How genetics shape neurodevelopmental disorders

U of M professor explores the genetic roots of brain disorders

Robert Beattie is an assistant professor of biochemistry and medical genetics in the U of M’s Rady faculty of health science.

Beattie began his undergraduate studies in microbiology at U of M and later joined the science co-op program. One of his first experiences was at the national microbiology laboratory, where he worked on Ebola vaccine development, enhancing his understanding of molecular biology and the significance of virus research.

Beattie studied developmental neurobiology during a co-op term at the Max Planck Institute in Germany.

“It [was] fundamental research and [the] initial experience that set me on this journey to where I am today,” he said.

When Beattie returned to Manitoba, he completed an honours project with Steve Wired, who remains an inspiration and a mentor. Wired taught him key molecular biology skills and the use of advanced technologies in developmental biology.

Beattie then pursued graduate studies in Europe, returning to the lab where he once completed his co-op program.

“This was split between both the University of Sheffield and the University of Basel in Switzerland. There, I studied neurodevelopment neuro stem cells, and I got to understand why this was a field I wanted to continue with,” he said.

Beattie was drawn to the research due to its potential to benefit many individuals. Defects in neural stem cells can result in conditions such as microcephaly, macrocephaly, autism and psychiatric disorders like schizophrenia.

A solid understanding of molecular biology is essential for studying these disorders, he explained. After completing his PhD, he continued his academic journey by pursuing a postdoctoral position in Vienna, Austria, which is a common path in the field of biomedical sciences.

Beattie credited Simon Hippenmeyer, a professor in the field, for inspiring and mentoring him in the development of advanced technologies used in his lab. Their collaboration resulted in groundbreaking research that brought Beattie back to the U of M, where he established his own lab in the department of biochemistry and medical genetics.

His current research focuses on how large copy number variants contribute to disorders such as microcephaly, autism spectrum disorder and schizophrenia. Additionally, his team investigates neurodevelopmental processes, including the role of the DNA repair enzyme FAN1 in conditions like Rett syndrome and Huntington’s disease.

“My past research has been studying neural stem cells and their lineage in the brain,” he said.

“During my postdoc, we identified some of these regulators that regulate the switch from neurogenic to gliogenic, meaning the production of neurons to the production of glial. This switch is critical [for] producing the right number of neurons and glial in the brain.”

Beattie continues this research in his current lab, focusing on the genetic factors that contribute to various neurodevelopmental disorders.

His team uses an advanced technique called Mosaic Analysis with Double Markers (MADM) to generate genetic mosaics in mice. This approach traces the lineage of stem and progenitor cells in the brain.

“We can create a mouse [with] a mutant cell for any gene we’re interested in studying, and a wild-type cell for the same gene, and track those cells over time,” he said. “The mutant cells could be labelled green, the wild-type cells could be labelled red, and then we can watch and see how those cells develop over time in different environments.

“This approach is unique to my lab in Canada.”

Beattie explained that his research also examines what occurs inside a cell when a gene is disrupted. MADM is one of the few technologies that enable the study of health and disease at the single-cell level, making it a powerful tool for research.

In his lab, researchers use this approach to investigate various diseases such as autism, Rett syndrome and schizophrenia, to understand changes occurring at the cellular level.

“As we learn more about different diseases or disorders, we begin to realize that there is a lot of cellular heterogeneity,” he explained.

“When a tissue is affected by a certain disease, not all cells will respond the same. Some cells might not function correctly while other cells continue to function as normal,” he said. “Using these single-cell technologies, we can now study disease at single-cell resolution, and that’s the future of identifying the cause of cellular heterogeneity in disease. But also if we wish to develop future patient-specific therapeutics.”

Beattie encouraged students to explore research opportunities, as they offer valuable experience and guidance.

“As an undergrad student, you have so many opportunities and directions that you can go in, and it’s really important to take full advantage of those opportunities at that stage,” he said.