Drs. Maria Stepanova and Holger Wille: Two researchers bring together diverse expertise, from physics to structural biology, to find new insights

Can computational methods aid in the design of key antibodies for the diagnosis and treatment of ALS?

Award: $125,000

Dr. Maria Stepanova, a physicist at the University of Alberta, is one of nine 2022 ALS Canada-Brain Canada Discovery Grant recipients. She works closely with Dr. Holger Wille, a structural biologist also at U of A. Though both have decades of experience researching other neurodegenerative diseases, the grant represents their first time being funded for ALS research.  

“We are new to the ALS field, so it’s nice to get funded for some of our ideas and see what we can contribute,” says Dr. Wille.  

As early as junior high, Dr. Stepanova had a passion for scientific inquiry, hoping to become either a physicist or a biologist. She began her career as the former, studying how complex structures, such as crystals, could arise from seemingly simple interactions between atoms.  

“I chose physics at the beginning because it allowed me to start with the very basics,” she says.  

Her relentless scientific curiosity has, in time, led her back to biology, where she takes a theoretical approach to understand how complex biological structures arise. 

This experience underpins her 2022 Discovery Grant project.  

A common hallmark of ALS is the presence of proteins, such as FUS or TDP-43, that have left their proper home in a cell, become misshapen and possibly no longer function properly. Drs. Stepanova and Wille’s project is based on what’s called the Prion Hypothesis, the idea that these misfolded proteins can transmit their abnormal structure to normal versions of the same protein, creating clumps or aggregates that spread throughout the nervous system. 

Dr. Stepanova’s lab will use computational methods to analyze these aggregates in ALS-specific proteins. In doing so, she hopes to find areas of the complex shapes for which an antibody could be made.  

Dr. Wille’s team will then take her data to attempt to create antibodies that could bind to and, theoretically, stop the misshapen proteins from spreading their abnormal shape. 

This process – analyzing misfolded proteins and creating disease-specific antibodies – is one the collaborators have used before in work on other neurodegenerative diseases, such as Alzheimer’s or Parkinson’s. It’s the first time they will take this approach to ALS.  

If successful, the project could be the first step in validating new ALS treatment sites or new biomarkers.  

Working with Dr. Wille has allowed Dr. Stepanova to bring her theoretical expertise to experiments with possible clinical impact.  

“Dr. Stepanova and I have collaborated for a long time on the theoretical side,” Dr. Wille says. “My team and I are the ones who try to translate things into practical experiments.” 

By bringing together their complementary skills, the pair look forward to contributing new knowledge to the field of ALS research.  

“This is truly what’s important to us,” says Dr. Viviane Poupon, President and CEO of Brain Canada. “Collaboration and knowledge sharing to advance brain research and magnify the potential for impact.”

Our goal is to find insights that would be interesting, enriching, and useful for the community on the way toward the development of new treatments of ALS. And we will do our best to achieve whatever we can in two years.”

Dr. Maria Stepanova, 2022 Discovery Grant Recipient

The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.  

To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.