Elucidating the Role of Optineurin in Neuroprotection
Ivana Munitić (Laboratory of Molecular Immunology)
Andrea Markovinović, PhD student
Tamara Milojević, technician
Tereza Ljutić, mag.med.chem.
Vendi Šinkovec, undergraduate student
Department of Biotechnology, University of Rijeka
University of Rijeka collaborators:
Hrvoje Jakovac (Faculty of Medicine, University of Rijeka)
Kristina Grabušić (Department of Biotechnology, University of Rijeka)
Jonathan D. Ashwell (Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, USA)
Laura Ballerini (SISSA and University of Trieste, Italy)
Jean-Pierre Julien and Jasna Križ (Institut universitaire en santé mentale de Québec, Université Laval, Canada)
Damien Arnoult (INSERM, Villejuif, France)
Mutations in a widely expressed ubiquitin-binding protein optineurin were recently found in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease of unresolved pathogenesis. Unlike most of the other mutated proteins known to cause ALS by their toxic prion-like properties, optineurin is largely thought to cause disease by loss-of-function, arguing for its protective role. In vitro studies proposed that it regulates a variety of cellular processes including cell signaling, autophagy and vesicle trafficking, but their link to neurodegeneration is unknown. ALS is not an autonomous disease of selected neurons. Glial cells including microglia, are essential for neuroinflammation, which greatly influences disease progression. The major aim of this study is to elucidate the exact role(s) whereby optineurin exerts neuroprotection, pinpoint the cell types in which it acts, and determine its putative effect(s) on the interactions between the cell types relevant for neurodegeneration. Analyzing the function of optineurin in primary cells and mice models is crucial to the success of this study, given that ubiquitin-binding proteins are prone to in vitro artefacts. Incomplete understanding of ALS pathogenesis is directly mirrored in almost complete inability to treat ALS patients: a single approved drug exerts only a small prolongation in survival. Here, we propose to study a unique ALS model, set apart from the currently available models of direct toxicity by its ability to provide insight into basic neuroprotective mechanisms, thus expectedly paving the way for more successful therapies.
Markovinovic A, Cimbro R, Ljutic T, Kriz J, Rogelj B and Munitic I.
Optineurin in amyotrophic lateral sclerosis: multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms.
Progress in Neurobiology, in press (epub April 26, 2017).
Malatesti N, Munitic I, and Jurak I.
Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents.
Biophysical Reviews, 2017: 9(2), 149-168.
Pourcelot M, Zemirli N, Silva Da Costa L, Loyant R, Garcin D, Vitour D, Munitic I, Vazquez A, and Arnoult, D.
The Golgi apparatus acts as a platform for TBK1 activation after viral RNA sensing.
BMC Biology, 2016: 14, 69.
Meena NP, Zhu G, Mittelstadt PR, Giardino Torchia ML, Pourcelot M, Arnoult D, Ashwell JD and Munitic I.
The TBK1-binding domain of optineurin promotes type I interferon responses.
FEBS Letters, 2016: 590, 1498-1508.
Li CC*, Munitic, I*, Mittelstadt PR, Castro E and Ashwell, JD.
Suppression of dendritic cell-derived IL-12 by endogenous glucocorticoids is protective in LPS-induced sepsis.
PLOS Biology, 2015: 13, e1002269.
Munitic, I*, Giardino Torchia, ML, Meena NP, Zhu G, Li CC, and Ashwell, JD*.
Optineurin insufficiency impairs IRF3 but not NF-κB activation in immune cells.
Journal of Immunology, 2013: 191(12), 6231-40.
Open day 25.04.2017.
Department of biotechnology
University of Rijeka
On April 25, 2017 we had the honor to participate in the Open day of the Department of biotechnology. For this occasion, employees and students put an effort to show that science is interesting and fun, reaching out especially to our youngest members of the society. For this 5th edition of our Open day our laboratory tried to make it even more interesting, by preparing a play, which was performed by the students of our Immunology class.
Play: Who is stronger? The immune sistem or the viruses?
Whole video you can watch here :https://www.facebook.com/OdjelZaBiotehnologiju/videos/1531396680256413/
We are constantly in touch with bacterias and viruses, but fortunately only a few of them and not very often, manage to overcome our defences and cause a disease by making a big mess in our bodies. One of the major reasons why this happens only rarely is that the immune system acts as our shield. Indeed, our immune cells successfuly defend our organism from pathogens by powerfully attacking viruses, among others. Through our play we will show, in a simple way, how our immune system fights against viruses and how viruses fight back. In the process of attacking our body, some viruses manage to outsmart our immune system. We will show who is the winner in some of these fights, and why and how vaccines works in our favor in this fight.