Cel "RNA editing is a type of programmed RNA sequence alteration that can result in a range of proteomic changes, from subtle fluctuations in output, to specific alterations in protein content. Editing is catalyzed by two classes of deaminases: those which convert adenosine to inosine (ADARs) and those which convert cytosine to uracil (APOBEC1). We have previously shown that APOBEC1-catalyzed editing in the transcriptome of macrophages leads to the generation of populations that are heterogeneous, and functionally diverse, enabling rapid population adaptation to different environmental settings. Our first aim for this proposal is to extend our studies to additional immune cell subsets, focusing on cells that are recently recognized as ""plastic"" to define the contribution of editing to this plasticity of fate and function.RNA editing of the type we study has also been demonstrated to be crucial for cancer progression. For instance, APOBEC1-deficiency significantly reduces tumour burden on cells of the intestine and colon that are prone to adenocarcinomas in the context of the APC-min mutation. This is also the case for testicular carcinomas in mouse models of such tumours. Thus, there is genetic evidence for a requirement for APOBEC1 and RNA editing to drive tumour progression, in two tumour contexts. Based on these data and on our recently deciphered role for APOBEC1 as a ""stealthy"" diversifier of cellular transcriptomes (and proteomic outcomes), we hypothesize that APOBEC1 drives tumour progression by editing select transcripts in tumour cells (or tumour stem cells), thus enabling the rapid adaptation of the tumour to the onslaught of the immune response. Our second aim is to characterize the subset of edited transcripts in these model tumours (either at the population or at the single cell level) and understand their role to tumour survival and progression, both in mouse models of disease, and in human tumour samples (in collaboration with QP Hammarstrom, KI)." Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicineimmunologymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsRNA Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-CoG-2014 - ERC Consolidator Grant Zaproszenie do składania wniosków ERC-2014-CoG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-COG - Consolidator Grant Instytucja przyjmująca DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Wkład UE netto € 1 839 172,50 Adres IM NEUENHEIMER FELD 280 69120 Heidelberg Niemcy Zobacz na mapie Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 839 172,50 Beneficjenci (3) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Niemcy Wkład UE netto € 1 839 172,50 Adres IM NEUENHEIMER FELD 280 69120 Heidelberg Zobacz na mapie Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 839 172,50 KAROLINSKA INSTITUTET Szwecja Wkład UE netto € 430 827,50 Adres Nobels Vag 5 17177 Stockholm Zobacz na mapie Region Östra Sverige Stockholm Stockholms län Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 430 827,50 THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Zakończenie uczestnictwa Zjednoczone Królestwo Wkład UE netto € 0,00 Adres TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Zobacz na mapie Region East of England East Anglia Cambridgeshire CC Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity Brak danych