The emergence of oxygen on earth millions of years ago posed an existential threat to organisms and their constituent molecules that had evolved to survive under anaerobic conditions. “For systems optimized to function under such conditions, oxygen was actually toxic”, says first author and PhD student in the Martinez lab, Igor Asanovic. One such example is the ancient protein the scientist focused on in their study, tRNA ligase RTCB. This enzyme is essential for the maturation of tRNAs as well as for the splicing of an important messenger RNA, XBP1, which regulates the unfolded protein response. “Evolution took two routes to solve the problem. In plants and fungi, the protein was completely lost and replaced by another protein. But in animals, as we can now show, there was another solution”, says Igor Asanovic.
The scientists discovered that RTCB co-evolved with PYROXD1 as its sole antioxidative factor. “Most proteins rely on general cellular antioxidative systems”, says Igor Asanovic. “We can now show that this enzyme has a dedicated protector to shield it from inactivation through oxidation”. The researchers suggest that PYROXD1 employs a peculiar mechanism. The main molecule in cellular antioxidative defense is NAD(P)H, but NADP+ is a pro-oxidative factor. When the scientists reconstituted their system in vitro, PYROXD1 converted NAD(P)H to NADP+, which then had an antioxidant effect on RTCB. “How this actually works on an atomic level, however, is still mysterious”, says Igor Asanovic.
It remains to be seen whether the mechanism observed in the test tube operates in the same way in living cells and just how widespread the concept of dedicated protein-based antioxidants is. Studies, however, have implicated mutations in PYROXD1 in human disease and the scientists’ own data show that disease-associated variants of PYROXD1 fail to protect the tRNA ligase. “It was fascinating to me that it was not understood what such an essential protein like PYROXD1 actually does”, says Igor Asanovic. “Our work establishes the first mechanistic link between PYROXD1 and human myopathies. However, further work is required to better understand how, more precisely, the lack of oxidative protection is manifested in the disease state”, he concludes.
Igor Asanovic, Emilia Strandback, Alena Kroupova, Djurdja Pasajlic, Anton Meinhart, Pai Tsung-Pin, Nemanja Djokovic, Dorothea Anrather, Thomas Schuetz Marcin Józef Suskiewicz, Sirelin Sillamaa, Thomas Köcher, Rebecca Beveridge, Katarina Nikolic, Alexander Schleiffer, Martin Jinek, Markus Hartl, Tim Clausen, Josef Penninger, Peter Macheroux, Stefan Weitzer, Javier Martinez: The oxidoreductase PYROXD1 utilizes NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response. Molecular Cell 2021
https://doi.org/10.1016/j.molcel.2021.04.007
Monday Seminar (Internal)
Speaker: WU Shuangyang (Dolan), SCARAMUZZA Federico (Tessmar), KROGULL Daniel (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
The recently discovered ties between teeth and infants in human evolution
Speaker: Leslea HluskoInstitute: CENIEHHost: Nicole Grunstra
Characterisation of Vpr1, a novel protein involved in DSB repair
Speaker: Mustafa AlaaboInstitute: Dept. Chromosome Biology, Univ. ViennaHost: Franz Klein
Probing multi-scale dynamics in complex fluids and biological systems with differential dynamic microscopy
Speaker: Roberto CerbinoInstitute: University of ViennaHost: Arthur Sedivy
Marine symbioses fueled by wood
Speaker: Dan DistelInstitute: Ocean Genome Legacy CenterHost: Jillian Petersen
New insights in gene regulation and chromatin folding by enhancers and cohesin
Speaker: Wouter de LaatInstitute: Hubrecht InstituteHost: Christa Bücker
Molecular mechanism analysis involved in mitochondrial sheath formation and spermiation processes using gene-manipulated mice
Speaker: Keisuke ShimadaInstitute: Research Institute for Microbial Diseases, Osaka UniversityHost: Andrea Pauli
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Exploiting a unique post-translational modification to enhance subunit selection and activity of a tumor suppressor complex
Speaker: Derek TaylorInstitute: Departments of Pharmacology and Biochemistry,Case Western Reserve University, Cleveland OHIOHost: Thomas Leonard and Egon Ogris
From non-coding RNAs to non-canonical Mutations in Cancer
Speaker: Sven DiederichsInstitute: DKFZHost: Julius Brennecke
Chemical tools to study nucleic acids by biophysical methods
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Microbial trait-based scaling from single populations to communities with consequences for ecosystem processes
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How chromosome architecture shapes brain architecture
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Comprehensive and quantitative characterization of aneuploidy phenotypes
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Cellular crosstalk in Neurodevelopmental Disorders
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Top down and bottom up exploration of human gut microbial communities
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Title to be announced
