Projects Offered
Petra Beli Mark Helm Ulrich Hohmann Edward Lemke Laura Lorenzo Orts Katja Luck Helle Ulrich Siyao Wang Johannes Mayer_DC3 Johannes Mayer_Interactome Wolfram RufEURECA - The European Epitranscriptomics of Cancer Academy
1 PhD project offered in the IPP winter call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
This PhD thesis project is integrated into the EURECA consortium. The overarching objective of EURECA - The European Epitranscriptomics of Cancer Academy-, is to train young doctoral candidates into excellence at the frontiers of basic and translational research by exploiting the cancer epitranscriptome to answer unmet clinical needs in cancer diagnosis, prognosis, and therapeutics and to drive change through knowledge and research. Epitranscriptomics is a new science field that studies RNA modifications (epitranscriptomic marks) and their function in regulation of gene expression. It is long known that many different RNA modifications exist. Yet, the true dimensions of the epitranscriptome were unveiled only in the last decade. It is now evident that RNA modifications affect the stability, function, subcellular localization and even immunogenicity of RNA to modulate essential cell programs like cell proliferation, differentiation, and stress response. Pathological changes in the epitranscriptome are seen as a new cancer hallmark: an independent mode of genetic reprogramming shaping cancer’s cell fate. We thus foresee that the epitranscriptome will prove to be a fundamental layer of gene regulation amenable to the clinics as a valuable tool in cancer diagnosis, prognosis and therapy.
PhD Project: Modulation of RNA modification in cancer by synthetic mRNA
The PhD student will develop mRNAs that augment then levels of certain RNA modification enzymes, to study gain-of-function effects. Using immune-silent modifications, we will develop mRNA formulations that do not “upset” the innate immune system, since immune reactions are particularly important when studying cancer. Application of these tools will allow spatio-temporal determination, if an increase of a given type of RNA modification is directly linked to the overexpression of a certain modification enzyme. This will also allow delineation of the borders of modification signatures of specific cancer cell lines. The project is planned with 3 internships of 2 months each in academic labs in Paris and Brussels, as well as in an enterprise in Vienna.
If you are interested in this project, please select Helm as your group preference in the IPP application platform.
Publications relevant to this project
Hertler J*, Slama K*, Schober B, Özrendeci Z, Marchand V, Motorin Y, Helm M* (2022) Synthesis of point-modified mRNA. Nucleic Acid Res, 50(20):e115 (*indicates joint contribution) Link
Bessler L, Vogt LM, Lander M, Dal Magro C, Keller P, Kühlborn J, Kampf CJ, Opatz T, Helm M (2023) A New Bacterial Adenosine-Derived Nucleoside as an Example of RNA Modification Damage. Angewandte Chemie (International ed. in English), 62(11):e202217128 Link
García-Vílchez R, Añazco-Guenkova AM, Dietman S, López J, Morón-Calvente V, D'Ambrosi S, Nombela P, Zamacola K, Mendizabal I, García-Longarte S, Zabala-Letona A, Astobiza I, Fernández S, Paniagua A, Miguel-López B, Marchand V, Alonso-López D, Merkel A, García-Tuñón I, Ugalde-Olano A, Loizaga-Iriarte A, Lacas-Viscasilla I, Unda M, Azkargota M, Elortza F, Bárcena L, Gonzalez-Lopez M, Aransay AM, Di Domenico T, Sánchez-Martín M, De Las Rivas J, Guil S, Motorin Y, Helm M, Pandolfi PP, Carracedo A, Blanco S (2023) METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer. Mol Cancer, 22(1):119 Link
