Periodic Reporting for period 1 - RBP-ReguNet (Deconstructing and Rewiring RNA-RBP regulatory networks)
Berichtszeitraum: 2023-03-01 bis 2025-02-28
RNA-binding proteins (RBPs) regulate RNA processes, including transcription, splicing, translation, and decay, and disruptions in these networks are linked to various diseases. Recent studies have expanded the RBP repertoire, uncovering unconventional RBPs like metabolic enzymes with RNA-binding roles. RBP-ReguNet aims to explore these findings for druggable targets in diseases like cancer and neurological disorders, providing advanced training for European researchers to develop RBP-based therapies.
Key objectives:
1. Identify RBPs in demyelinating diseases and liver pathologies.
2. Identify key RBPs impacting biological processes in pathological models.
3. Characterize novel RBP molecular functions.
4. Identify small molecule inhibitors for RBPs.
5. Provide high-level training for researchers.
Key objectives:
1. Identify RBPs in demyelinating diseases and liver pathologies.
2. Identify key RBPs impacting biological processes in pathological models.
3. Characterize novel RBP molecular functions.
4. Identify small molecule inhibitors for RBPs.
5. Provide high-level training for researchers.
This project investigates RNA-binding proteins (RBPs) and their roles in diseases like cancer, neurodegeneration, and metabolic disorders, paving the way for new treatments.
Key discoveries include the identification of QKI and CELF2 as crucial for myelination, offering insights into Charcot-Marie-Tooth disease. CIRBP was found to regulate liver fibrosis progression, shedding light on its inflammatory role. In cancer research, better understanding of the MAPK pathway, implicated in 30-50% of cancers, may help develop targeted therapies. RBM10’s role in pancreatic cancer proliferation was also identified, suggesting potential intervention strategies.
Advancements in T-cell function mapping under stress and normal conditions were made using cutting-edge multiplexing technology, improving sensitivity and efficiency. A reconstituted cell-free translation system (ReCet) was developed, enabling efficient protein synthesis outside living cells for synthetic biology, drug discovery, and biotechnology.
In melanoma, CRISPR/Cas9 screening revealed RBPs regulating CD155 immune checkpoint expression. Initial tests of small-molecule inhibitors provided new immune-targeting insights. Small-molecule inhibitors for HuR and YTHDF2 were identified, offering new therapeutic possibilities, alongside PROTAC technology for targeted protein degradation.
Research on RNA-mediated metabolic enzyme regulation is ongoing, with potential breakthroughs in riboregulation. A long-term goal is to determine the structure of human ENO1 with an RNA inhibitor, offering novel insights into metabolic control.
These discoveries and innovations have significant implications for advancing diagnostics and treatments across multiple diseases.
The project also explores the role of the autophagy adaptor p62/SQSTM1 in viral infections, particularly SARS-CoV-2. Using engineered Huh-7 liver cancer cells expressing the ACE2 receptor, researchers examined the impact of p62 knockout on viral gene expression. The study extended to other RNA viruses, including Zika, Coxsackievirus, human coronavirus OC43, and Sindbis virus, to assess p62’s broader relevance in viral pathogenesis.
Key discoveries include the identification of QKI and CELF2 as crucial for myelination, offering insights into Charcot-Marie-Tooth disease. CIRBP was found to regulate liver fibrosis progression, shedding light on its inflammatory role. In cancer research, better understanding of the MAPK pathway, implicated in 30-50% of cancers, may help develop targeted therapies. RBM10’s role in pancreatic cancer proliferation was also identified, suggesting potential intervention strategies.
Advancements in T-cell function mapping under stress and normal conditions were made using cutting-edge multiplexing technology, improving sensitivity and efficiency. A reconstituted cell-free translation system (ReCet) was developed, enabling efficient protein synthesis outside living cells for synthetic biology, drug discovery, and biotechnology.