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The Mirage of Biosocial Complexity: Critique and Collaboration Around the Tools of Epigenetics
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
Speaker: SHUNMUGAM Dhanlakshmi (Baccarini), CECI GINISTRELLI Lavinia (Mendjan), VORLÄNDER Matthias (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Title to be announced
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Title to be announced
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
Speaker: ATTRILL Sarah (Dolan), UIJTTEWAAL Esther (Elling), SCIBISZ Grzegorz (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Title to be announced
Speaker: Rotem SorekInstitute: Weizmann Institute of Science, RehovotHost: Julius Brennecke
Monday Seminar (Internal)
Speaker: KRUMWIEDE Luisa (Gaidt), KAPRAL Thomas (Zagrovic)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KOBAKHIDZE George (Dong), ANGELOPOULOU Eleni (Ellis), PACHANO Tomas (Stark)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Stephan GrillInstitute: MPI of Molecular Cell Biology and GeneticsHost: Clemens Plaschka
Monday Seminar (Internal)
Speaker: RAMIREZ America (Köhler), VÖLKL Isabella (Bücker), HOANG Oi Pui (Technau)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
Speaker: LEITNER Moritz (Martinez), VOGEL Alexander (Yudushkin), KETTEL Paulina (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
Speaker: TSAREV Aleksandr (Ameres), FIESELER Charlie (Zimmer), ABESAMIS Kim Ivan (Dong)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
Speaker: HEIDARI KHOEI Heidar (Rivron), KLEIFELD Justus (Urban), ORLIC Lucija (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: MIHAILOVIC Milica (Karagöz), BELL Lillie (Clausen), TELONI Federico (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: STANKUNAS Edvinas (Köhler), LEV Itamar (Zimmer)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: OBERHUEMER Michael (Leeb), GONAZLEZ ALVARADO Maria (Grade), SCHOLZ Julia (Otsuka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: AMANN Sascha (Haselbach), KASHKO Nataliia (Matos), BAUER Bernd (Martens)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: LEE Joonsun (Elling), LEYVA GONZALEZ Marco (Tanaka), MILIVOJEV Nadja (Raible)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: GAO Peng (Dagdas), GOGOVA Rebeca (Clausen), PAVLOVA Anzhela (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: AYALA MUNOZ Farja (Plaschka), VETRANO Pamela (Ramundo), YU Changwei (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KONSTANTINOU Andri (Obenauf), NAVA GARCIA Marintia (Dagdas), WOLFF Uyen Le Phuong (Jantsch V.)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: HARTMANN Felix (Matos), PASSERA Alessandro (Balzarotti), SANCHEZ BURGOS Laura (Obenauf)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: SILVA Raquel (Foisner), HODAKOVA Zuzana (Haselbach), MYLARSHCHIKOV Dmitry (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Johannes WalterInstitute: Harvard Medical SchoolHost: Jan-Michael Peters
Monday Seminar (Internal)
Speaker: PIECH Lucas (Leonard), DE LA CONCEPCION Juan Carlos (Dagdas), POPOVA Mariia (Peters)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: GALLI Lucrezia (Tanaka), DIAS Ana Beatriz (Slade), TAKACS Zsuzsanna (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KNIEST Judith (Haselbach), KELLNER Max (Penninger), BABADEI Olga (Decker)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: BOHAUMILITZKY Lena (Pinheiro), RAIDERS Stephan (Tanaka), PRLESI Ines (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: ZHAN Ni (Dagdas), PITASI Mattia (Leeb), HEINZL Monika (Stark)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: VELETI Lalitha (Pauli), ENGL Magdalena (Slade), NAAS Julia (Van Haeseler)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: FARAWAY Rupert (Plaschka), GRUNDMANN Lorenz (Haselbach), KLEINWAECHTER Ava (Slade)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: RÖTZER Johannes (Dolan), MIOCIC-STOSIC Fran (Zagrovic), RITSCHKA Birgit (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: PUSHPA BOSE Greeshma (Urban), RAINA Shiviya (Dammermann)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: SHARMA Sanskriti (Ellis), JANKOWSKA Julia (Ameres), PAPAREDDY Ranjith (Dagdas)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: MAURER Eric (Peters), BHARDWAJ Vishakha (Schlögelhofer), DIEZMA Laura (Nordborg/Mari-Ordonez)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: GUZMAN PEREZ Sebastian (Martinez), LITTLEBOY Jamie (Knoblich), RIABOV Daria (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: ZEILER Christina (Kovarik), DOCAVO GARCIA Antonio (Jachowicz), Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: ZMAJKOVIC Jakub (Zuber), DEL CHIARO Alessia (Dagdas), ANTONIOLI Sumire (Leonard)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: HUETTER Christiane (Menche), KRACHT Laura (Knoblich), SANDRU Ana Maria (Baccarini)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: BENEDUM Johannes (Slade), KALIS Robert (Zuber), PATEL Rajvi (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: PROTSENKO Liudmila (Brennecke), SHETTY Kavya (Hein), BASSAT Elad (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs