 Virus-host interactions
PI: Niklas Arnberg, Professor
Department of Clinical Microbiology, Division of Virology
Contact: niklas.arnberg climi.umu.se
In our project we are identifying and characterizing molecules and molecular mechanisms that regulate virus binding to host cells.
We focus on adenoviruses, picornaviruses and to some extent influenza A virus. A major goal of our research is to define target mechanisms for antiviral treatment.
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 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.
Contact:
Sven Bergström
Group members:
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 dNTPs and maintenance of genome stability
PI: Andrei Chabes, Associate Professor
Department of Medical Biochemistry and Biophysics
Contact:
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The four dNTPs (dATP, dTTP, dCTP and dGTP) are the building blocks of DNA. A balanced supply and a correct overall concentration of dNTPs are key prerequisites for faithful genome duplication. Therefore, production of dNTPs is tightly regulated by multiple mechanisms. The concentration of dNTPs fluctuates during the cell cycle.
We are investigating (i) how the DNA damage checkpoint, a genome surveillance mechanism, regulates the concentration of dNTPs, and how dNTPs regulate the activation of the DNA damage checkpoint and (ii) how the imbalanced dNTP pools affect the fidelity of replication and how different replication errors are recognized and repaired.
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 Molecular mechanisms governing Gram-positive bacterial pathogenesis
PI: Emmanuelle Charpentier, Associate Professor
Department of Molecular Biology
Contact:
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Our research relates to the field of Molecular Infection Biology. We are overall interested in understanding the molecular mechanisms governing physiology-, virulence- and infection-associated processes in Gram-positive bacterial pathogens. We use a combination of genetic, genomic, molecular, biochemical, physiological and cell infection approaches to study mechanisms of gene expression at the transcriptional and post-transcriptional level that control horizontal gene transfer, adaptation to stress, physiology or virulence. We particularly research on CRISPR, the recently discovered adaptive immune system that protect bacteria and archaea against invading genetic elements; the small regulatory RNAs that interfere with bacterial pathogenicity; protein quality control that regulate bacterial adaptation, physiology and virulence; and the mechanisms of bacterial recognition by immune cells.
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 Molecular mechanisms in the interplay between bacteria and host during gastrointestinal infections
PI. Maria Fällman, Professor
Department of Molecular Biology
Contact:
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Maria Fällman and her research group study mechanisms in bacterial gastrointestinal infections, both from the view of bacteria and host. She has made groundbreaking discoveries concerning molecular mechanisms behind Yersinia resistance to phagocytosis where she identified and characterized the host cell target proteins for the virulence effector YopH.
The lab was behind the finding that sub-lethal doses of Yersinia result in persistent infection in mice. Current work related to this involve studies of bacterial adaption and role of immune defence mechanisms using transcriptomic and proteomic analyses. Other projects involve metabolomics as potential practical applications in diagnosis and antibiotic resistance determinations.
The group is involved in studies of effector translocation by the Type Three Secretion System (T3SS) where they together with the Wolf-Watz lab demonstrated the alternative mechanism för T3SS delivery from the bacterial surface. The Fällman group focuses on the instant action of the virulence effectors on immune cells and they recently showed the mechansm by which the effector YopK directs T3SS delivery, required for a productive infection. They have also shown that macrophages and dendritic cells are differently affected by antiphagocytic virulence effectors and that it relay on the host cell recognition mechanism.
Maria Fällman's web page at the department of Molecular Biology
 Molecular mechanism of T3SS mediated targeting of virulence effectors
PI: Åke Forsberg, Professor
Department of Molecular Biology
Contact:
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Åke Forsberg is a Professor at the Department of Molecular Biology and is the scientific secretary of UCMR/MIMS and the director of the UCMR research school. The research interests of his group are the secretion systems important for virulence of Yersinia and Pseudomonas. The basic research is focusing on the molecular mechanisms of two protein secretion systems, type III secretion system (T3SS) and Tat that both are critical for virulence.
In collaboration with LCBU and the Department of Chemistry his research group has set up a screening assay for identification of small molecules that block Tat function and in Yersinia and Pseudomonas, these molecules will be validated for antimicrobial activity in different infection models.
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 Signal transduction in host-microbial interactions and inflammation
PI: Nelson Gekara, Assistant Professor
Department of Molecular Biology
Contact:
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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.
