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UNEXPECTED ROLE OF PROTEIN RAF1 DISCOVERED IN LIVER CANCER
The most common type of liver cancer, called hepatocellular carcinoma (short: HCC), is one of the most prevalent tumours worldwide. The survival rate of patients with HCC is, to date, very poor.
This is in part due to the heterogeneity of the disease, as HCC tumours can exhibit very different molecular features, posing a problem for the development of targeted therapies.
The identification of each individual piece in this molecular puzzle is therefore absolutely vital to shed light on the entire picture of HCC, and will hopefully contribute to improve therapies in the future.
The protein RAF1 is a known player in many forms of tumours. In lung and skin, for example, RAF1 significantly contributes to tumour development. However, the most recent findings of Manuela Baccarini and her group, published in the journal Nature Communications, now uncover a very different role of RAF1 in HCC.
The researchers unravel novel roles of RAF1 in HCC, with opposite functions in different cell types within the liver. RAF1 puts the breaks on the proliferation of malignant hepatocytes, the actual tumor cells; therefore, and unexpectedly, RAF1 is a negative regulator of HCC. On the other hand, in inflammatory cells, RAF1 is required to create an environment which stimulates HCC growth. Read more |
NEW INSIGHTS IN VACCINIA VIRUS
Vaccinia virus, the viral vaccine used to eradicate smallpox, is a known model organism in the field of virology. It is frequently used to study viral interactions with the host immune system.
However, surprises are still in store for this well-studied organism. By employing structural biology approaches, Tim Skern and his group shed light on the structure of one of the vaccinia proteins responsible for the interaction with the host immune system, and encountered unexpected findings. The results are published in the journal Plos Pathogens.
The researchers were able to elucidate the entire protein structure of the protein A46. Surprisingly, an unusual lipid binding fold was found in the protein’s N-terminal domain. A further unexpected discovery is the fact that A46 is able to interact both with proteins as well as lipids, a rare occurrence. This indicates that A46 can use a variety of interactions to impair the immune response of a host cell.
The results were made possible through a global integrative effort together with former Max Perutz Postdoc Lynn Ten Eyck, Isabel Usón, who developed an innovative method to solve protein structures, and Kristina Djinović-Carugo.
A complete understanding of vaccinia virus is necessary as in the future, the virus could be applied in targeted tumour therapies as an oncolytic virus. Such viruses preferentially infect and kill cancer cells.
Publication in Plos Pathogens:
Fedosyuk S, Bezerra GA, Radakovics K, Smith TK, Sammito M, Bobik N, Round A, Ten Eyck LF, Djinović-Carugo K, Usón I, Skern T. Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins. PLoS Pathog. 2016 Dec 14;12(12):e1006079.
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A NEW PAPER BY MFPL ALUMNI IN COLLABORATION WITH BURNETT SCHOOL OF BIOMEDICAL SCIENCES, UNIVERSITY OF CENTRAL FLORIDA
Borrelia burgdorferi, a member of the phylum Spirochaetes, is the vector-borne bacterial cause for Lyme disease. It circulates between an arthropod vector (Ixodes ticks) and small vertebrate hosts, such as the white-footed mouse Peromyscus leucopus. Via the bite of an infected tick, B. burgdorferi is transmitted to humans. To ensure survival and pathogenesis, B. burgdorferi needs to adapt its gene regulation to the distinct host environments it encounters during its life cycle. A recent paper published in Nucleic Acids Research sheds light on the mechanisms underlying Borrelia’s adaptation of its transcriptome to a mammalian host. The work is the result of the collaboration of Philip Adams and Mollie Jewett from the Burnett School of Biomedical Sciences at the University of Central Florida with Renée Schroeder’s lab. Philip was a visiting PhD student at MFPL in 2014.
Publication in Nucleic Acids Research: Adams PP, Flores Avile C, Popitsch N, Bilusic I, Schroeder R, Lybecker M, Jewett MW. In vivo expression technology and 5’ end mapping of the Borrelia burgdorferi transcriptome identify novel RNAs expressed during mammalian infection. Nucleic Acids Research. 2016 Dec. 1. doi:10.1093/nar/gkw1180
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MFPL XMAS PARTY 2016
The MFPL held its Xmas Party on December 6th. The festivities included a "Cards against Humanity - MFPL Edition" game organised by Lucy Sneezum to raise money for the Stiftung Kindertraum charity.
As every year, members of the MFPL Faculty helped serve dinner. On this note, we would like to thank Egon Ogris, Javier Martinez, Martin Leeb, Thomas Decker and Fritz Propst.
