Overview

In this call for applications, we seek to support research projects that deepen our understanding of the molecular events “downstream of RNA transcription” that diversify gene expression and function in embryonic and early postnatal development of the nervous system. The emphasis is on how these mechanisms contribute to normal nervous system development, physiological homeostasis and/or neural cell function, and how their dysfunction may contribute to neurodevelopmental disorders. Discoveries made possible by this RFA could lead to the development of mechanism-based interventions that address the fundamental molecular features that underlie neurodevelopmental conditions.   

 

Funding 

Individual or team projects will be funded to a maximum of $150,000 CAD per year for a maximum of three years. We expect to fund the top six applications, as determined by an external peer-review process.   

 

Topic Eligibility 

  • Post-transcriptional regulation of gene expression, including, for example, (but not limited to): RNA splicing, stability and localization; circular RNA biogenesis and function; regulation of RNAs by miRNA and RNA binding proteins (RBP); composition and role of RNA-associated granules and bodies 
  • Regulation of protein translation, including (but not limited to): Ribosome elongation, termination and quality control; localization of protein translation; regulation of protein degradation; Phase separation of protein complexes 
  • Spatial and temporal regulation of the above post-transcriptional/post-translational mechanisms in neuronal development and/or associated neurodevelopmental conditions 

We will accept applications using any relevant model/experimental system, provided the focus is relevant to the nervous system. 

RNA and the Brain Awardees

Sarah Hughes

University of Alberta

Grant title: Investigating how SMARCB1 post-transcriptional regulation regulates normal brain development is linked to development of autism

Description: This study uses fruit flies to determine the function of a molecule called SMARCB1 in normal brain development. SMARCB1 controls whether genes are on or off and was found to be different in individuals with autism spectrum disorder. Understanding what it does in the nervous system of a simple animal will inform how it causes autism.

Loydie Jerome-Majewska

Research Institute of McGill University Health Centre

Grant title: Impact of Spliceosomal Defects on Early Brain Development

Description: The human genome contains the code necessary to produce all the proteins that make up the living organism. But first, the genomic DNA must be converted into an intermediary RNA molecule, which in turn needs to undergo extensive modifications before it can be translated into a protein. One of the most important aspects of RNA processing is called splicing, where long segments of RNA are removed and a much more compact version – the messenger (m)RNA – is produced. Alternative splicing of these regions allows for a large number of diverse mRNAs and proteins to be created. This process is thought to be particularly important in the normal developing brain. This research will explore how splicing differences in genes related to neurodevelopmental disorders affects brain development.

David Kaplan and Freda Miller

Hospital for Sick Children

Grant title: Translating neural precursor cells to neurons and glia during normal and abnormal murine brain development

Description: The Kaplan-Miller research team will investigate how regulation of protein translation (the process of creating proteins from mRNA) in neural stem cells determines how many and what type of cells are formed in the brain during development, and how this process is disrupted in neurodevelopmental disorders.

Nahum Sonenberg

McGill University

Grant title: Single-cell mRNA translational control mechanisms in diverse forms of synaptic plasticity in an intact circuit of the developing primary visual cortex and in autism spectrum disorder

Description: Dr. Sonenberg’s team will investigate the molecular changes, mediated by the cell protein synthesis machinery, that modulate the strength of the synapses (i.e., the communication junctions between neurons), in health and neurodevelopmental disorders. Mechanisms that control protein synthesis are dysregulated in the brain of mouse models of neurodevelopmental disorders and can be targeted to rescue the deficits. This research should advance the understanding of the mechanisms by which neurons transmit signals in health and disease.

Wayne Sossin

McGill University/The Montreal Neurological Institute

Grant title: Determining how stalled polysomes are generated for transport in RNA granules and regulated local translation

Description: This project will find out exactly how the process of protein translation (the process of creating proteins from mRNA) in the nervous system is different in neurodevelopmental disorders.

Guang Yang

University of Calgary

Grant title: Dissecting and Targeting mRNA Regulation in Brain Development

Description: Dr. Yang previously identified a gene called CELF2, that is affected in patients with a rare neurodevelopmental condition. This project will study how CELF2 regulates neural precursor cells’ decisions on when to divide and become the right cell type, at the right time during development, using mice and human cells as model systems.

Ryan Yuen

Hospital for Sick Children

Grant title: Investigating repeat-mediated RNA dysregulation in autism spectrum disorder

Description: This study will address how short sequences that are repeated in the human genome contribute to neurodevelopmental disorders by changing the way that the genome’s code is read in the cells. This research will provide a new perspective on genetic inheritance of neurodevelopmental disorders.

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