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Research groups at the Laboratory for Molecular Infection Medicine Sweden (MIMS)

MIMS Research Groups

arnberg niklas webVirus-host interactions

PI: Niklas Arnberg, Professor
Department of Clinical Microbiology, Division of Virology
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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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2011-02-22 sven bergstrm webPathogenesis, 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, This email address is being protected from spambots. You need JavaScript enabled to view it.

Group members:
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play Read more (Sven Bergström's web page at the Department of Molecular Biology)


Felipe CavaThe Cava Lab - The bacterial murein diversity

PI: Felipe Cava, Associate Professor
Department of Molecular Biology
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Before Felipe Cava joined MIMS,  he was group leader and assistant professor at the Universidad Autonóma de Madrid in Spain. From 2013 he is, after nomination by Umeå University, one of the first Wallenberg Academy Fellows, in the long-term programme for young researchers funded Knut and Wallenberg Foundation with SEK 7.5 Million during a five years period. Felipe Cava's research area is a very aggressive and original line focused on the diversity and plasticity of bacterial cell walls (primarily made of the murein exoskeleton) under environmental conditions, a topic of the highest relevance to properly understand bacterial relations with neighbouring organisms at all levels, from commensalism to pathogenesis.

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chabes andrei 2014dNTPs and maintenance of genome stability

PI: Andrei Chabes, Associate Professor
Department of Medical Biochemistry and Biophysics
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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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Emmanuelle Charpentier by HallhuberFioretti

Regulation in Infection Biology

PI: Emmanuelle Charpentier, Professor
Department of Molecular Biology


Our research relates to the field of Molecular Infection Biology. We are principally interested in understanding the molecular mechanisms governing physiology 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 in horizontal gene transfer, adaptation to stress, physiology or virulence. In particular, we do research on CRISPR, the adaptive immune system that protects bacteria against invading genetic elements; the small regulatory RNAs that interfere with bacterial pathogenicity; protein quality-control that regulates bacterial adaptation, physiology and virulence; and the mechanisms of bacterial recognition by immune cells.

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fallman maria mpn

Molecular mechanisms in the interplay between bacteria and host during gastrointestinal infections

PI. Maria Fällman, Professor
Department of Molecular Biology
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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.

playMaria Fällman's web page at the department of Molecular Biology



 

forsberg akeMolecular mechanisms of secretion of bacterial virulence effectors

PI: Åke Forsberg, Professor
Department of Molecular Biology
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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 II (T2SS), type III secretion system (T3SS) and Tat that 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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Nelson GekaraSignal transduction in host-microbial interactions and inflammation

PI: Nelson Gekara, Assistant Professor
Department of Molecular Biology
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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.


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vasili-hauryliuk 140Molecular mechanisms of the bacterial stringent response

PI: Vasili Hauryliuk, Associate Professor
Department of Molecular Biology
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Our research topic is the bacterial stringent response - an adaptation mechanism mediated by the alarmone nucleotide ppGpp, which exerts its regulatory role by attenuating the activity of numerous enzymes, with RNA polymerase being the main target. The intracellular levels of ppGpp are controlled by the RelA-SpoT Homologue (RSH) family of proteins, which either synthesize or hydrolyze ppGpp in response to various stress stimuli. Since the stringent response is implicated in regulation of bacterial virulence, antibiotic tolerance and biofilm formation, development of specific inhibitors of the stringent response is a promising strategy for the design of novel antimicrobials.

We are at the moment setting up a new lab at MIMS. Do you want to join us for a Master's project? Sent me an application to This email address is being protected from spambots. You need JavaScript enabled to view it.

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2010 johansson jrgen webRNA-mediated virulence regulation


PI: Jörgen Johansson, Professor
Department of Molecular Biology
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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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RichardMechanisms and dynamics of endocytic carrier formation during infection

PI: Richard Lundmark, Associate Professor
Department of Medical Biochemistry and Biophysics
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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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Andrea Puhar MIMS GLEndogenous danger signals in infection and inflammation

PI: Andrea Puhar
Department of Molecular Biology
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Our group studies the role of endogenous danger signals (DAMPs), in particular extracellular ATP (eATP), during intestinal infection and inflammation. We wish to understand how elements of the gut and the intestinal bacteria - both pathogens and commensals - regulate and respond to the dynamic appearance and disappearance of eATP and how this impacts on the development of disease.

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Overby_Anna_5426_110516_MPN_W2Tick borne encephalitis virus 

PI: Anna Överby, Assistant Professor
Department of Clinical Microbiology, Virology
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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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sjostedt andersType 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
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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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Constantin_Urban_5399_110516_MPN_W2Antifungal immunity

PI: Constantin Urban, Assistant Professor
Department of Clinical Microbiology
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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.

play Read more on the new webpage of the Urban group at the Department of Clinical Microbiology


Sun Nyunt WaiMolecular 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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Helicobacter pylori

 

Thomas BorenThomas Borén, Professor

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.

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play Read more (Thomas Borén's web page at Medical Biochemistry and Biophysics)

Bacteria-host interactions

 

Uhlin_Bernt_Eric_5460_110517_MPN_W2Bernt Eric Uhlin, Professor

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 ofgenes and gene products that contribute to the bacterial interactions with host environments.

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The Type III secretion system of pathogenic Yersinia

 

wolfwatz_hans_smallHans Wolf-Watz

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.

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Emmanuelle Charpentier about MIMS (2015):
“A sense of high-level education and high-level research, a respect for excellent research, an understanding of support for basic research, for long—term training of PhD students and understanding that good research also comes with time, good working conditions, a sense of community joining forces and reduced administrative burden, respect for junior scientists.” 

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