So far, we have raised € 1.044,81 for Stiftung Kindertraum through the game - if you still wish to donate, you can do so by contacting Marion Linger on the 6th floor.
A big thank you to the organising team and helping hands, and to everyone attending for making it a great night!
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VBC CHRISTMAS PLAY 2016
For this year's Christmas play, the VBC Amateur Dramatic Club took the campus audience down the rabbit hole. In Alice's Experiments in Wonderland, we followed Alice on her quest to finish her PhD. As in every play, many well known VBC members were portrayed - maybe you even recognised yourself? Certainly, the play convinced us of one thing: We are all mad here!
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We are pleased to welcome David Romero, who started his PostDoc in Udo Bläsi’s lab!
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MFPL PUBLICATIONS
A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis.
Jeric I, Maurer G, Cavallo AL, Raguz J, Desideri E, Tarkowski B, Parrini M, Fischer I, Zatloukal K, Baccarini M.
Nat Commun. 2016 Dec 21
Cross-regulation by CrcZ RNA controls anoxic biofilm formation in Pseudomonas aeruginosa.
Pusic P, Tata M, Wolfinger MT, Sonnleitner E, Häussler S, Bläsi U.
Sci Rep. 2016 Dec 21
Phospholipids in Autophagosome Formation and Fusion.
Martens S, Nakamura S, Yoshimori T.
J Mol Biol. 2016 Oct 27.
UNC-84: "LINC-ing" chromosome movement and double strand break repair.
Silva N, Jantsch V.
J Cell Biol. 2016 Dec 13.
Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins.
Fedosyuk S, Bezerra GA, Radakovics K, Smith TK, Sammito M, Bobik N, Round A, Ten Eyck LF, Djinović-Carugo K, Usón I, Skern T.
PLoS Pathog. 2016 Dec 14;12(12):e1006079.
The Influence of Programmed Cell Death in Myeloid Cells on Host Resilience to Infection with Legionella pneumophila or Streptococcus pyogenes.
Gamradt P, Xu Y, Gratz N, Duncan K, Kobzik L, Högler S, Kovarik P, Decker T, Jamieson AM.
PLoS Pathog. 2016 Dec 14.
Human cytomegalovirus phosphoproteins are hypophosphorylated and intrinsically disordered.
Rieder FJ, Kastner MT, Hartl M, Puchinger MG, Schneider M, Majdic O, Britt WJ, Djinović-Carugo K, Steininger C.
J Gen Virol. 2016 Dec 13.
A Stress-Induced Bias in the Reading of the Genetic Code in Escherichia coli.
Oron-Gottesman A, Sauert M, Moll I, Engelberg-Kulka H.
MBio. 2016 Nov 15.
The Paralogous Histone Deacetylases Rpd3 and Rpd31 Play Opposing Roles in Regulating the White-Opaque Switch in the Fungal Pathogen Candida albicans.
Xie J, Jenull S, Tscherner M, Kuchler K.
MBio. 2016 Nov 15.
Calcium-dependent binding of Myc to calmodulin.
Raffeiner P, Schraffl A, Schwarz T, Röck R, Ledolter K, Hartl M, Konrat R, Stefan E, Bister K.
Oncotarget. 2016 Dec 1.
Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water.
Kurzbach D, Canet E, Flamm AG, Jhajharia A, Weber EM, Konrat R, Bodenhausen G.
Angew Chem Int Ed Engl. 2016 Dec 5.
In vivo expression technology and 5' end mapping of the Borrelia burgdorferi transcriptome identify novel RNAs expressed during mammalian infection.
Adams PP, Flores Avile C, Popitsch N, Bilusic I, Schroeder R, Lybecker M, Jewett MW.
Nucleic Acids Res. 2016 Dec 1.
Publications for the MFPL newsletter are collected from PubMed on a monthly basis. However, to ensure that your publication(s) is/are entered into the MFPL publication database and appear on the MFPL website, notify publications@mfpl.ac.at with the following information: PubMed ID (or alternatively all authors, title, journal), information on MFPL authors, and type of publication.
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MFPL ALUMNI
MARKUS KUBICEK
I studied Molecular Genetics at the University of Vienna, and joined the lab of Rainer Prohaska for my diploma thesis, where I got a profound training in protein biochemistry. For my PhD thesis, I joined the laboratory of Manuela Baccarini at the MFPL where I gained extensive experience in cell signaling. Later I was able to combine my excitement for both protein chemistry and cell signaling during a Marie-Curie funded post-doctoral stay in the laboratory of Vicente Andres at the CSIC in Valencia, Spain. Here I also started applying proteomic techniques to cardiovascular research.
