The stage is yours, DIDO!
Paralogous proteins have evolved from gene or whole genome duplications and may provide an insurance policy for deleterious mutations. Why some paralogous proteins exist, however, remains somewhat enigmatic, as they consume substantial cellular energy resources despite often having homologous functions. In a new study published in Nature Communications, corresponding author Dea Slade, together with first author Johannes Benedum and their team, investigated the paralogous proteins PHD finger protein 3 (PHF3) and Death-inducer obliterator (DIDO). They found that the proteins collaboratively regulate gene expression and that, intriguingly, transcriptional upregulation of DIDO3 can compensate for the loss of PHF3. Collaborators are the Zagrovic lab and the Akalin lab at the Berlin Institute for Medical Systems Biology.
ERC Consolidator Grant for Shotaro Otsuka
Perutz group leader Shotaro Otsuka has received one of the most prestigious awards for researchers in Europe - the ERC Consolidator Grant. The total funding of €2 million over 5 years recognizes both Shotaro’s past achievements and future potential. The Otsuka lab is investigating the inter-organelle communication between the endoplasmic reticulum and the nucleus. The project “conNEctoER” aims to understand the structure and function of membrane connections that link the nucleus to the endoplasmic reticulum.
New Max Perutz PhD fellows
The Max Perutz PhD Fellowship honors the most ambitious and innovative PhD projects at the institute. This year’s awardees are Jeanne Fesselet (Kovarik lab) and Manuela Sophie Koller (Campbell lab). Their projects will investigate the role of mRNA decay in promoting plasticity of resident macrophages and the phenotypic effect of aneuploidy in yeast, respectively.
Egon Ogris appointed Professor of Medical Biochemistry
Congratulations to group leader Egon Ogris on being promoted to professor at the Medical University of Vienna.
Vienna BioCenter PhD award for Perutz alumnus Henry Thomas
Henry Thomas, formerly a PhD student in the Buecker lab, is among this year’s exceptional young scientists who have received the Vienna BioCenter PhD award. Henry is the 20th Max Perutz Labs student to receive the prize for their PhD work. In 2005, the prize was introduced by former Perutz group leader Renée Schroeder and acknowledges the best PhD theses across the four research institutes at the Vienna BioCenter. Among previous awardees are current Perutz group leaders Martin Leeb and Stefan Ameres.
Phosphatase loss spells problems for the prostate
Approximately one in eight men will be diagnosed with prostate cancer in his lifetime. Prostate cancer is commonly androgen addicted, in which case androgen receptor signal inhibitors (ARSI) can prolong survival. However, the cancer cells eventually develop resistance to ARSIs, resulting in poor clinical outcome. The molecular mechanisms underlying AR-mediated prostate cancer progression remain unclear. In a new study published in Nature Communications, co-corresponding author Egon Ogris and his team, together with collaborators from the University of Pennsylvania, the University of Michigan and the University Medical Center Hamburg-Eppendorf, show that leucine carboxy methyl transferase 1 (LCMT1) suppresses AR signaling and that its product, methylated protein phosphatase 2A (PP2A), is a valuable prognostic marker and potential therapeutic target.
Why TOFU is good for worms
Transposons are DNA sequences that can catalyze their own movement within and between genomes, and are a major source of species diversification. Uncontrolled, however, they are dangerous and can threaten the viability of an organism. In work just published in Nature, Max Perutz Labs group leader Sebastian Falk and his collaborator René Ketting (Institute of Molecular Biology, Mainz, Germany) describe the discovery of a new complex that regulates the activity of transposons in the nematode worm, C. elegans. The work exposes a potential molecular link between innate immune responses to invading pathogens and mechanisms that control transposable elements.
Goldilocks and the E3 ligase
Our innate immune system provides the first line of defense against invading pathogens. However, hyperactivation of these defenses can lead to inflammatory syndromes such as arthritis. Controlling the transcriptional programs that drive the innate immune response is therefore critical. In work recently published in eLife, the Versteeg lab has identified a factor essential for the degradation of the transcription factor IRF1, a key driver of the innate immune response. The work establishes a cellular mechanism by which cells maintain IRF1 levels in a so-called ‘Goldilocks zone’, thereby guarding against IRF1-driven inflammation.
Broadcasting DNA using transposons: ERC Starting Grant for Irma Querques
New group leader Irma Querques has received a Starting Grant from the European Research Council (ERC) to support her research project 'BROADCAST'. Irma and her team aim to better understand the mechanisms, functions and applications of transposons, bridging structural biology and biochemistry to biotechnology. The ERC Starting Grant is awarded to outstanding scientists starting their own independent research lab.
Network-based approaches open a new avenue to classify and treat rare diseases
Scientists at CeMM, the Max Perutz Labs, and St. Anna Children’s Cancer Research Institute have achieved a significant advancement in the research of rare immune system disorders. Through a network-based approach, they have reclassified approximately 200 rare diseases. Initial comparisons with clinical data already demonstrate how this can enhance the prediction of treatment efficacy. Moreover, the study reveals for the first time the strong similarities between the molecular mechanisms of rare diseases and autoimmune and autoinflammatory conditions, such as chronic inflammatory bowel disorders, multiple sclerosis, and specific types of diabetes. The study has now been published in Science Advances.
Prestigious fellowships awarded to Max Perutz Labs PhD students
Congratulations to Johannes Benedum, Elisabeth Holzer, and Alexandra Shulkina who have been awarded DOC Fellowships by the Austrian Academy of Sciences (ÖAW). Furthermore, congratulations to Anzhela Pavlova, who has received a BIF Fellowship from the Boehringer Ingelheim Fonds. Both programs offer funding for highly qualified doctoral candidates. This year’s fellowships support projects on DNA repair mechanisms, regulation of RNA polymerases, and mammalian autophagy.
Lipid Chemistry Empowers Nuclear Shape
The cell nucleus is surrounded by a spherical double membrane called the nuclear envelope. Scientists have long been intrigued by how this envelope can be elastic enough to accommodate shape changes that cells experience as they move through tissues, but also rigid enough to maintain nuclear integrity. A study by Anete Romanauska and Alwin Köhler, published in Nature Cell Biology, uncovers that the chemistry of membrane lipids is key for this versatility. When this chemistry is perturbed, the nuclear membranes become stiff and prone to rupture, and nuclei lose their typical round shape and morph into a polyhedron.