Cure SMA has awarded a $90,000 research grant to Antoine Cléry, PhD, at ETH Zurich for his project, “Novel approaches against spinal muscular atrophy by targeting splicing regulators.”
SMA is caused by a mutation in the SMN1 gene, which regulates the production of survival motor neuron (SMN) protein. Individuals with SMA also have one or more copies of SMN2, the SMA “backup gene.” SMN2 also produces SMN protein, but most of the protein produced by SMN2 is lacking a key piece, called exon 7.
Dr. Clery’s project will investigate different molecules that might affect the splicing of SMN2. If the splicing of SMN2 is corrected, then it would be able produce higher amounts of complete SMN protein.
Meet. Dr. Clery
Who are you?
I am a senior researcher working in Frédéric Allain’s lab at ETH Zürich, which is specialized in the structure determination of protein-RNA complexes using NMR. I performed my PhD in molecular biology and a post-doc in structural biology (NMR). I am studying protein-RNA interactions involved in the splicing regulation of SMN2 mRNA.
How did you first become involved with SMA research?
I was working on the structure determination of the splicing regulator Tra2-β1 when I started to study the mode of regulation of this protein on SMN2 mRNA splicing.
What is your current role in SMA research?
I aim at finding new therapeutic strategies to cure SMA. We are trying to engineer the splicing regulator SRSF1 to force it to promote SMN2 exon7 inclusion. In parallel, we would like to identify small molecules that reinforce the activity of splicing factors that activate SMN2 exon7 inclusion.
What do you hope to learn from this research project?
We aim to identify a new generation of molecules that control the protein splicing regulators of the SMN2 pre-mRNA. Understanding this could lead to promising drugs against SMA and other splicing-related diseases.
How will this project work?
We will screen chemical compound libraries against protein splicing regulators bound to their SMN2 RNA. In addition, we will use our protein structural data to specifically assess the role of a protein-splicing regulator called SRSF1 protein that binds SMN2 exon7 and promotes exon7 inclusion in mature SMN2 mRNAs.
What is the significance of your study?
There is still no treatment for SMA and other splicing-related diseases. Finding new therapeutic strategies to approach these disease that act specifically on splicing regulators is a very promising method to correct splicing defects.
Basic Research Funding
This grant to Dr. Clery is part of $890,000 in new basic research funding that we’re currently announcing. Please see below for links to other recent announcements.
Basic research is the first step in our comprehensive research model. We fund basic research to investigate the biology and cause of SMA, in order to identify the most effective strategies for drug discovery. We also use this funding to develop tools that facilitate SMA research.
$140,000 to Megerditch Kiledjian, PhD
$140,000 to Rashmi Kothary, PhD