Fascinated by the concept of studying not only single molecules but to assess the state of potentially all proteins in a particular pathologic situation, I happily accepted the offer to run my own proteomics research group at the Department of Laboratory Medicine at the Medical University of Vienna.
My academic career came to an end in 2010 when I joined the Austrian Science Fund (FWF) as a scientific project officer in the fields of biomedical research. It was not an easy decision to leave the bench, but to me it was the right move. I like the saying “once a scientist, always a scientist” and am glad that I continue to be so tightly connected to academic research. I can help move the horizons of scientific knowledge by facilitating funding decisions for highly competitive projects.
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THE MFPL PHD SELECTION 2017 IS NOW OPEN!
Interested in a PhD in Molecular Life Sciences at MFPL?
The PhD Selection Summer Call is now open until March 5th, 2017. For requirements, recruiting groups and more information please visit the "How to apply" section on the MFPL Homepage.
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MOVEMBER 2016
Did you ever wonder why some male VBC members grow moustaches in November? The reason is simple – it’s Movember! 15 members of the VBC joined the MoVBC team to collect donations for the Movember foundation, which seeks to make a contribution to men’s health by raising awareness for prostate and testicular cancer. In total, 781€ were raised! The campus also celebrated Movember at the Happy Hour with the theme „Wild Wild West“. A big thank you goes to Thomas Dechat and the whole team for their efforts!
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Well done to Gönül Kizilsavas (group Konrat) who defended her PhD thesis on "The chemistry of the oncogenic transcription factor Myc”. We also congratulate Andrea Flamm (group Konrat) who defended her PhD thesis "NMR spectroscopy of intrinsically disordered protein complexes" and Swastika Sanyal (group Gregan) to her PhD thesis entitled "Characterization of novel regulators of meiotic chromosome segregation in fission yeast, Schizosaccharomyces pombe".
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From January 13th to 16th, you can satisfy your need for caffeine at the Vienna Coffee Festival at Ottakringer Brauerei. Tickets are available online.
The Vienna Science Ball on January 28th is a great opportunity for your first waltz in 2017. The ball will take place in Vienna's town hall. Tickets are available online or via e-mail: karten@wissenschaftsball.at.
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09/07/2017, 11:00-12:00
Impromptu Seminar
Exposure of phosphatidylserine in apoptotic cells
Shigekazu Nagata
IMBA/GMI Lecture Hall
13/01/2017, 09:00-10:00
RNA Lecture Series
The journey of mRNA: from chromatin to the nuclear pore complex
Catherine Dargemont
IMBA/GMI Lecture Hall
13/01/2017, 11:00-12:00
RNA Lecture Series
Enhancer clusters in early embryonic development
Christa Bücker
IMBA/GMI Lecture Hall
13/01/2017, 16:00-17:00
Current Topics at VBC
Epigreenetics
Ortrun Mittelsten Scheid
IMP Lecture Hall
16/01/2017, 09:30-10:30
MFPL Impromptu Seminar
Serotonin and dopamine signaling regulates diapause in Drosophila
Gabriele Andreatta
Seminar room 4.120, MFPL (4th floor)
16/01/2017, 11:00-12:00
Impromptu Seminar
Characterisation of mice deficient for the pro-survival BCL-2 family member A1
Robyn Schenk
IMP Seminar room 1
20/01/2017, 09:00-10:00
RNA Lecture Series
Regulatory Protein-RNA Interactions
Markus Landthaler
IMBA/GMI Lecture Hall
20/01/2017, 11:00-12:00
RNA Lecture Series
Knocking out circRNAs and reconstructing tissues from single-cell sequencing
Nikolaus Rajewsky
IMBA/GMI Lecture Hall
26/01/2017, 11:00-12:00
SFB Chromosome Dynamics SEMINAR TALK
Genome in 3D: models of chromosome folding
Leonid Mirny
IMP Lecture Hall
27/01/2017, 09:00-10:00
RNA Lecture Series
Origins of Life Systems Chemistry
John Sutherland
IMBA/GMI Lecture Hall
27/01/2017, 11:00-12:00
RNA Lecture Series
Title to be announced
Lee Cronin
IMBA/GMI Lecture Hall
27/01/2017, 11:00-12:00
VBC Regular Seminar
Rapid evolution of the cancer karyotype
David Pellman
IMBA/GMI Lecture Hall
For further meetings and events check the EMBO meetings, Nature’s events directory and Cell Symposia websites!
Policies, guidelines, templates, and information material (annual reports, logo files, living in Vienna etc.) can be found on the infoshare of the MFPL Intranet.
Please inform the communications team of your upcoming publications and news by e-mail to communications@mfpl.ac.at
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