Parkinson's

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle — Tue, 20 Aug 2024 16:17:45 +0000

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle Tue, 08/20/2024 - 12:17

Cutline

The "SynNeurGe" classification system for Parkinson's disease, proposed by researchers led by Professor Anthony Lang of the University Health Network and ��˾��ֱ��, is based on three key biomarkers (photo by FG Trade/Getty Images)

Eileen Hoftyzer

Topic

Breaking Research

Department of Medicine

Temerty Faculty of Medicine

Tanz Centre for Research in Neurodegenerative Diseases

Parkinson's

University Health Network

Subheadline

The classification system could enable advancements in the development of tailored treatments for Parkinson's disease

A team of researchers led by Anthony Lang of the University Health Network and the University of Toronto have proposed a novel classification system for Parkinson’s disease that considers biological features and not just clinical symptoms.

The "SynNeurGe" system, described by Lang and collaborators in a paper published in The Lancet Neurology, classifies Parkinson’s disease based on three biomarkers: presence or absence of misfolded alpha synuclein protein, which is believed to cause or contribute to the underlying neurodegeneration; evidence of neurodegeneration using imaging techniques; and presence of gene variants that increase disease risk.

The researchers argue that such a classification system is necessary to advance the development of tailored treatments for Parkinson’s disease.

Professor Anthony Lang (supplied image)

“This is a complex group of disorders that may cause similar symptoms, but biologically they're very different,” says Lang, a senior scientist and Lily Safra Chair in Movement Disorders at UHN and a professor in the department of medicine and the Tanz Centre for Research in Neurodegenerative Disease at ��˾��ֱ��’s Temerty Faculty of Medicine, where he holds the Jack Clark Chair for Parkinson’s Disease Research

“If we cannot find ways to subdivide patients biologically, then applying a therapy designed to affect one biological pathway may not be effective in another group of patients that doesn't have that same pathway involved – and we won’t really have precision or personalized medicine for Parkinson’s disease.”

Currently, Parkinson’s disease is classified based on clinical presentation and symptoms, but the disease can affect the brain for years, possibly even decades, before symptoms appear. For future therapies to treat the underlying disease rather than just the symptoms, patients will need early intervention and treatments tailored to the biological features of the disease, researchers say.

Similar approaches are being used for other diseases – cancer treatments vary not only by the location of tumors but also their molecular features, and the development of drugs for Alzheimer’s disease is increasingly guided by the specific biological mechanisms involved in the disease.

The SynNeurGe classification system, while based on the three key biomarkers, also considers whether clinical features are present. The different combinations of biomarkers classify the disease into various sub-types.

Lang and co-authors note that such a classification should only be used for research at present, although it will almost certainly have clinical applications.

“Eventually we will see a biological approach influencing clinical care, particularly when we finally have effective disease-modifying therapies,” says Lang. “We currently don’t know how important these biomarkers actually are.

"We need large-scale prospective studies of biomarkers, imaging and clinical features to interpret the results, give patients accurate information about their diagnosis and provide appropriate treatment.”

Lang’s team plans to start conducting such studies of cerebrospinal fluid, skin and blood to look for biomarkers of different sub-types of Parkinson’s disease that will help inform the classification system and the development of tailored therapies.

“Now is the time to think about these diseases not solely based on their clinical manifestations, but to look at the biology and try to separate different biological subtypes so we can ultimately improve treatment for this disease,” Lang says.

Professor Graham Collingridge, director of the Tanz Centre, says Lang and his team’s “landmark paper” is poised to have a significant impact on clinical practice around Parkinson's. “I am delighted that our researchers have played such a key role in this important biological classification,” Collingridge says.

Lang says research by Tanz Centre scholars has contributed significantly to the body of knowledge used to develop the proposed biological classification.

For example, Professor Ekaterina Rogaeva’s research on the genetics and epigenetics of Parkinson’s disease has shown that multiple genes and environments can influence Parkinson’s risk, highlighting the need to tailor therapies based on a patient’s genetic makeup.

Other researchers – including Anurag Tandon, Joel Watts, Martin Ingelsson and Gabor Kovacs – have been studying the role of misfolded alpha synuclein in neurodegeneration as well as cases of Parkinson’s disease where alpha synuclein is absent – which informed how Lang’s team included the protein in the classification.

��˾��ֱ�� researchers' approach to producing neural cells could yield new treatments for Parkinson’s

rahul.kalvapalle — Mon, 13 May 2024 13:03:19 +0000

��˾��ֱ�� researchers' approach to producing neural cells could yield new treatments for Parkinson’s

rahul.kalvapalle Mon, 05/13/2024 - 09:03

Cutline

PhD Student Andy Yang, left, and Professor Stephane Angers, right, at the Donnelly Centre for Cellular and Molecular Biology are advancing a novel approach to developing dopaminergic neurons (supplied images)

Anika Hazra

Topic

Breaking Research

Institutional Strategic Initiatives

Temerty Faculty of Medicine

Donnelly Centre for Cellular & Biomolecular Research

Graduate Students

Leslie Dan Faculty of Pharmacy

Medicine by Design

Parkinson's

Research & Innovation

Subheadline

An antibody was used to selectively activate a receptor in a molecular signalling pathway to develop dopaminergic neurons

Researchers at the University of Toronto believe they’ve found a way to better control the generation of key neurons depleted in Parkinson’s disease – suggesting a potentially new approach to addressing a disease with no cure and few effective treatments.

In preclinical studies, the researchers used an antibody to selectively activate a receptor in a molecular signalling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter critical to brain health.

While researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons to replace those lost in patients living with Parkinson’s disease, the efforts have so far been hindered in part by an inability to target specific receptors and areas of the brain.

“We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway,” said principal investigator Stephane Angers, who is director of ��˾��ֱ��’s Donnelly Centre for Cellular and Molecular Biology and a professor in the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine.

“We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway. This activation method has not been explored before.”

Parkinson’s disease is the second-most common neurological disorder after Alzheimer’s, affecting over 100,000 Canadians. It particularly impacts older men, progressively impairing movement and causing pain as well as sleep and mental health issues.

Most previous research efforts to activate the Wnt signaling pathway relied on a GSK3 enzyme inhibitor. This method involves multiple signaling pathways for stem cell proliferation and differentiation, which can have an unintended effect on the newly produced neurons and activate off-target cells.

“We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain,” said Andy Yang, first author on the study and a PhD student at the Donnelly Centre. “Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin.”

Another promising finding of the study, published recently in the journal Development, is that implanting the artificially-produced neurons in a rodent model with Parkinson’s disease led to improvement of the rodent’s locomotive impairment.

“Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3,” said Yang. “These experiments will confirm which method is more effective in improving symptoms of Parkinson’s disease ahead of clinical trials.”

The research was supported by ��˾��ֱ��’s Medicine by Design program, an institutional strategic initiative that receives funding from the Canada First Research Excellence Fund and the Canadian Institutes of Health Research.

Researchers identify a potential new therapeutic target in Parkinson’s disease

siddiq22 — Mon, 24 Apr 2023 13:50:47 +0000

Researchers identify a potential new therapeutic target in Parkinson’s disease

siddiq22 Mon, 04/24/2023 - 09:50

Cutline

A new study by researchers from UHN and ��˾��ֱ�� examined how to prevent the accumulation in the brain of a protein that contributes to Parkinson's disease (photo by Christian Wiediger via Unsplash)

Topic

Breaking Research

Temerty Faculty of Medicine

Tanz Centre for Research in Neurodegenerative Diseases

Donnelly Centre for Cellular & Biomolecular Research

Medical Research

Neurology

Parkinson's

University Health Network

A team of researchers from the Krembil Brain Institute (KBI) and the University of Toronto have identified a protein-protein interaction that contributes to Parkinson’s disease.

