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Signal transduction in host-microbial interactions and inflammation
PI: Nelson Gekara, Assistant Professor
My group is just starting at MIMS. Highliy motivated postdocs and PhD students are welcome to contact me.
Department of Molecular Biology
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.
Background: 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). PRRs detect highly conserved molecular structures on microbes called microbial associated molecular patterns (MAMPs). PRRs also detect molecular structures released by stressed or damaged host cells.These endogenous molecules are generally referred to as damage-associated molecular patterns (DAMPs).
PRRs are broadly categorized into three classes: Toll-like receptors (TLRs), found on the cell surface or endosomal compartments and NOD-like receptors (NLRs) and RIG-I-likereceptors (RLRs) located in the cytoplasm. Activation of PRRs results in the production of a large set of proinflammatory cytokines and type I interferons (IFNs) which act concertedly to coordinate host defenses against foreign invasion. Although principally meant to protect the host, excessive or deregulated induction of such innate immune responses, can either lead to self injury (e.g during sepsis or autoimmune diseases) or the impairment of some immune defenses hence susceptibility to certain infections. Therefore in orders to maintain an optimal balance between anti-microbial host defenses and guarding against causing self injury, PRR signaling pathways must be regulated tightly.
We are interested in understanding the mechanisms that govern the regulation of PRRs signaling pathways and how the breakdown of such regulation may lead to inflammation or impair anti-microbial host defenses.
Dietrich N, et al, Proc Natl Acad Sci U S A. 2010 May 1;107(19):8748-53;
Dietrich et al. PLoS One. 2010 Apr 20;5(4).
These studies will involve using various in vivo mouse models of inflammation andinfection as well in vitro studies using a variety of techniques including flow cytometry,microscopy, lentiviral transduction, mass spectrometry, standard cell culture, proteinbiochemistry, and cell/molecular biology techniques.
Our new lab in Sweden belongs to the MIMS (The Laboratory for Molecular Infection Medicine Sweden (MIMS) within the Nordic EMBL Partnership for Molecular Medicine). MIMS constitutes the Swedish node within the Nordic partnership for Molecular Medicine thatis formed together with the European Molecular Biology Laboratory (EMBL) and the Finland and Norway nodes. MIMS is established within the Umeå Centre for Microbial Research (UCMR) at Umeå University. The groups of the MIMS work in modern laboratories with well equipped common facilities and platforms in a creative, inspiring and highly interactive environment.
Swedish summary on the research of Nelson Gekara's group (www.umu.se)
Watch Nelson Gekara in the movie about Umeå University