Unmasking molecular culprits in Parkinson’s disease
Investigating molecular regulators of PINK1 levels
Mohamed Eldeeb’s curiosity about the behaviour of cancer cells led him to seek similar insights into the way brain cells respond to Parkinson’s disease. As a doctoral student at the University of Alberta, he was intrigued by how cancer cells mounted a resistance to chemotherapy and began to explore the mechanisms that enabled these cells to fend off these powerful drugs. Now at McGill University as a postdoctoral researcher, he is exploring why brain cells find themselves unable to resist the process of neurodegeneration.
“My model is that a major factor in modulating cell death is the regulation of the levels of some proteins,” he explains. “This regulation of protein levels matters in determining the cell’s state—whether it will succumb to death or recover.”
Eldeeb is examining the molecular regulators of one particular protein, known as PINK1, which oversees the activity of the mitochondrion, a critical component of almost every cell in the body. Mitochondria are responsible for generating the energy cells use to carry out their respective functions. In Parkinson’s, a systematic breakdown of mitochondria in brain cells reduces the production of dopamine, the chemical that’s crucial for sending signals from the brain to muscles.
Eldeeb uses the advanced genome-editing tool CRISPR to manipulate different proteins linked to PINK1. This process will help him identify the particular molecules involved in regulating this gene, but it generates considerable amounts of information, which calls for sophisticated computer hardware and software that will seek out meaningful patterns from this mass of data.
“Our project will bridge gaps in the cellular basis underlying the development of Parkinson’s,” he says. This type of disease modelling may lead to new directions for drugs and therapies.
“The cell lines and findings generated by this project will provide a useful resource for the Parkinson’s community by identifying possible targets that could be used to halt the progression of this condition.”