Ryan Hallam (BSc ’18) had a lot in common with his current PhD supervisor, Aleksandar Necakov, during his days as an undergraduate Neuroscience student.

Hallam and the Associate Professor of Biological Sciences were relatively new to Brock. And both had been deeply impacted by a loved one living with Alzheimer’s disease.

“I got really interested in the work Dr. Necakov was doing in his molecular biology research program, which I learned about when he guest lectured for one of my second-year classes,” says Hallam.

He began working in Necakov’s lab with the support of a Brock Match of Minds student research grant. That experience, and the support of Necakov as a mentor, had a significant impact on Hallam.

“After being exposed to cutting-edge research, my grades went up dramatically the following year, because all the basics being learned in class became much easier to understand,” he says.

Fast forward several years and Hallam returned to Brock to pursue his PhD in the Necakov lab, where he has made advancements in Alzheimer’s research and received the prestigious Alzheimer Society Research Program’s Postdoctoral Award.

Hallam studies interactions among various proteins and enzymes in the brain associated with Alzheimer’s.

The brain contains a large protein called amyloid precursor protein (APP). Two enzymes — gamma secretase and beta secretase — cut APP into smaller fragments called amyloid beta  which then form amyloid plaques.

People living with Alzheimer’s have an excess number of amyloid plaques in their brains, along with build-ups of a protein called tau.

Hallam’s research focused on understanding more about how gamma secretase and beta secretase work, but he faced a big challenge.

“Studying what happens in patients’ brains at the molecular level is extremely difficult,” he says.

To get around that obstacle, he examined brain cells generated from stem cells but encountered a second major problem.

“The proteins and enzymes in these brain cells are extremely small,” he says. “If you’re looking at a whole cell, there’s tens of millions of proteins, there’s DNA, there’s all sorts of stuff and there’s no way of seeing it all.”

To be able to see such minuscule components through a microscope, scientists find naturally occurring or engineered fluorescent proteins that glow when certain wavelengths of light are focused on them.

With the CRISPR-Cas 9 gene editing technique, Hallam modified the genome of human cells, creating a fluorescent protein and connecting it to a key component within gamma secretase called nicastrin.

He used a state-of-the-art spinning disc confocal fluorescence microscope, housed in the Brock-Niagara Validation, Prototyping and Manufacturing Institute to do so.

“No one has ever done this before,” says Necakov. “This has allowed us to study the dynamics and localization of the gamma secretase enzyme in living cells at high resolution in order to better understand how this key enzyme does its job.”

Hallam is also wrapping up another study — under the direction of Associate Professor of Health Sciences Rebecca MacPherson — examining how and why a protein called brain derived neurotrophic factor (BDNF) reduces the amount of amyloid beta being produced in the brain.

Previous research in the field and from the MacPherson Lab has shown exercise stimulates the production of BDNF.

Hallam, who is defending his PhD dissertation in July and then heading to the Robarts Research Institute in London, Ont., credits his success to the training and support he received from Necakov.

“I don’t think I would have pursued research or even went to graduate school if it wasn’t for Dr. Necakov,” says Hallam. “He encouraged me to be curious, come up with my own ideas and figure out how I would approach studying them, which prepared me to be a strong scientist.”