In a study published in Nature Communications, KBI scientists Lorraine Kalia and Suneil Kalia and ��˾��ֱ�� researcher Philip M. Kim examined a protein called alpha-synuclein (a-syn) that accumulates in the brain in patients with Parkinson's and leads to cell death.

Much research is currently focused on clearing a-syn with antibodies or using small molecules to prevent a-syn from aggregating. In their study, the researchers took an alternate approach by looking for protein-protein interactions that may be promoting the accumulation of a-syn in Parkinson’s disease.

Protein-protein interactions govern most inner workings of the cell, including breaking down disease-causing proteins. Inhibiting certain interactions has emerged as a promising approach to treat diseases such as stroke and cancer.

“Identifying a particular interaction that contributes to a disease, and then finding ways to disrupt it, can be a painstaking and incredibly slow process,” says Lorraine Kalia, who is also a staff neurologist at University Health Network, a scientist at ��˾��ֱ��’s Tanz Centre for Research in Neurodegenerative Diseases and an assistant professor in the division of neurology and in the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine.

“We all started out a bit skeptical that we would have something useful at the end, and so the fact that we do have something that warrants further work is much more than we anticipated.”

Kim, who is a professor in ��˾��ֱ��’s Donnelly Centre for Cellular and Biomolecular Research and in the department of molecular genetics in the Temerty Faculty of Medicine, notes the team took an approach they hoped would expedite the discovery of potential therapies.

“We developed a platform to screen molecules called peptide motifs – short strings of amino acids that can disrupt protein-protein interactions – for their ability to protect cells from a-syn,” Kim says. “Once we identified candidate peptides, we determined which protein-protein interactions they target.”

Through this approach, the team identified a peptide that reduced a-syn levels in cells by disrupting the interaction between a-syn and a protein subunit of the cellular machinery called “endosomal sorting complex required for transport III” (ESCRT-III).

“ESCRT-III is a component of a pathway that cells use to break down proteins, called the endolysosomal pathway. We discovered that a-syn interacts with a protein within ESCRT-III – CHMP2B – to inhibit this pathway, thereby preventing its own destruction,” Lorraine Kalia says.

“We were impressed that the platform worked. But I think what was more interesting is that by doing this kind of screening, we were able to find an interaction that was really not previously characterized, and we also found a pathway that’s not yet been targeted for therapeutics.”

Once the group identified this interaction, they confirmed that they could use their peptide to disrupt it – preventing a-syn from evading the cell’s natural clearance pathways, notes Suneil Kalia, who holds the R.R. Tasker Chair in Stereotactic and Functional Neurosurgery at UHN and is an associate professor in the division of neurosurgery in the Temerty Faculty of Medicine.

“We tested the peptide in multiple experimental models of Parkinson’s disease, and we consistently found that it restored endolysosomal function, promoted a-syn clearance and prevented cell death,” he says.

These findings indicate that the a-syn-CHMP2B interaction is a potential therapeutic target for the disease, as well as other conditions that involve a buildup of a-syn, such as dementia with Lewy bodies (another disease associated with abnormal deposits of a-syn in the brain).

The next steps for this research are to clarify exactly how a-syn and CHMP2B interact to disrupt endolysosomal activity. Ongoing studies are also determining the best approach for delivering potential therapeutics to the brain.

“This research is still in its early stages – more work is definitely needed to translate this peptide into a viable therapeutic,” cautions Lorraine Kalia. “Nonetheless, our findings are very exciting because they suggest a new avenue for developing treatments for Parkinson’s disease and other neurodegenerative conditions.”

This study also highlights the value of multidisciplinary collaborations in health research.

“We simply could not have conducted this study in a silo. The endolysosomal pathway is underexplored, so it was not an obvious place to look for potential disease-related protein-protein interactions. Dr. Kim’s screening platform was critical for pointing us in the right direction,” Suneil Kalia points out.

