University of Regina research team makes significant discovery into a rare disease

By Krista Baliko Posted: October 1, 2019 5:00 a.m.

University of Regina researchers who contributed to a recently published paper in the journal iScinece. (l to r) Dr. Shahreen Amin, MD and PhD student; Larissa Hoell, research associate; Dr. Mohan Babu, associate professor; Dr. Mara Zilocchi, postdoctoral fellow; Dr. Mohamed Taha Moutaoufik, postdoctoral fellow; Dr. Hiroyuki Aoki, senior research associate. Missing from the photo are Dr. Ramy Malty, postdoctoral fellow, and PhD student Qingzhou Zhang.
University of Regina researchers who contributed to a recently published paper in the journal iScinece. (l to r) Dr. Shahreen Amin, MD and PhD student; Larissa Hoell, research associate; Dr. Mohan Babu, associate professor; Dr. Mara Zilocchi, postdoctoral fellow; Dr. Mohamed Taha Moutaoufik, postdoctoral fellow; Dr. Hiroyuki Aoki, senior research associate. Missing from the photo are Dr. Ramy Malty, postdoctoral fellow, and PhD student Qingzhou Zhang. Photos: U of R Photography

According to the World Health Organization rare diseases are often serious, chronic, and life threatening. In Canada, about one in twelve people are affected by a rare disease. Most are caused by gene mutations, including those in mitochondria, which are what generate energy in our cells to keep our bodies functioning. And a mutation in the mitochondrial gene can contribute to rare disorders.

One example of a rare metabolic disorder is human mitochondrial respiratory chain deficiency. Now, a University of Regina-led research team, which includes postdoctoral fellows and graduate students, and collaborators from the University of Saskatchewan, Japan, and Italy, has made a major discovery that will bring them one step closer to understanding this disease.

_URP9026-new-5x7-photo-2.jpg

Dr. Moutaoufik, a postdoctoral
fellow in the Department of
Biochemistry and one of the
co-lead authors of the research
team’s recently published
paper, in a University of Regina lab.

_URP9042-new-5x7-photo-3.jpg

Larissa Hoell, a research
associate in the Department
of Biochemistry and a co-author
of the research team’s
recently published paper,
in a University of Regina lab.

“Our research team has discovered a new function for a previously unknown gene,” says Dr. Mohan Babu, a biochemist at the University of Regina who is leading the team that made the find. “We renamed this unknown – or orphan – mitochondrial gene RCAF1 – which stands for respirasome complex assembly factor 1, because this particular gene has a significant role in respiration that is required for our energy balance.”

Babu says his team sequenced close to 300 samples from Japanese patients with respiratory chain deficiencies, and in 16 of the 300 people the researchers discovered a very rare variant – or mutation – in a particular gene that previously had an unknown function. The mutation resulted in the gene having a reduced level of mitochondrial respiration.

Using samples from Italian patients with the respiratory chain deficiency gene mutation, Babu says the scientists then conducted several reversal experiments.

“We used CRISPR technology (a powerful tool that allows researchers to edit or alter genes) to reverse the respiration defect from patients with respiratory chain deficiency,” explains Babu. “We added the correct gene sequence back into the mutated gene of the respiratory chain deficient patients and found that respiration levels were restored. This means that the particular mutation we discovered plays a major role in rare respiratory chain deficiency metabolic disorder.”

Babu says the team’s next step is finding out what mechanism behind the mutation is contributing to respiratory chain deficiency. This new knowledge will allow researchers like Babu and his team to better understand this rare metabolic disorder.

“These types of rare metabolic disorders affect our brain, liver, tissues, and muscles, yet we don’t know how gene mutations will manifest. But we are in a race to find out, because rare diseases are becoming more common,” says Babu.

He says that while right now the team has found respiratory chain deficiency in patient samples from Italy and Japan, they also have evidence that supports it exists in Canada, too.

The Canadian Organization for Rare Disorders reports that there are currently more than 7,000 rare diseases that we know about, with more being discovered each year.

“There is so much about rare diseases and disorders that scientists and doctors don’t know, but we do know that research into them is imperative for human health.”
The research team’s findings were recently published in the journal iScience.


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