Identifying and investigating the role of ribosome heterogeneity in pancreatic cancer

Title	Identifying and investigating the role of ribosome heterogeneity in pancreatic cancer
Acronym	DISCOVER
Start date	2022-07-01
End date	2025-06-30
Sponsor	Marie Skłodowska-Curie Action (MSCA)
Institution	University of Copenhagen

Associated cell lines

Project Description

The crucial complex of ribosomal RNAs (rRNA) and ribosomal proteins known as the ribosome is responsible for translating genetic material into proteins. Ribosomes were thought to be housekeeping structures incapable of differentiating between various mRNAs. However, recent research from the Lund lab and others revealed that ribosomes have distinct compositions and modifications both at the protein and rRNA modification level, leading to the creation of ribosome subtypes (ribosome heterogeneity). The idea that ribosome subtypes offer an extra level of regulation to precisely control gene expression was strongly reinforced by subsequent research from the Lund group. Ribosomes' functional specialization is still being studied, therefore there is still much to learn about their functions in many biological circumstances, diseases, and the specific mechanisms that underlie them. In this project, I will focus on translation in pancreatic cancer as one of the deadliest malignancies and a significant unresolved health issue. The main goal would be identifying ribosome heterogeneity and observing its effects on pancreatic ductal adenocarcinoma (PDAC) by focusing on alterations in rRNAs and ribosomal proteins. My hypothesis is that specialized ribosomes, with specific compositions and modifications at the protein and RNA levels, are positively chosen for translating mRNAs which promote pancreatic cancer. Based on the starting hypothesis, the expected observation is to detect significant effects of 2’-O-methylation of rRNAs and differential association of proteins to the core ribosome in pancreas tumorigenesis. These expected results would add to the knowledge of cancer- specific ribosomes in pancreatic cancer. This knowledge could be helpful for the development of new cancer prognostics and therapies.