“It is really extraordinary to see this platform – which we initially used to find potential therapeutics for cancer – yielding advances in brain research. The pathways that cells use to stay healthy are fundamentally very similar across tissues, so the insights that we gain about one organ system or disease could have important implications in other contexts,” Kim says.

“It’s really brand-new science and targets that haven’t been a focus for drug development for Parkinson’s," Lorraine Kalia adds. "We hope this changes the landscape for treatment of this disease, which is so in need of new therapies.”

The research was supported by the Canadian Institutes of Health Research, the Michael J. Fox Foundation for Parkinson’s Research, Parkinson’s UK, the Canada Foundation for Innovation, the Ontario Research Fund, the Krembil Research Institute and the UHN Foundation.

This story was originally published on the website of the Krembil Brain Institute, University Health Network.

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Neurodegenerative Diseases

Biomolecular Research

��˾��ֱ�� startups win prizes for products helping disabled, injured

Christopher.Sorensen — Wed, 17 May 2017 19:50:36 +0000

��˾��ֱ�� startups win prizes for products helping disabled, injured

Christopher.Sorensen Wed, 05/17/2017 - 15:50

Cutline

Emile Maamary and Mark Elias show off Steadiwear's tremor-dampening glove and the startup's latest award (photo by Chris Sorensen)

Chris Sorensen

Author legacy

Chris Sorensen

Topic

Subheadline

Steadiwear produces a tremor reducing glove. MyndTec has an electrical stimulation device to help patients with strokes or spinal cord injuries

Watching an elderly loved one struggle with a disability is never easy. But while most of us simply grimace and soldier on, Mark Elias decided to do something about it.

The co-founder of Steadiwear, a University of Toronto startup, developed a specially designed glove that stabilizes the hands of patients with Parkinson’s disease or essential tremor.

This week, Steadiwear was one of two ��˾��ֱ�� startups to win competitions at the Ontario Centres of Excellence Discovery conference, an event that seeks to promote the commercialization of innovative ideas in the province. The other startup was MyndTec Systems, which won an accessibility-tech pitch competition with an electrical stimulation system that helps patients with upper-limb paralysis regain movement.

Elias got the idea for Steadiwear after visiting his grandmother in France several years ago.

“I saw her spilling coffee on herself helplessly, and it was very painful for me,” said Elias, who graduated from ��˾��ֱ�� three years ago with a bachelor’s degree in applied science and civil engineering. “When I returned to Toronto, I made it my personal mission to solve this problem.”

His solution? Elias started by investigating the tuned dampening systems used to make buildings more earthquake resistant. He eventually settled on a ball joint surrounded by a non-Newtonian fluid – not unlike the state-shifting slurry one gets by mixing cornstarch with water. The resulting device, developed with co-founder Emile Maamary at ��˾��ֱ��’s Impact Centre accelerator, allows patients to move their hands voluntarily but stiffens up when it encounters the quick, jerky movements associated with tremors.

That's in stark contrast to existing tremor treatments that either rely on powerful drugs, which can have unpleasant side effects, or weighted gloves that impede voluntary movement and cause muscle strain.

On Tuesday, Elias and Maamary won the Ontario Brain Institute’s ONtrepreneurs $20,000 Pitch Challenge – the fourth award Steadiwear has won in the past few months.

Steadiwear's growing pile of hardware shouldn't come as a suprise. Canada's aging population – the number of seniors recently surpassed the number of children in Canada for the first time – means there is ballooning demand for new innovative products to help elderly Canadians live more comfortably with chronic diseases and disabilities.

It also happens to be an area where ��˾��ֱ�� entrepreneurs and researchers are carving out an area of expertise, building on research done at ��˾��ֱ�� and partner hospitals.

��˾��ֱ�� startups, many of them focused on the accessibilty space, put in a particularly strong showing at the ONtrepreneurs pitch competition. All but one of the five finalists were from the university, which boasts 10 accelerators spread across its three Toronto-area campuses.

