WP 6.3
Test-cases and identification of novel therapeutic RNA molecules

General objectives

  1. Identify new therapeutic ncRNAs impacting translation/epi-transcriptome and develop miRNA restoration approaches
  2. Develop new strategies to target IncRNA
  3. Validate tools developed in WP2 to target telomeric RNA and alterative splicing
  4. Develop pipelines for splicing regulation together with Spoke7
  5. Collaborate with vertical Spokes

Methodology

SELEX, genome wide splicing profiles, epi-transcriptome analysis in collaboration with WP 6.1, cutting-edge positional sequencing, computational approaches in collaboration with Spoke7, mRNA and RNA cellular transfection, LC- MS MS, ASO chemical modification in collaboration with WP 6.2, transfer of know-how to vertical Spokes.

Task 6.3.1

Task 6.3.2

Task 6.3.3

Task 6.3.4

Task 6.3.1

Task Leader: Gabriella Viero
PI: Gabriella Viero, Stefania Bortoluzzi

PI: Stefania Bortoluzzi

T large granular lymphocyte leukemia (T-LGLL) is a lymphoproliferative disease whose pathogenesis is still not completely understood and for which a curative therapy is missing. The course of the disease is chronic with cytopenias, particularly neutropenia, being the clinical manifestations most impacting the patient quality of life and survival.Recent high-throughput...

PI: Gabriella Viero

RNA metabolism at large, and translation in particular, are increasingly recognized as defective hubs in untreatable conditions such as cancer and neurodegenerative diseases, from Alzheimer and Parkinson to Muscular Dystrophies. Ribosomes are the core of translation, which is the most energy consuming process in cells, with rRNA and tRNAs draining...

Task 6.3.2

Task Leader: Amelia Cimmino
PI: Amelia Cimmino, Pietro Laneve, Pierpaolo Ceci, Stefania Bortoluzzi

PI: Stefania Bortoluzzi

T large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disease whose pathogenesis is still not completely understood and lacking a curative therapy. We contributed to the definition of the genetic bases of T-LGLL and recently described the transcriptome aberrancies in this malignancy, collecting relevant preliminary data about the dysregulation...

PI: Pierpaolo Ceci

Objectives of the project -Long noncoding RNAs (lncRNAs) are expressed in a highly specific manner in cancer, where they function as oncogenes or oncosuppressors. This makes them powerful candidates as potential therapeutic targets. Human ferritin (HFt) is a multimeric protein-cage that self-assembles into a structure able to encapsulate drugs and...

PI: Pietro Laneve

My research group at IBPM has a track record in investigating the roles of RNA in neuronal biological models. Our specific focus lies in comprehending the biogenesis, regulation, and mechanisms of action of noncoding RNAs within various contexts, including neuronal cell fate determination, neuromuscular pathophysiology, and nervous system cancers. A...

PI: Amelia Cimmino

My team of researchers at IGB has an extensive record of exploring the functions of a particular class of non-coding RNA (ncRNA), referred to as transcribed ultraconserved RNA (T-UCRs), which was found computationally to have a “special property” identified as unique conservation across several genomes. The starting point is to...

Task 6.3.3

Task Leader & PI: Fabrizio D’Adda di Fagagna

 

PI: Fabrizio D’Adda di Fagagna

Telomere dysfunction (either following shortening or damage) and the ensuing DNA damage response (DDR) activation are associated with several pathologies and aging in several cells and organs, in various animals, including humans. What is its actual contribution to pathologies and to the aging process is presently unknown. This is in...

Task 6.3.4

Task Leader: Claudia Ghigna
PI: Claudia Ghigna, Giuseppe Biamonti, Alessandra Montecucco, Laura Poliseno, Claudia Coronnello

PI: Claudia Coronnello

Our group focuses on the development of bioinformatic tools useful to understand post-transcriptional regulatory mechanisms, like microRNA or long non-coding RNA activity. In this project, we will use the experimental results obtained with the ASO targeting AS to enrich a database useful to train machine learning based algorithms. Specifically, we...

PI: Laura Poliseno

Our group will conjugate the ASO with the “intelligent carrier” attenuated Listeria monocytogenes (Lmat). This strategy will allow us to couple strong on-target effects (Lmat-induced stimulation of host immune system against cancer cells plus ASO-induced reduction of tumor neo-vasculature) with minimal side effects, given that Lmat has selective tropism for...

PI: Alessandra Montecucco

My laboratory has been involved for a long time in the cell stress response, in particular in the cell response to DNA damage and metabolic stress. In the last ten years became evident that several pre-mRNA processing factors are regulated during the DNA damage response shifting the alternative splicing (AS)...

PI: Giuseppe Biamonti

My scientific activity focuses on the characterization of fundamental aspects of RNA processing. More recently my main interest was the analysis of alternative splicing (AS) deregulation in cancer progression. We showed that the level of splicing regulator SRSF1 controls the transition from epithelial to mesenchymal cell. Interestingly, the levels of...

PI: Claudia Ghigna

The overarching goal of Task 6.3.4 is the development of molecules and strategies to target alternative splicing events involved in heterogenous diseases, syndromes, and multi-systemic conditions currently lacking curative options. In light of the fact that a vigorous neo-vasculature development is characteristic of aggressive primary tumors and metastases and that...