NeuroRBP · Studying RNA-binding proteins involved in neural differentiation and degeneration
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-06-01 → 2021-05-31
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Studying RNA-binding proteins involved in neural differentiation and degeneration
RNA-binding proteins (RBPs) regulate multiple levels of gene expression. Furthermore, RBPs support biomolecular condensate development, and contribute to the functionality of enhancers, transcription factors and RNA Pol II. Mutations and dysregulated expression of RBPs may lead to neurodegeneration. The main question of this project is why are neurons very sensitive to the malfunction of RBPs? And how does this malfunction end up to neurodegenerative disorders? At the moment, there is no successful therapy to treat devastating symptoms of neurodegenerative disorders. Considering the sever demand, there are extensive efforts to develop novel therapeutic approaches. For Europe, as a research-based society and economy, these studies are crucial to achieve a leading global position in the field of molecular biology. This project helps to understand the pathways involved in neurodegenerative diseases from chromatin and RBP perspectives, and to develop more effective treatments. In this study we aimed to develop a highly sensitive method to study dynamics of chromatin-binding in RBPs. We used the method to compare motor neurons obtained from patient-derived iPS cells with control cells. As a result, we shed light on the mechanism that makes the motor neurons vulnerable to DNA damage.
Data: CORDIS, © European Union
Project objective
RNA-binding proteins (RBPs) coordinate post-transcriptional regulation immediately after transcription by RNA-processing, nuclear export, localization, stability and translation rate of RNAs. The importance of these RBPs in neural development have been underscored by detecting their mutations in severe neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), ataxia or tremor. In this project, using the assays that I developed specifically for the identification of RBPs I want to track down novel RBPs involved in neural differentiation. I will use patient-derived induced pluripotent stem cells (iPSC), as model system to discover RBPs that their malfunction may lead to neurodegeneration. Furthermore, I will identify the binding targets of the RBPs to determine the pathways that are affected. Finally, using machine-learning methods I will integrate these data to shed new light on the mechanism of neural differentiation and degeneration. The output of this project in long term will help to identify individuals at risk, and to develop better therapeutic approaches to treat neurodegenerative diseases.
Original text from CORDIS.
Participants
- THE FRANCIS CRICK INSTITUTE LIMITED · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union