The others were: WinterLight Labs, which developed a system to assess dementia based on patients’ speech; iMerciv, which makes a wearable device to assist people with vision loss; and SensOR Medical Laboratories, which devised a force-sensing skin tool to help students and surgical residents improve performance when using minimally invasive surgical techniques.

Professor Milos Popovic (left) and his team give a demonstration of MyndMove, MyndTec Inc.’s first commercial product (Photo: Barry Westhead / Toronto Rehabilitation Institute)

The other big ��˾��ֱ�� winner at OCE Discovery was MyndTec, co-founded by Milos Popovic, a professor at ��˾��ֱ��’s Institute of Biomaterials & Biomedical Engineering and a senior scientist at Toronto Rehab, and Aleksandar Prodic, a professor at the university’s department of electrical and computer engineering.

MyndTec’s first commercial product, MyndMove, uses a system of coordinated electrodes to stimulate arm muscles and replicate functional upper limb movement in patients who have suffered strokes or spinal cord injuries. Here’s how it works in practice: a physiotherapist will tell a patient to think about executing a movement – making a fist, for example – and MyndTec’s system will stimulate the patient’s arm into action.

“Eventually those will connect and create a new pathway from an uninjured part of the brain,” says Alexa Granger, a quality assurance manager at MyndTec. “If someone’s had a stroke or spinal cord injury, and they now have paralysis or weakness in the arm and hand, they can’t do many things that we take for granted – like bathing ourselves, feeding ourselves, grooming ourselves, getting dressed. With our therapy, we can help them to gain some function back in their arms and hands.”

MyndTec's equipment is already available at clinics in Ontario and B.C.. The company is now preparing to launch into the huge U.S. market.

Reza Moridi, Ontario’s minister of research, innovation and science, congratulated MyndTec and the accessibility competition’s other finalists, which included TranQool – a startup founded by ��˾��ֱ�� alumni that uses encrypted video to match users with cognitive behavioural therapists.

“These talented innovators are making a real difference for people with disabilities, and for Ontario,” Moridi said.

Learn more about Entrepreneurship at ��˾��ֱ��

��˾��ֱ�� researcher launches startup to help find new smart drugs

ullahnor — Mon, 24 Apr 2017 17:03:11 +0000

��˾��ֱ�� researcher launches startup to help find new smart drugs

ullahnor Mon, 04/24/2017 - 13:03

Cutline

Professor Igor Stagljar's new startup ProteinNetwork Therapeutix will be based in Toronto

Chris Sorensen

Author legacy

Chris Sorensen

Topic

Subheadline

The lab’s technology maps cell membrane protein interactions for hundreds of diseases like cancer, Parkinson’s, Alzheimer’s, diabetes and cardiovascular disease

Igor Stagljar likens the process of commercializing his ground-breaking research into cell membrane proteins – which has yielded hundreds of new targets for drug-makers seeking cures for cancer and other deadly diseases – to building a highly automated Tesla factory.

But there’s a key difference: ProteinNetwork Therapeutix will be based here in Canada, not south of the border.

Stagljar, a professor of biochemistry and molecular genetics at the University of Toronto, initially considered setting up his new venture in Silicon Valley. But he and business partner Ivan Plavec ultimately decided Toronto was a better option.

“The technology is here and the know-how is here,” says Stagljar, citing ��˾��ֱ��’s large pool of research talent and a growing cluster of venture capital investors on or near the university’s downtown campus. “Maybe some people from my lab will even go to work for the company.”

Read about his latest research findings for Parkinson's

Helping to seal the deal: a $1 million grant from CQDM’s Quantum Leap program. The grant, co-funded by the Brain Canada Foundation, targets research with “very high potential impact” within the biopharmaceutical industry. It’s only the second time the program has funded a Canadian researcher. The other was ��˾��ֱ��’s Andrei Yudin, a professor of chemistry.

Stagljar’s research certainly qualifies as having a potentially big commercial impact.

