Exploring Splicing Alterations in Neurological Disorders to Develop Targeted Therapeutics
- High-Throughput Screening Platform for Non-Coding Variants in Neurodevelopmental Disorders (NDDs):
Non-coding variants, which make up 70% of disease-causing mutations, remain poorly understood in their contribution to NDDs. To address this gap, we are developing Prime Editing Single-Cell Splice Sequencing (PE-scSpliceSeq), a platform that integrates prime editing and single-cell RNA sequencing. This platform enables precise functional characterization of non-coding variants by introducing them into iPSC-derived neurons, offering insights into their impact on mRNA splicing and downstream molecular pathways.
Impact: PE-scSpliceSeq has the potential to revolutionize our understanding of non-coding variants and provide transformative insights into NDDs. - The Role of Poison Exons in Neurological Diseases:Poison exons regulate protein expression through mechanisms like nonsense-mediated decay. We have identified 217 pathogenic variants in poison exons linked to disorders like Alzheimer’s, epilepsy, and lysosomal storage diseases. Ongoing validation uses genome editing and minigene assays. This work, supported by an NIH R01 grant, sheds light on critical neuronal processes and offers opportunities for innovative splicing-based therapies.
- Gene Editing for Familial Dysautonomia (FD):We are developing base editing therapies to correct the ELP1 splicing mutation causing FD. Initial efforts focus on preventing retinal degeneration, with a long-term goal of systemic correction. Our combinatorial strategy integrates splicing modulators with gene editing for a comprehensive treatment, aiming to alleviate the broader neurological symptoms of FD.
- Splicing Modulators for Frontotemporal Dementia (FTD): We are optimizing splicing modulators to target MAPT exon 10, mitigating toxic tau accumulation in FTD. Our compounds have shown efficacy in FTD-derived neuronal and mouse models. Future work aims to advance these modulators to clinical applications.
The revitalized art gallery is set to redefine cultural landscape.
With meticulous attention to detail and a commitment to excellence, we create spaces that inspire, elevate, and enrich the lives of those who inhabit them.
The revitalized Art Gallery is set to redefine the cultural landscape of Toronto, serving as a nexus of artistic expression, community engagement, and architectural marvel. The expansion and renovation project pay homage to the Art Gallery’s rich history while embracing the future, ensuring that the gallery remains a beacon of inspiration.
The revitalized Art Gallery is set to redefine the cultural landscape of Toronto, serving as a nexus of artistic expression, community engagement, and architectural marvel. The expansion and renovation project pay homage to the Art Gallery’s rich history while embracing the future, ensuring that the gallery remains a beacon of inspiration.
Guiding your business through the project
Experience the fusion of imagination and expertise with Études—the catalyst for architectural transformations that enrich the world around us.
Meet our team
Elisabetta Morini, Ph.D.
Principal Investigator
Assistant Professor of Neurology, Massachusetts General Hospital and Harvard Medical School
Associate Member, Broad Institute of MIT and Harvard
Research Focus: Splicing regulation in neurological disorders and therapeutic development.
Paolo Pigini, Ph.D.
Postdoctoral Fellow.
Focus: RNA-based therapies for neurodegenerative diseases.
Hannah Lindmeier, B.S.
Research Technician.
Focus: FTD iPSC-derived neurons, tau expression analysis, viability assays, and neuronal marker evaluation.
Yan Ju, B.S.
Research Technologist.
Focus: RNA metabolism in juvenile ALS and FTD.
We’ve worked with some of the best companies.
FAQs
What is your process working in smaller projects?
Études offers comprehensive consulting, management, design, and research solutions. Our vision is to be at the forefront of architectural innovation, fostering a global community of architects and enthusiasts united by a passion for creating spaces. Every architectural endeavor is an opportunity to shape the future.
Who is behind Études?
Études offers comprehensive consulting, management, design, and research solutions. Our vision is to be at the forefront of architectural innovation, fostering a global community of architects and enthusiasts united by a passion for creating spaces. Every architectural endeavor is an opportunity to shape the future.
I’d like to get to meet fellow architects, how can I do that?
Études offers comprehensive consulting, management, design, and research solutions. Our vision is to be at the forefront of architectural innovation, fostering a global community of architects and enthusiasts united by a passion for creating spaces. Every architectural endeavor is an opportunity to shape the future.
Can I apply to be a part of the team or work as a contractor?
Études offers comprehensive consulting, management, design, and research solutions. Our vision is to be at the forefront of architectural innovation, fostering a global community of architects and enthusiasts united by a passion for creating spaces. Every architectural endeavor is an opportunity to shape the future.
Enhance your architectural journey with the Études Architect app.
- Collaborate with fellow architects.
- Showcase your projects.
- Experience the world of architecture.