In melanoma, CRISPR/Cas9 screening revealed RBPs regulating CD155 immune checkpoint expression. Initial tests of small-molecule inhibitors provided new immune-targeting insights. Small-molecule inhibitors for HuR and YTHDF2 were identified, offering new therapeutic possibilities, alongside PROTAC technology for targeted protein degradation.
Research on RNA-mediated metabolic enzyme regulation is ongoing, with potential breakthroughs in riboregulation. A long-term goal is to determine the structure of human ENO1 with an RNA inhibitor, offering novel insights into metabolic control.
These discoveries and innovations have significant implications for advancing diagnostics and treatments across multiple diseases.
The project also explores the role of the autophagy adaptor p62/SQSTM1 in viral infections, particularly SARS-CoV-2. Using engineered Huh-7 liver cancer cells expressing the ACE2 receptor, researchers examined the impact of p62 knockout on viral gene expression. The study extended to other RNA viruses, including Zika, Coxsackievirus, human coronavirus OC43, and Sindbis virus, to assess p62’s broader relevance in viral pathogenesis.
This project investigates RNA-binding proteins (RBPs) and their roles in diseases like cancer, neurodegeneration, and metabolic disorders, paving the way for new treatments.
Key discoveries include the identification of QKI and CELF2 as crucial for myelination, offering insights into Charcot-Marie-Tooth disease. CIRBP was found to regulate liver fibrosis progression, shedding light on its inflammatory role. In cancer research, better understanding of the MAPK pathway, implicated in 30-50% of cancers, may help develop targeted therapies. RBM10’s role in pancreatic cancer proliferation was also identified, suggesting potential intervention strategies.
Advancements in T-cell function mapping under stress and normal conditions were made using cutting-edge multiplexing technology, improving sensitivity and efficiency. A reconstituted cell-free translation system (ReCet) was developed, enabling efficient protein synthesis outside living cells for synthetic biology, drug discovery, and biotechnology.
In melanoma, CRISPR/Cas9 screening revealed RBPs regulating CD155 immune checkpoint expression. Initial tests of small-molecule inhibitors provided new immune-targeting insights. Small-molecule inhibitors for HuR and YTHDF2 were identified, offering new therapeutic possibilities, alongside PROTAC technology for targeted protein degradation.
Research on RNA-mediated metabolic enzyme regulation is ongoing, with potential breakthroughs in riboregulation. A long-term goal is to determine the structure of human ENO1 with an RNA inhibitor, offering novel insights into metabolic control.
These discoveries and innovations have significant implications for advancing diagnostics and treatments across multiple diseases.
Key discoveries include the identification of QKI and CELF2 as crucial for myelination, offering insights into Charcot-Marie-Tooth disease. CIRBP was found to regulate liver fibrosis progression, shedding light on its inflammatory role. In cancer research, better understanding of the MAPK pathway, implicated in 30-50% of cancers, may help develop targeted therapies. RBM10’s role in pancreatic cancer proliferation was also identified, suggesting potential intervention strategies.
Advancements in T-cell function mapping under stress and normal conditions were made using cutting-edge multiplexing technology, improving sensitivity and efficiency. A reconstituted cell-free translation system (ReCet) was developed, enabling efficient protein synthesis outside living cells for synthetic biology, drug discovery, and biotechnology.
In melanoma, CRISPR/Cas9 screening revealed RBPs regulating CD155 immune checkpoint expression. Initial tests of small-molecule inhibitors provided new immune-targeting insights. Small-molecule inhibitors for HuR and YTHDF2 were identified, offering new therapeutic possibilities, alongside PROTAC technology for targeted protein degradation.
Research on RNA-mediated metabolic enzyme regulation is ongoing, with potential breakthroughs in riboregulation. A long-term goal is to determine the structure of human ENO1 with an RNA inhibitor, offering novel insights into metabolic control.
These discoveries and innovations have significant implications for advancing diagnostics and treatments across multiple diseases.