With the help of his 17-person lab, he developed a new genetic technique that allows researchers to map the interactions between proteins in a cell’s membrane, a process previously made difficult because of the proteins’ fragile, transitory states. The interactions play a key role in determining whether a cell stays healthy or becomes diseased, and are therefore of huge interest to pharmaceutical companies seeking a new generation of precision drugs to cure deadly diseases like cancer.

“There’s about 500 proteins that we know of nested in the cellular membranes that are involved in the onset of various human diseases,” says Stagljar, citing cancer, Parkinson’s, Alzheimer’s, hypertension, diabetes, cardiovascular disease and even migraines. “There are approximately 500 diseases that can be tackled with this technology.”

But studying protein interactions in the lab is not the same as systematically evaluating them on a commercial scale. So Stagljar is in the process of retooling his laboratory at ��˾��ֱ��’s Donnelly Centre for Cellular Biomolecular research, tapping a local Ontario company to design and build robotics that can handle hundreds of screens per day.

Everything should be up and running within the next 12 months. Stagljar’s focus at ��˾��ֱ�� will be on “druggable” membrane proteins related to three types of cancer: lung, breast and pancreatic. His company, meanwhile, will use similar technology and equipment to focus on other diseases in partnership with pharmaceutical partners.

“We’re already leading very serious talks with well-known drug companies,” Stagljar says. “Two out of the five biggest pharmaceutical companies are interested in our technology.”

How long until ProteinNetwork expects to see results?

“I think in the next two or three years, we will learn about new drug targets, which, when neutralized by drugs, would lead to cures for these cancers,” says Stagljar. “But before these drugs would appear in clinics is a long process, from nine to 12 years.

“Our focus right now is to build a high-throughput, high-grade technology for biomedical research.”

Learn more about entrepreneurships and startups at ��˾��ֱ��

��˾��ֱ�� study provides new hope for Parkinson’s as elusive proteins come to light

ullahnor — Thu, 16 Mar 2017 18:01:08 +0000

��˾��ֱ�� study provides new hope for Parkinson’s as elusive proteins come to light

ullahnor Thu, 03/16/2017 - 14:01

Cutline

Research reveals a breadth of new drug targets for neurological conditions and opens the door to a greater understanding of the way in which common medications work

Jovana Drinjakovic

Author legacy

Jovana Drinjakovic

Topic

Ever take antihistamines? Or heartburn medication?

Along with drugs used for a variety of conditions like diabetes, high blood pressure and depression, these common household drugs work by targeting the same class of protein molecules in our cells. They are only the tip of the iceberg. A University of Toronto study reveals a large swath of new therapeutic opportunities for these drugs, including ones that could lead to a better treatment for Parkinson’s disease.

Despite representing about a half of prescribed medications worldwide, these compounds target only a sliver of one of the largest – and most elusive – classes of human proteins, called G protein coupled receptors (GPCRs). Tapping into this vast unexplored therapeutic potential has been difficult because available tools weren’t up to the task of surveying the GPCRs on a large scale.

Enter Professor Igor Stagljar of ��˾��ֱ��’s Donnelly Centre.

“Our cells are made of proteins, which also do most of the work in them. But no protein acts alone and that’s why we have to look at interactions between proteins to understand what’s going on in the cell,” says Stagljar, who is also a professor in the departments of molecular genetics and biochemistry.

Stagljar’s new study, which is on the cover of the March issue of Molecular Systems Biology, is based on technology developed in his lab, called MYTH.

The technology allows detection of membrane protein interactions as they occur in their natural setting – on the surface of cells. Using MYTH, Stagljar’s team was able to capture almost 1,000 interactions between more than 600 proteins for almost 50 clinically important GPCRs (see inset).

The largest survey of GPCRs to date, it revealed new associations among proteins involved in neurological disorders like motor neuron disease, schizophrenia and neurodegenerative disorders, as potential targets for new drugs.

