We seek a motivated PhD student to join our research team to investigate  The role of MYC and p53 during Nucleolar Stress and ribosome biogenesis: a novel link to Cell Competition.

deadline June 17th 4:00PM; apply at https://www.unitn.it/en/ateneo/1961/announcement-of-selection

Project Description: The NOCs are a conserved family of nucleolar proteins that play a critical role in the control of protein synthesis necessary for the correct transport and assembly of the rRNA complexes and maturation of the ribosomal subunits ¹. We identify NOC1 as a novel MYC target essential for nucleolar homeostasis ² that plays a role in cell competition ³, a mechanism we characterized in Drosophila epithelial cells crucial for tissue homeostasis and organ size regulation ⁴, and relevant in tumorigenesis ⁵. We recently found that the reduction of NOC1 causes apoptosis and activates the DNA damage response with upregulation of p53 and nucleolar stress. This finding opens new avenues to identify which pathways link p53 in controlling cell competition to ribosomal stress. These studies will be extended to the role of human NOC1 in tumors and, with bioinformatic analysis, their correlation to tumors associated with ribosomepathies, genetic disorders caused by mutations in ribosomal proteins, and higher incidence of cancer, for which the mechanism is not yet clear.

Project Goals: Investigate the molecular mechanisms underlying NOC1-mediated cell competition. Explore the interplay between NOC1 and the DNA damage and p53 activation.

Determine the implications of NOCs family’s dysfunction in developmental abnormalities and cancer.

Methodologies: This project will use Drosophila and human cell systems (2ad 3D cultures) with a multidisciplinary approach, integrating molecular biology (RNA-seq, Ribo-seq, etc.) with live-cell imaging and bioinformatics analyses. The successful candidate will be able to work with cutting-edge technologies in a vivid and international environment https://www.cibio.unitn.it/.

If you are interested, please contact at paola.bellosta@unitn.it

https://pubmed.ncbi.nlm.nih.gov/?term=bellosta+p&sort=date&size=100

Paola Bellosta, Associate Professor of Genetics,

Department of Cellular, Computational, Integrative Biology CIBIO University of Trento, Italy.

https://www.cibio.unitn.it/657/laboratory-of-metabolism-of-cell-growth-and-neuronal-survival

https://twitter.com/BellostaLab

our lab is a member of the EU-Translacore COST action CA21154; see the program: https://translacore.eu/events

1.         Milkereit, P., Gadal, O., Podtelejnikov, A., Trumtel, S., Gas, N., Petfalski, E., Tollervey, D., Mann, M., Hurt, E., and Tschochner, H. (2001). Maturation and intranuclear transport of pre-ribosomes requires Noc proteins. Cell 105, 499-509. 

2.         Manara, V., Radoani, M., Belli, R., Peroni, D., Destefanis, F., Angheben, L., Tome, G., Tebaldi, T., and Bellosta, P. (2023). NOC1 is a direct MYC target, and its protein interactome dissects its activity in controlling nucleolar function. Front Cell Dev Biol 11, 1293420. 

3.         Destefanis, F., Manara, V., Santarelli, S., Zola, S., Brambilla, M., Viola, G., Maragno, P., Signoria, I., Viero, G., Pasini, M.E., Penzo, M., and Bellosta, P. (2022). Reduction of nucleolar NOC1 leads to the accumulation of pre-rRNAs and induces Xrp1, affecting growth and resulting in cell competition. J Cell Sci 135.

4.         de la Cova, C., Abril, M., Bellosta, P., Gallant, P., and Johnston, L.A. (2004). Drosophila myc regulates organ size by inducing cell competition. Cell 117, 107-116. 

5.         Esteban-Martinez, L., and Torres, M. (2021). Metabolic regulation of cell competition. Dev Biol 475, 30-36.