Cure SMA has awarded a $30,000 research grant to Jocelyn Cote, PhD, at the University of Ottawa for his project, “The role of SMN as a translational regulator.”

Because of a genetic mutation in the SMN1 gene, individuals with SMA don’t produce survival motor neuron protein (SMN protein) at high enough levels. We know this causes motor neurons to stop working correctly and eventually die, but researchers are also looking at the other effects the loss of SMN protein has on the body.

Dr. Cote and his team have discovered that SMN plays a critical role in the regulation of protein production, called “translation.” This grant will allow them to further investigate the impact this has on the body. Understanding how the loss of SMN protein affects translation, along with other important processes, could reveal more about where and when the protein is needed in order to effectively treat SMA.

The grant to Dr. Cote is funded by Families of SMA Canada.

Meet Dr. Cote

Who are you?

I obtained my PhD from the University of Sherbrooke in the province of Quebec, Canada. I then pursued my training as a Postdoctoral Fellow at Washington University in St.-Louis in the US and at McGill University in Montreal, Qc, Canada. I started my independent research group at the University of Ottawa in 2004 and I am now a Professor in the Department of Cellular and Molecular Medicine.

I am a biochemist and molecular biologist by training with specific expertise in the field gene expression regulation, including a process called transcription that turn genes on and process called translational that produces protein. Transcription involves the synthesis of so-called messenger RNA from a DNA template resulting in the transfer of genetic information from the DNA molecule to the messenger RNA. The messenger RNA is then used to produce protein.

How did you first become involved with SMA research?

Coming from a biochemical background, I initially started working on SMA because I identified a part of the SMN protein called the Tudor domain, which can interact with other proteins tagged with a modification termed ‘arginine methylation’. Following this discovery, we reasoned that some of the methylated proteins might not function normally in the absence of SMN in SMA patients, and that studying these proteins might help us gain a better understanding of what SMN does in spinal cord motor neurons and how loss of its activity leads to SMA. Although it started primarily as a scientific question, after I first attended the Annual Cure SMA Research Conference back in 2002 and met with SMA kids and their families, it became clear to me that I was going to do my best to contribute my expertise towards increasing our fundamental understanding of this disease in the hope that it would help one day in the elaboration of novel therapeutic strategies.

What is your current role in SMA research?

My lab uses biochemical and cellular biology approaches, working with various animal and cellular models of SMA, in order to gain a better understanding of the precise function that SMN plays in spinal cord motor neuron, and how loss of that function leads to the disease. For example, we are trying to identify what are the other proteins and RNA molecules that SMN interacts with and controls in motor neurons, with the logic that this should give us some insights into what SMN is actually doing in this cell type in particular. Then, we assess if these SMN interacting partners could represent valid targets for SMA drug development.

What do you hope to learn from this research project?

We have been the first to describe a new function for SMN in the regulation of protein production (called translation) and will perform further experiments to gain a better understanding of how SMN goes about doing this new function. We will also determine the consequences of losing this function in cells from SMA patients.

How will this project work?

We propose to use a series of biochemical, molecular and cellular approaches that will allow us to (i) determine the composition of the complexes in which SMN functions to control translation or protein production in motor neurons; (ii) identify the subset of mRNAs that are regulated by SMN and determine whether these are misregulated in SMA; and (iii) explore the therapeutic potential of increasing the levels and/or activity of regulators of SMN function in SMA cells in order to compensate for loss of SMN.

What is the significance of your study?

The current proposal will provide crucial insights into a novel function for SMN in spinal cord motor neurons. The identification of the molecular targets that are misregulated due to loss of this novel SMN function in SMA should lead to a more complete understanding of disease mechanism (including tissue specificity) and has the potential to identify novel therapeutic targets.

Basic Research Funding

This grant to Dr. Cote 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.

Past Announcements

$140,000 to Megerditch Kiledjian, PhD

$140,000 to Rashmi Kothary, PhD

$140,000 to Christine Beattie, PhD

$90,000 to Antoine Cléry, PhD

$140,000 to Arthur Burghes, PhD