One association that stood out involved a G protein coupled receptor targeted by Parkinson’s disease drugs, called ADORA2A. By binding to ADORA2A, the drugs stimulated the release of dopamine, which helped communication between nerve cells to ultimately reduce tremor in patients with Parkinson’s.

Stagljar’s team found that ADORA2A associates with another Parkinson’s disease associated receptor (GPR37), in a way that affects movement in a mouse model of disease, suggesting that a combination of drugs targeting both receptors may work better in patients.

The work on Parkinson’s was done in collaboration with Professor Francisco Ciruela’s team at the University of Barcelona in Spain, which will continue to investigate the clinical potential of the enhanced combination therapy involving ADORA2A and GPR37.

“High-throughput studies like ours are going to be major contributors in future drug development,” says Jamie Snider, a senior research associate in the lab and a lead author of the study. “You can look at the cell in the ways we could not do before. We can understand how proteins interconnect better to identify possible reasons why certain drug compounds might be causing side effects and also to predict which targets might potentially be valuable for treating disease.”

To appreciate just how pervasive the 800 or so human GPCRs are, you only need to take a deep breath and look at yourself: nestled inside the eye, these proteins detect light and help us see, those in the nose detect scents, while the ones in taste buds let us taste chocolate, sweets and bitter foods.

But these proteins also detect glucose and hormones in the blood, neurotransmitters, or chemicals that help our brain cells communicate, as well as hold cells together, ensuring that tissues don’t fall apart. It’s no surprise then, that when GPCRs go awry, this can lead to brain disorders, diabetes, cancer and a host of other diseases.

In the past, scientists would either focus on the GPCR parts that are easily accessible, such as those sticking out on either side of the cell.

Or, to study the GPCRs in entirety, they would remove the surrounding membrane, which changes the proteins’ properties. Either way, researchers weren’t getting the full picture of how these proteins work. Stagljar's technology has revolutionized the study of membrane proteins, attracting interest from the pharmaceutical industry.

Read here about Stagljar’s work on proteins playing a role in cancer

“Our previous limited knowledge of the GPCRs had already helped us to tremendously improve human health,” Stagljar says. “Think of what we might be able to do if we mapped all these proteins and their interactions and then understand the biological importance of those – this would be a huge step forward for biomedicine.”

Where hard work meets passion, meet brain disorder researcher Yuqing Wang

sgupta — Fri, 13 Feb 2015 16:00:48 +0000

Where hard work meets passion, meet brain disorder researcher Yuqing Wang sgupta Fri, 02/13/2015 - 11:00

Jim Oldfield

Author legacy

Jim Oldfield

Topic

Hospital for Sick Children

Subheadline

PhD student conducts leading-edge research at Sick Kids, volunteers at distress centre – and became a Canadian citizen last year

“Don’t stay in school.” Most kids never hear those words from their parents. But when Yuqing Wang announced she would do a PhD at the University of Toronto, her mother was upset.

Wang’s parents felt she had been in school long enough. They wanted her to get a job and earn money. And they were worried she was neglecting her personal life. As emigrants from China, they had seen too many women struggle to find husbands after years of university.

“It’s a phenomenon in China,” says Wang, now a fifth-year doctoral student in the department of biochemistry. “Many women with higher education have trouble finding partners. They spend a lot of time studying and not much dating. And some men don’t like the idea of women as breadwinners.”

But, after many talks about job and family prospects for doctoral grads in Canada, Wang’s parents warmed up to her plan for more school.

“Now they tell their friends in China, ‘My daughter is doing a PhD at the University of Toronto.’ I think they’re kind of proud,” says Wang.

It helps that in the last five years, Wang has won three scholarships, lead-authored two papers in a respected journal and found a new way to measure an important process in cell death called mitophagy.

Wang is a student in two labs – a choice she was warned against by colleagues rather than family. Some students said that two supervisors could mean double a normal workload. But the researchers with whom Wang studies work closely together on Parkinson’s disease and other brain disorders, and Wang says it’s been a great experience.

