This article is part of a series of Cure SMA grant announcements that will be shared throughout the next couple of months.

Cure SMA has awarded a $150,000 grant to Dmytro Morderer, Ph.D., of the Mayo Clinic in Jacksonville, Fla., for his project titled, “Effect of SMN deficiency on ribonucleoprotein assembly.” Dr. Morderer is a post-doctoral researcher working in the laboratory of Dr. Wilfried Rossoll.

Dr. Morderer is one of three 2020 recipients of the Audrey Lewis Young Investigator Award, periodically given to younger researchers working in the SMA field. Audrey Lewis founded Families of SMA, now Cure SMA, and the goal of this legacy award is to make a positive impact on the early phase of a talented researcher’s career, enabling them to focus on the SMA field and efforts to develop a treatment and cure for SMA.

Dr. Morderer will study the role of SMN in the assembly of ribosomes—large complexes of RNA and protein that act as cellular factories for making proteins—and why they are impaired in SMA due to low levels of SMN protein. Understanding how low levels of SMN impact this important cellular function may uncover novel therapeutic targets.

Meet Dr. Morderer

Tell us about your work?

I have been trained as a molecular biologist at the Taras Shevchenko National University of Kyiv and earned my Ph.D. at the Institute of Molecular Biology and Genetics in Kyiv, Ukraine. During my Ph.D., I studied interactions between different proteins in cells by using common biochemical techniques. I also developed a strong interest in studying neurodegenerative diseases. In 2017, I began working in the Department of Neuroscience at the Mayo Clinic in Jacksonville, Fla. In my current research, I combine classical methods of molecular and cellular biology with novel proteomics approaches that allow us to monitor changes of thousands of proteins in one experiment.

How did you first become involved with SMA research?

I was first introduced to ongoing SMA research by Dr. David Pastre from the University of Evry, France, who was a collaborator with my lab when I was a Ph.D. student. I found it fascinating how low levels of SMN protein, which is present in all the cells in our bodies, can cause such specific damage to motor neurons. I thought it would be interesting to work on this fascinating scientific challenge after getting my Ph.D. During a training course in Analysis and Integration of Transcriptome and Proteome Data at the European Molecular Biology Laboratory in Heidelberg, Germany, I met Dr. Wilfried Rossoll, who offered me a postdoctoral position in his newly established lab at the Mayo Clinic. Since then, I have been working on a project to study the role of SMN in the assembly of protein and RNA molecules. I was fortunate to attend the Cure SMA Annual SMA Conference in 2018, where I had a chance to meet both SMA scientific and patient communities.

What is your current role in SMA research?

In our SMA research, we use cellular and animal models of SMA to find out how low levels of SMN affect molecular processes that occur in cells. We are mostly focused on studying the assembly of complexes that include both RNA and protein molecules, also called ribonucleoproteins. These complexes play a pivotal role in ensuring proper execution of the genetic programs encoded by our genes. The SMN protein is an important regulator of ribonucleoprotein formation, and when this protein is missing or mutated, the molecular assembly and functions of ribonucleoproteins are impaired. We aim to determine the extent and the exact nature of these impairments, how they may contribute to motor neuron degeneration, and how we may be able to rescue these defects.

What do you hope to learn from this research project?

The objective of this proposal is to find out what proteins bind RNA differently and how the assembly of ribosomes—large complexes of RNA and protein that act as cellular factories for protein synthesis—are impaired in SMA.

How will this project work?

We will fix all RNA-binding proteins to their RNAS in both normal cells and cells with low levels of SMN protein (SMA cells). This will allow us to identify and quantify all these proteins that were bound by RNA and compare their abundance in normal and SMA cells. We will also take healthy mice and SMA mice, isolate the ribosomes in their motor neurons, and determine differences in protein and RNA content between ribosomes from unaffected and SMA model mice.

What is the significance of your study?

Despite the great progress in SMA therapy and years of extensive research, we still don’t know why motor neurons die when they have low levels of SMN protein. Our project is aimed to find out what cellular processes are impaired by low levels of SMN, so that we can identify specific therapeutic targets for novel treatments that can be combined with existing SMN-enhancing therapeutics.

About Cure SMA’s Basic Research Funding

This grant to Dr. Morderer is part of $1,100,000 in new basic research funding that we are currently announcing. 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.