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TransGen RNA SIGNED

Transgenerational regulation of glucose metabolism by noncoding RNAs

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EC-Contrib. €

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 TransGen RNA project word cloud

Explore the words cloud of the TransGen RNA project. It provides you a very rough idea of what is the project "TransGen RNA" about.

regulation    sirna    kornfeld    environmental    builds    junk    lncrna    98    trace    obesity    entry    2nd    phenotyped    dynamic    regulate    reveal    organisms    et    15    proportion    dna    expectancy    untreated    energy    revealed    genomic    alters    profoundly    genome    reflect    vitro    unknown    annotated    intergenerational    mice    signaling    contrast    organ    paraphrased    glucoregulatory    rna    prediction    populations    disease    breedings    expression    t2d    mouse    tissue    poorly    gt    fertilization    paternal    hypothesize    life    dark    association    dysregulation    limited    seq    knockout    space    ask    gene    noncoding    algorithms    risk    proteins    ncrnas    encoding    implicated    legacy    serve    causally    hitherto    situated    lncrnas    shown    lab    homeostasis    mammals    transgenerational    metabolically    metabolism    1st    screening    gives    650    glucose    showing    lower    micrornas    germline    etiology    2013    inaptitude    models    insulin    interrogation    unpublished    generation    28    genetic    variants    functional    decline    pandemic    al    nature    generations    anti    liver    lamarckian    rnas   

Project "TransGen RNA" data sheet

The following table provides information about the project.

Coordinator
SYDDANSK UNIVERSITET 

Organization address
address: CAMPUSVEJ 55
city: ODENSE M
postcode: 5230
website: www.sdu.dk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Project website http://www.kornfeldlab.com
 Total cost 1˙344˙497 €
 EC max contribution 1˙344˙497 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2021-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    SYDDANSK UNIVERSITET DK (ODENSE M) coordinator 930˙637.00
2    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) participant 413˙860.00

Map

 Project objective

Obesity and T2D affect large populations and cause a decline in life expectancy if untreated. The pandemic proportion of obesity and inaptitude of anti-obesity approaches reflect our limited understanding of its complex environmental and genetic etiology. Genome-wide association studies revealed that disease-associated risk variants are often situated in those 98% of the genome not encoding for proteins. This noncoding genomic space yet does not reflect ‘Junk DNA’ but gives rise to >10,000 noncoding RNAs like microRNAs and long, noncoding RNAs (lncRNAs) that implicated in control of glucose metabolism and energy homeostasis also by the applicant (Kornfeld et al. Nature 2013).

LncRNAs were paraphrased as 'Dark matter of the genome' due to their tissue-specific and dynamic expression that contrast their poorly understood role in gene regulation. In the 1st part of this proposal, we ask if lncRNAs regulate glucose metabolism and are involved in the obesity-associated dysregulation of insulin signaling in the liver, the major glucoregulatory organ in mammals. Using RNA-Seq and novel lncRNA prediction algorithms, we observed that obesity alters expression of 28 annotated and 15 hitherto unknown lncRNAs in two mouse models of obesity. To identify lncRNAs causally controlling glucose metabolism, we established a siRNA screening system that allows functional interrogation of >650 lncRNAs. These in vitro findings serve as entry for the generation of lncRNA knockout mice that are metabolically phenotyped. In the 2nd part, we hypothesize that germline ncRNAs could control the transgenerational consequences of paternal obesity as shown for lower organisms. This builds upon unpublished findings from our lab showing that obesity profoundly changes expression of germline ncRNAs. In-vitro fertilization and intergenerational breedings will trace the legacy of paternal obesity across generations and reveal ncRNAs involved in this ‘Lamarckian’ control of glucose metabolism.

 Publications

year authors and title journal last update
List of publications.
2020 Marta Pradas-Juni, Nils R. Hansmeier, Jenny C. Link, Elena Schmidt, Bjørk Ditlev Larsen, Paul Klemm, Nicola Meola, Hande Topel, Rute Loureiro, Ines Dhaouadi, Christoph A. Kiefer, Robin Schwarzer, Sajjad Khani, Matteo Oliverio, Motoharu Awazawa, Peter Frommolt, Joerg Heeren, Ludger Scheja, Markus Heine, Christoph Dieterich, Hildegard Büning, Ling Yang, Haiming Cao, Dario F. De Jesus, Rohit N. Kul
A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-020-14323-y
Nature Communications 11/1 2020-02-06
2017 Motoharu Awazawa, Paula Gabel, Eva Tsaousidou, Hendrik Nolte, Marcus Krüger, Joel Schmitz, P Justus Ackermann, Claus Brandt, Janine Altmüller, Susanne Motameny, F Thomas Wunderlich, Jan-Wilhelm Kornfeld, Matthias Blüher, Jens C Brüning
A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle
published pages: 1466-1473, ISSN: 1078-8956, DOI: 10.1038/nm.4420
Nature Medicine 23/12 2019-07-08
2016 Elena Schmidt, Jan-Wilhelm Kornfeld
Decoding Lamarck—transgenerational control of metabolism by noncoding RNAs
published pages: 959-969, ISSN: 0031-6768, DOI: 10.1007/s00424-016-1807-8
Pflügers Archiv - European Journal of Physiology 468/6 2019-07-08
2016 Delphine Duteil, Milica Tosic, Franziska Lausecker, Hatice Z. Nenseth, Judith M. Müller, Sylvia Urban, Dominica Willmann, Kerstin Petroll, Nadia Messaddeq, Laura Arrigoni, Thomas Manke, Jan-Wilhelm Kornfeld, Jens C. Brüning, Vyacheslav Zagoriy, Michael Meret, Jörn Dengjel, Toufike Kanouni, Roland Schüle
Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue
published pages: 1008-1021, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.09.053
Cell Reports 17/4 2019-07-08
2018 Elena Schmidt, Ines Dhaouadi, Isabella Gaziano, Matteo Oliverio, Paul Klemm, Motoharu Awazawa, Gerfried Mitterer, Eduardo Fernandez-Rebollo, Marta Pradas-Juni, Wolfgang Wagner, Philipp Hammerschmidt, Rute Loureiro, Christoph Kiefer, Nils R. Hansmeier, Sajjad Khani, Matteo Bergami, Markus Heine, Evgenia Ntini, Peter Frommolt, Peter Zentis, Ulf Andersson Ørom, Jörg Heeren, Matthias Blüher, Martin Bilban, Jan-Wilhelm Kornfeld
LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05933-8
Nature Communications 9/1 2019-05-10
2019 Nils R. Hansmeier, Pia J. M. Widdershooven, Sajjad Khani, Jan-Wilhelm Kornfeld
Rapid Generation of Long Noncoding RNA Knockout Mice Using CRISPR/Cas9 Technology
published pages: 12, ISSN: 2311-553X, DOI: 10.3390/ncrna5010012
Non-Coding RNA 5/1 2019-03-12
2019 Paul Klemm, Peter Frommolt, Jan-Wilhelm Kornfeld
s ·nr: a visual analytics framework for contextual analyses of private and public RNA-seq data
published pages: , ISSN: 1471-2164, DOI: 10.1186/s12864-018-5396-0
BMC Genomics 20/1 2019-03-12

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