She studies mitochondria, which are tiny structures that provide cells with energy. Normally mitochondria break down nutrients and provide fuel for molecules in a process called cellular respiration. But when this process goes awry, mitochondria can release reactive oxygen species, which can kill cells.

A leading theory in Parkinson’s research is that people with the disease have restricted autophagy, or ability to remove damaged mitochondria. These dysfunctional mitochondria then release reactive oxygen species that kill brain cells.

Researchers have found two proteins that prevent the removal of damaged mitochondria in Parkinson’s disease. They hope to create drugs that target those proteins, so they’re altering the function of the proteins and observing the effects on mitochondria. Wang developed a method to measure the rate of mitochondria removal with a microscope, which will help researchers build the knowledge they need for drugs that fight Parkinson’s.

“I really enjoy the discovery part of lab work. The possibility of observing something nobody has seen before is very exciting,” says Wang.

Wang developed an interest in mitochondria as an undergraduate student at ��˾��ֱ��. She did a summer project on yeast mitochondria in the lab of Angus McQuibban, a professor in the department of biochemistry, who is now one of her supervisors. She liked the science and the way McQuibban ran the lab – hands-off, so students control their own projects.

She also liked McQuibban’s’s ethics: passion and hard work.

Wang credits McQuibban and her other PhD supervisor, Peter Kim, for showing her the value of those ethics in the lab. Kim is an assistant professor of biochemistry at ��˾��ֱ�� and a scientist at The Hospital for Sick Children, where Wang spends most of her time.

Kim’s lab studies the creation and degradation of organelles – organ-like structures inside cells – in peroxisome biogenesis disorder, a rare and fatal disease in children. They also study brain disorders and cancer, and recently they found their results may be relevant in Parkinson’s.

Passion and hard work are paying off for Wang outside the lab too. She became a Canadian citizen last August, and while writing her citizenship test she realized she had done little to help her new community. A few days later she saw an ad for the Toronto Distress Centre on the subway and called to volunteer.

“After three months of training I was ready. Some callers just want to chat, others are in acute distress with serious mental health challenges. It’s very rewarding to connect with these people and to help them, even in a small way.” Wang spends about four hours a week at the centre and says she will do similar work wherever she goes.

Wang will likely choose a postdoctoral fellowship in industry as her next career step. She says there is a risk her skills will become so specialized that jobs options begin to narrow.

“But industry postdocs are a great way to continue doing discovery work in the lab, and to get a new perspective on careers in science,” she says.

No doubt someone will counsel against that move. Do her parents know about it? “Not yet,” Wang says. “That’s the next battle.”

Jim Oldfield is a writer with the Faculty of Medicine at the University of Toronto.

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Acting out dreams while asleep could be warning sign of brain disorder

sgupta — Tue, 22 Apr 2014 10:15:42 +0000

Acting out dreams while asleep could be warning sign of brain disorder sgupta Tue, 04/22/2014 - 06:15

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In her most famous scene, Shakespeare's Lady Macbeth (pictured here at the Edinburgh Fringe Festival) is fast asleep yet attempts to wash blood from her hands (photo by Hamish Irvine via Flickr)

Michael Kennedy

Author legacy

Michael Kennedy

Topic

Breaking Research

Parkinson's

Researchers propose biologically based classification system for Parkinson’s disease

��˾��ֱ�� researchers' approach to producing neural cells could yield new treatments for Parkinson’s

Researchers identify a potential new therapeutic target in Parkinson’s disease

��˾��ֱ�� startups win prizes for products helping disabled, injured

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��˾��ֱ�� researcher launches startup to help find new smart drugs

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Read about his latest research findings for Parkinson's

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��˾��ֱ�� study provides new hope for Parkinson’s as elusive proteins come to light

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Where hard work meets passion, meet brain disorder researcher Yuqing Wang

Acting out dreams while asleep could be warning sign of brain disorder