 proteins that to cause disease by the formation of insoluble fibrils called amyloids. TTR is associated with two medical disorders: familial amyloidotic polyneuropathy (FAP) caused by mutations within the protein, and senile systemic polyneuropathy (SSA) that involves the native protein. FAP is prevalent in the northern parts of Sweden, where it is also referred to as "Skelleftesjukan". Amyloidosis involves structural changes within the amyloidogenic protein.
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| PI: Elizabeth Sauer-Eriksson |
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Chemistry
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The aim of the work in my group is to understand the underlying physical principles of biomolecular organization and recognition. At the moment we focus on the following major areas: Proteins involved in nucleotide recognition (DNA, RNA and free nucleotides) and proteins involved in muscle assembly.
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| PI: Uwe Sauer |
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Physics
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Research is pursued in two partly interdisciplinary fields of science: The first is concerned with the development of new and powerful laser-based spectroscopic techniques for sensitive and selective detection of various types of molecular species in gas phase (often of environmental or toxicological interest) under a variety of conditions, primarily for applications such as environmental monitoring, process control chemical analysis, and combustion diagnostics. Of special importance is the development of diode laser based and/or cavity enhanced absorption techniques with improved detection and selection capabilities, in particular IR and UV TDLAS (tunable diode laser absorption spectrometry) and NICE-OHMS (noise-immune cavity-enhanced optical heterodyne molecular spectrometry). The second field is mainly concerned with development of optical tweezers for non-intrusive manipulation of micrometer-sized biological objects (individual cells and bacteria) and for force measurements in biological systems. This field includes also investigations and modeling of the biophysical properties of individual macromolecules, primarily bacterial pili, exposed to strain and/or stress.
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PI: Ove Axner
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Physics
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In Dynamic Force Spectroscopy (DFS) we measure the small forces, in order of picoNewton, required to rupture single molecular bonds under gradually increasing loading. Important properties of specific molecular interaction, like unbinding forces, off-rates and binding energies can thereby be evaluated. We use force measuring optical tweezers which provides high-resolution force measurements on single cell level. We currently focus the research on characterization of the specific adhesion of the bacterial pathogen Helicobacter pylori.
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PI: Staffan Shedin
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