My group is just starting at MIMS. Highliy motivated postdocs and PhD students are welcome to contact me.
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 RNA-mediated virulence regulation
PI: Jörgen Johansson, Professor
Department of Molecular Biology
Contact:
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The intracellular pathogen Listeria monocytogenes has turned out to be a very important model for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts.
We are studying different aspects of RNA-mediated virulence gene regulation in L. monocytogenes.
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 Mechanisms and dynamics of endocytic carrier formation during infection
PI: Richard Lundmark, Associate Professor
Department of Medical Biochemistry and Biophysics
Contact:
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Our research aims to characterise proteins and general themes involved in endocytosis, focusing on identifying mechanisms behind initiation, generation and termination of endocytic carrier formation. The project takes a novel approach on infection through studies on how bacteria and viruses exploit membrane-remodelling machineries in the target cell to facilitate cell entry. We use our established molecular tools to study the internalisation of pathogens by visualising the dynamics and specificity of carrier formation using advanced four-dimensional fluorescent microscopy. The aim is to identify general principles for how extracellular agents like bacterial toxins can transmit activating signals to the intracellular endocytic protein networks and understand how this mechanistically leads to the creation of membrane vehicles.
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 Tick borne encephalitis virus
PI: Anna Överby, Assistant Professor
Department of Clinical Microbiology, Virology
Contact:
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Tick borne encephalitis virus (TBEV) is an important emerging human pathogen. My group focuses on studying the interactions between the virus and the innate immune system, and determining pathogenicity factors of TBEV. Anna Överby has started her laboratory at MIMS in January 2011, and is in the process of recruiting PhD students and Post docs.
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 Type VI secretion systems of Gram-negative bacteria - defining the functions of T6SS components and their contribution to virulence
PI: Anders Sjöstedt, Professor
Department of Clinical Microbiology
Contact:
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There are six specialized secretion systems in Gram-negative bacteria. The Type VI secretion systems (T6SSs), identified in almost 100 different bacterial species, are essential for virulence of many important human pathogens such as Vibrio cholera and Pseudomonas aeruginosa. Still, the understanding of T6SSs in general is very incomplete. The overall aim of our work is to delineate the regulation and functions of effector proteins of T6SS, primarily Francisella tularensis, but also Vibrio cholera will be studied. We will utilize molecular techniques to generate specific mutants as well as tagged T6SS components. Their subsequent localization and secretion during infection will then be detected by a variety of techniques, including direct microinjection of bacteria or T6SS components into host cells. We are also studying the possibility to inhibit the functions of T6SS by means of small molecular inhibitors.
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 Antifungal immunity
PI: Constantin Urban, Assistant Professor
Department of Clinical Microbiology
Contact:
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Opportunistic fungal mycoses caused by Candida albicans or Aspergillus fumigatus for instance, have evolved into major human diseases in the past decades. My group is interested in the fundamental processes of host-pathogen interaction during these infections. We therefore study the molecular mechansims of the innate immune system to contain mycoses as well as the strategies Candida and Aspergillus employ to evade the attack of the host. One of our majors goals is to apply this knowledge for the development of novel antifungal therapies.
To unravel the described mechanisms the lab uses diverse approaches and methodologies ranging from molecular genetics, transcriptomics (RNA-Seq), chemical biology screening to X-ray nano-chemical imaging or ICP masspectrometry..
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 Molecular mechanisms of bacterial pathogenesis
PI: Sun Nyunt Wai MD, PhD
Professor of Medical Microbial Pathogenesis
Department of Molecular Biology
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Our main goal is to understand the mechanisms used by pathogenic bacteria in their interaction within a host and for their survival in different environments contributing to the intestinal and extra-intestinal pathogenesis, environmental survival and emergence of new pathotypes. We study the Vibrio cholerae because it is a major pathogen responsible for the life-threatening acute diarrhoea, cholera, which is a worldwide problem. V. cholerae is not only an important bacterial pathogen but it also serves as a model system for studies of many important aspects of medical microbial pathogenesis, e.g. how bacteria regulate and express virulence factors, cause damage in the host, and adapt to different environmental conditions are thereby important issues. Using new approaches we have shown how the bacteria may modulate expression of virulence and how the bacteria transport virulence factors via membrane vesicles. We have identified factors and possible mechanisms contributing to both environmental persistence and to their balanced interaction with the human host.
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Research Groups
