Connecting Minds
Pioneering New Frontiers in Brain Health Research.
Prof. Minh Dang Nguyen believes in exploring areas of research where few others go.
“I like to ask questions that nobody asks. And if you ask the right question, then you get answers that nobody expects,” said the professor of clinical neuroscience at the University of Calgary.
“It’s a risky type of science sometimes, and I would say most of the time it’s not funded. But that’s what attracts me.”
The same is true of his latest research project, in which he hopes to push the boundaries of our knowledge of the brain and the devastating disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. And it is funded, thanks to a new pilot program from Brain Canada, Weizmann Canada, and the Weizmann Institute of Science, an initiative that aspires to encourage open science.
“We’re very grateful for (the grant) because the research is out of the box. You wouldn’t be able to get funding from a traditional funding agency,” Prof. Nguyen said in an interview with Mind Over Matter®.
The project is a collaboration with Prof. Eran Elinav of the Weizmann Institute in Israel. They are studying links between the brain and the microbiome – the vast array of bacteria, viruses, and fungi in the gut.
“The project is significant because it addresses a devastating neurodegenerative disorder that has no cure, ALS, and aims to decode the roots of microbiome regulation of this disease,” said Prof. Elinav.
Previous research from the Elinav Lab has indicated that gut bacteria can have an impact on ALS, either slowing down or accelerating the progress of the disease. This project will get more specific, exploring whether alterations in the microbiome can affect what is known as the glymphatic system, a newly discovered system that acts to clear waste from the central nervous system.
Using mouse models, the researchers are investigating whether promoting healthy gut bacteria can make the glymphatic system more effective in clearing waste from the brain and, in the process, slow the progression of ALS.
EXPLORING SEX DIFFERENCE IS A KEY ELEMENT OF THE PROJECT. MEN TEND TO GET ALS MORE COMMONLY THAN WOMEN.
The researchers will observe how manipulating the microbiome affects male and female mice differently.
“And hopefully, we want to eventually come up with a strategy to slow down Alzheimer’s. It’s very exciting because you can modify the microbiome depending on how you eat and sleep,” said Prof. Nguyen.
“Results obtained from this study will be harnessed toward future testing in human patients,” added Prof. Elinav.
Theirs is one of three projects to be awarded a Brain Canada and Weizmann Institute of Science Team grant. In each case the goal is not only to support exploratory science, but to foster collaboration among researchers with complementary capabilities from different parts of the world.
AS WITH OTHER ‘HIGH-RISK, HIGH-GAIN’ PROJECTS, FUNDING VIA ‘TRADITIONAL’ SOURCES IS OFTEN MET WITH CHALLENGES.
“The opportunity generously provided here will enable the ongoing Canadian-Israeli collaboration to move even faster in achieving the project’s scientific and medical goals to the benefit of humanity,” continued Prof. Elinav.
BRAIN DEFENCE
“The beauty of this initiative is the ability to bring groups from different disciplines and put them together to make the impossible possible,” said grant recipient Prof. Ido Amit of the Weizmann Institute.
He and Prof. Nahum Sonenberg of McGill University are exploring how the brain’s immune system could be harnessed to fight Alzheimer’s disease (AD), based on a growing body of recent evidence that found a strong connection between the immune system and AD, the most common form of dementia.
They are employing cutting-edge genomic and artificial intelligence technologies to measure and manipulate the mRNA translation machinery to modify immune cells called microglia at the genetic level. Using lab mice, they will see if they can make the microglia more effective in warding off amyloid plaques, which are proteins found in the brain that are associated with AD.
“What’s beautiful about activating our own immune system is that it can bring back brain function, without causing damage. This could be the Holy Grail of genetic diseases, and Alzheimer’s specifically,” Prof. Amit told Mind Over Matter® in an interview from his office at the Weizmann Institute in Israel.
“If we can reactivate the broken resident immune system in the brain, it will make a huge impact on the mental health and general quality of life of patients who suffer from a whole suite of neurodegenerative diseases, including Alzheimer’s.”
We’re hoping to make a breakthrough that will be relevant for both women and men. But for women, it will be even more important, given the higher frequency of the disease.
Prof. Sonenberg said that using both male and female lab mice will allow their research to contribute to a more complete understanding of the factors associated with AD. “If we have the full picture, we’ll have a better idea how to combat the disease,” he told Mind Over Matter®.
IMPROVING PRECISION
A greater understanding of the causes of depression is the goal of the third funded project, which is a collaboration between Prof. Ilan Lampl of the Weizmann Institute and Dr. Etay Hay of the Centre for Addiction and Mental Health (CAMH) in Toronto. They are focusing on particular brain cells called somatostatin (SST) interneurons. Autopsies of people who suffered from major depression showed lower levels of SST expression in these cells. The researchers are exploring whether there is a direct link.
“We want to achieve specificity. We want to know if these cells alone can affect depression,” said Prof. Lampl.
Using a technique called optogenetics and a mouse model of depression, the team will shine a light on the SST interneurons of mice that have a form of depression and investigate whether this stimulation recovers brain activity to levels seen in non-depressed mice. They will use equal numbers of male and female mice so that they can note any differences between the sexes.
“This will really establish whether that mechanism is relevant for depression, and it will offer insights that could help guide us on what kind of activation or treatment protocols would be effective,” Dr. Hay told Mind Over Matter®.
The researchers anticipate that their work could pave the way for future projects that develop treatment protocols using new drugs that treat depression with more precision.
“It’s important because the current medications for depression are not specific – they are acting on many cells in different brain regions and therefore have many side effects,” said Prof. Lampl.
Recipients applauded the Brain Canada and Weizmann Institute of Science Team Grants program for fostering international collaboration, and for funding projects that otherwise might have difficulty securing support.
“It’s a very generous grant, and it’s accepting risky projects. It would be hard to fund that kind of project quickly through more conservative channels,” said Dr. Hay.
WORKING TOGETHER TO BOOST BRAIN HEALTH
“The selection of these remarkable teams, through our rigorous, independent peer review process, exemplifies the power of international collaboration in advancing our knowledge of the brain,” said Dr. Viviane Poupon, President and CEO of Brain Canada.
BY UNITING DIVERSE EXPERTISE AND PERSPECTIVES, THESE PROJECTS ARE WELL-POSITIONED TO MAKE STRIDES IN UNRAVELLING THE COMPLEXITIES OF THE BRAIN.
This program is made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada) and Brain Canada, and Weizmann Canada.
Susan Stern, CEO of Weizmann Canada, is equally enthusiastic about the grant program.
“With this project there is much to celebrate – the high calibre of the neuroscience research being undertaken, its focus on critical areas of brain health that require exploration, and in particular, its collaborative framework. Our Canadian donors give with intent, knowing that the Weizmann Institute of Science partners with the world’s best because sharing ideas and expertise strengthens science and innovation for the benefit of all people,” she said.
Ms. Stern and Dr. Poupon highlighted the vision of the donors who made the program possible, notably Dr. Daniel C. Andreae and the Larry and Judy Tanenbaum Family Foundation, who played pivotal roles in bringing this pilot program for scientific research to fruition.
Larry Tanenbaum is Vice-Chair at Brain Canada and Founder of the Tanenbaum Open Science Institute (TOSI) at the Neuro (Montreal Neurological Institute-Hospital).
Their support expands the possibilities for brain health and collaborative research.
Source: Mind Over Matter V20