Building mini-brains to understand the LRRK2 protein

Although researchers have pinpointed defective versions of the LRRK2 gene as the cause of a familial form of Parkinson’s disease, they don’t know exactly what function the protein that the gene expresses plays in damaging brain cells.

At Montreal’s Neurological Institute, Emma MacDougall, a PhD student at McGill University, is investigating what the LRRK2 protein does.

High levels of LRRK2 are found in in microglial brain cells. The protein’s presence indicates it may play a role in clearing away debris from damaged brain cells, MacDougall says – but she doesn’t know exactly how.

To find out, she’s using a novel tool called human-induced pluripotent stem cells.

MacDougall will use blood and skin samples from people with Parkinson’s disease to produce these stem cells, which she’ll then transform into microglial brain cells.

“This really allows us to mimic the human body in a way we’ve never been able to before, so we can really study these proteins in an environment most closely connected to an environment we could see in the human body.”

By growing these brain cells as 3D models, MacDougall will create what’s called a neural organoid – or a “mini-brain.” These mini-brains are 3D pieces of tissue composed of all the different cells in the human brain.

MacDougall will then compare the mini-brains from people with Parkinson’s disease to mini-brains she creates using stem cells from healthy people. She’ll observe the way the LRRK2 protein alters the behavior of the cells in each model.

“This really allows us to mimic the human body in a way we’ve never been able to before, so we can really study these proteins in an environment most closely connected to an environment we could see in the human body,” she says.

By understanding LRRK2’s function, MacDougall hopes to better understand the process that causes Parkinson’s and develop new drug targets to prevent the disease’s progression.

MacDougall’s interest in how the brain and the body work together to create movement was sparked by her experience as a ballet dancer. High school science classes where she learned how to trace a disease back to a change in a base pair of DNA cemented her interest in research on the genetic components of disease.

She hopes her work with LRRK2 will lead to a potential treatment for both inherited forms of Parkinson’s and sporadic types of the disease.

Working in the Montreal Neurological Institute, MacDougall encounters people who could benefit from her research.

“Every day you can see the people you are working towards helping in the future, so that’s quite inspiring.”