ONDRI Scholars Promoting Novel Scientific Discoveries

The life of a researcher, whether a graduate student or working in a faculty position, can be a lonely one

The stereotype: pale, sleep-deprived, chained to a laptop in a basement, with limited human contact.

While the passion for the work and the possibility of novel scientific discoveries are strong motivators, the deeply specialized focus that is typical can contribute to research silos, limiting the potential for discovery.

ONDRI was built on a team science framework, with sharing and collaboration at its core. As data for ONDRI’s Foundational study was being collected, a team was pulled together to plan for data sets that would allow optimal collaboration with other research initiatives and for discoveries on a bigger scale. This team, pulled from various specialties, was called the “ONDRI Scholars”, and its focus has continued to develop over the years.

Doug Munoz, PhD, an ONDRI co-lead, helped develop the ONDRI Scholars framework and still leads it today. The structure allows researchers who would not typically be exposed to data from another specialty to not only freely access it, but also interact with specialists in that area. In-person Scholars meetings were set up to allow maximum personal interaction – formal & informal, professional & social – promoting the “magic” that comes when smart minds collide.

It was at such a meeting in 2018 that Allison Dilliott, a PhD candidate in Genetics, came to sit with Joel Ramirez, PhD, a (now senior) research associate working in Cognitive Neurology. Allison was analyzing genetic data using the ONDRI Seq panel. She had noticed that the rate of NOTCH3 gene variants in the ONDRI Parkinson’s cohort was higher than expected. Explaining these “weird patterns” she was seeing in the genetic data, Allison wondered if Joel was seeing similarly unexpected patterns in his brain imaging work.

NOTCH3 gene variants are typically associated with CADASIL, a small (blood) vessel disorder in the brain. Blood vessels disorders, which can have an impact on cognition, are not typically associated with Parkinson’s Disease patients. 

Back in his lab, Joel explored this issue and found similarly interesting patterns. Imaging data from the ONDRI Parkinson’s patients were shown to have:

• ‘white matter hyperintensities’; that is, localized changes in water content of ‘white matter’, which is found in small vessels, deep in the brain. This may indicate some type of injury to the brain, and
• even higher levels of ‘white matter hyperintensities’ for those individuals with the NOTCH3 variants

The presence of higher-than-expected white matter hyperintensities, and the additional connection with the NOTCH3 variants for these Parkinson’s Disease patients was an indication of something truly novel and exciting.

These observations led to many follow up conversations which eventually resulted in a paper recently published in the journal Movement Disorders.

“In genetics we don’t usually see deeply characterized data. I had a hunch I may be on to something but did not have the expertise to explore it as needed. This led me to Joel”, said Allison.

Had it not been for the Scholars framework at ONDRI, Joel and Allison would not have had the opportunity to have this conversation. What’s more, if it wasn’t for ONDRI’s standardized assessments, across five disease groups, there would likely be no imaging data on the patients described, as Parkinson’s patients do not typically get MRIs. Only the right combination of expertise in genetics, imaging and neurodegenerative diseases could have led to these observations. 

“Today, we are trying to make the ONDRI Scholars program more inclusive. If you are working in ONDRI in a research capacity and are interested in interacting and learning with a bunch of really smart people, having conversations that may be out of your comfort zone, you’re welcome to join our meetings”, said Munoz. “We really believe that magic happens when people come together from different disciplines, with an open mind and the same goals at a very high level, and ONDRI is the embodiment of that.”

To date ONDRI has trained over 200 Highly Qualified Personnel in multiple labs and over a dozen institutions across Ontario.