Signal transduction in host-microbial interactions and inflammation
PI: Nelson Gekara, PhD, Assistant Professor
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). PRRs include Toll-like receptors (TLRs), found on the cell surface or endosomal compartments and intracellular receptors such as NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) cytoplasmic DNA sensors. 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 meant to protect the host, excessive or deregulated induction of these innate immune responses, can either lead to self-injury (e.g. during sepsis or autoimmune diseases). Therefore, in order to maintain an optimal balance between anti-microbial host defenses and protection from self-harm, 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. In particular, we are interested in how DNA damage and the ubiquitin system modulate inflammatory responses.
In vivo mouse models of inflammation and infections (bacteria and viruses). In vitro studies using a variety of techniques including flow cytometry, microscopy, lentiviral transduction, mass spectrometry, cell culture, protein biochemistry, and cell/molecular biology techniques.
Our lab belongs to The Laboratory for Molecular Infection Medicine Sweden (MIMS). MIMS constitutes the Swedish node within the Nordic Partnership for Molecular Medicine that is formed together with the European Molecular Biology Laboratory (EMBL) and the Finnish (FIMM), Norwegian (NCMM) and Danish (DANDRITE) 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.
Selected relevant publications:
- Gekara, NO. DNA damage-induced immune response: Micronuclei provide key platform. Journal of Cell Biology 2017, August 31 216 (10). 2999-3001.
- Webster SJ, Brode S, Ellis L, Fitzmaurice TJ, Elder MJ, Gekara NO, Tourlomousis P, Bryant C, Clare S, Chee R, Gaston Hill JS, Goodall JC: Detection of a microbial metabolite by STING regulates inflammasome activation in response to Chlamydia trachomatis infection. PLoS Pathogens, 2017, June 1; 13 (6) artikel-id e1006383
- Erttmann SF, Härtlova A, Sloniecka M, Raffi FA, Hosseinzadeh A, Edgren T, Rofougaran R, Resch U, Fällman M, Ek T, Gekara NO. Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity. Immunity. 2016 Jul 19;45(1):106-18.
- Panda S, Nilsson JA and Gekara NO. Deubiquitinase MYSM1 regulates innate immunity through inactivation of TRAF3 and TRAF6 complexes. Immunity. 2015 Oct 13;43(4)
- Härtlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kröger A, Nilsson JA, Ek T, Weiss S, Gekara NO. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity. 2015 Feb 17;42(2):332-43.
- Dietrich N, Rohde M, Geffers R, Kroeger A, Hauser H, Weiss S and Gekara NO. Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria. Proc Natl Acad Sci U S A. 2010 May 11 Vol 107(19):8748-53.
- Gekara NO, Zietara N, Geffers R and Weiss S. L. monocytogenes induces T cell receptor unresponsiveness via its pore forming toxin Listeriolysin O. Journal of Infectious Diseases. Dec 2010. Vol 202(11):1698-707.
- Dietrich N, Lienenklaus S, Weiss S and Gekara NO. Murine Toll-Like Receptor 2 Activation Induces Type I Interferon Responses from Endolysosomal Compartments. PLoS One. April 2010. Vol 5 (4): e10250.
We welcome applications/inquiries from highly motivated scientists for a possible postdoctoral, doctoral, MSc or BSc training.
Swedish summary on the research of Nelson Gekara's group (www.umu.se)
Watch Nelson Gekara in the movie about Umeå University