Autism

Creating 'Julia,' the first Muppet on the autism spectrum

Christopher.Sorensen — Fri, 03 Feb 2023 17:07:30 +0000

Creating 'Julia,' the first Muppet on the autism spectrum

Christopher.Sorensen Fri, 02/03/2023 - 12:07

Cutline

Professor Rhonda McEwen recently discussed working with Sesame Street Workshop to create the first Muppet on the autism spectrum. "Julia" made her debut on the Sesame Street TV series in 2017 (photo by Minh Truong)

Daniel Blackwell

Topic

Our Community

Diversity and Inclusion

Autism

U of T Mississauga

Victoria College

Victoria University

When most people think of Sesame Street they envision cherished childhood memories of singalongs and fun with Big Bird and Cookie Monster.

But for Rhonda McEwen, president and vice-chancellor of Victoria University in the ��Ƶ, the show’s loveable cast of Muppets represent something even greater – a form of technology and media that can improve accessibility and inclusivity across the world.

McEwen recently discussed her experience working with Sesame Street Workshop on the first Muppet on the autism spectrum, a red-haired little girl named Julia. As part of Sesame Street in Communities, Julia was created to support families and care providers while creating public awareness about autism. The project made headlines around the world for its ground-breaking inclusion of autism within programming designed for children.

“They reached out to me and said they were gathering a group of the world's leading researchers to inform the project,” said McEwen, who is also a professor at U of T Mississauga’s Institute of Communication, Culture, Information and Technology, during a recent talk held by the Victoria Women’s Association. “Initially, though, they were not going to create a Muppet because they were very costly, take many years and require very careful research.”

As a Canada Research Chair in tactile interfaces, communication and cognition and co-author of the peer-reviewed book Understanding Tablets from Early Childhood to Adulthood, McEwen says it was her research on touchscreen technology for children on the autism spectrum that initially caught the eye of program co-ordinators at the Sesame Street Workshop. 

Serving on an international advisory board for the Sesame Street Workshop, McEwen joined a team of experts tasked with determining how Sesame Street could best provide educational resources to represent autism. The result was a multimedia initiative called Sesame Street and Autism: See Amazing in All Children, which featured Julia in videos, apps and print and digital stories, such as the e-book We’re Amazing 1, 2 3!, which McEwen helped create.

In 2017, Julia appeared in her first Sesame Street episode, titled “Meet Julia.” In the episode, Julia is introduced to audiences as a little girl on the autism spectrum – a creative, friendly child who does things a little differently, or, in the words of fellow Muppet Abby, “in a Julia sort of way.” The 10-minute YouTube video of this episode has since garnered more than 7.7 million views.

McEwen emphasized that Julia was not intended to be a universal depiction of all children on the autism spectrum – a condition that can present itself differently on a case-by-case basis – but was developed through meticulous research and consultation with families. “Every single line of dialogue was carefully scripted and there is meaning behind every expression we chose,” she says.

Even though working on a Muppet may appear to be outside the wheelhouse of somebody with a PhD in information, a master's degree in telecommunications and an MBA in information technology management, McEwen says Julia is like any other form of technology.

“How do we define technology? If technology is how we use science and mathematical thinking to carry out a particular goal or aim, then Julia is a technology,” she says. “Whether we use Julia in her analogue or digital form, we’re using her to spread and share information about autism across the world.”

All technology, says McEwen, can enhance inclusion – an issue of significant importance to her both as a researcher and leader at Victoria University.

“One of the Sesame Street lines I often repeat when speaking with students, staff and faculty is, ‘Who are the people in your neighbourhood?' Getting to know and understand the diverse members of [our] community will allow us to address individual needs so that everyone feels that they belong,” she says.

“Working on Julia has just been one of the best parts of my research career – to see the work that I do translate into real people's lives in a way that some of my most exciting papers do not,” says McEwen.

McEwen, who remains on the advisory board with Sesame Street Workshop, sees plenty of exciting opportunities to continue making a difference in the years ahead.

"Nothing energizes me more than seeing young people inspired by learning, and I have the pleasure of that experience every day at Vic and in my work with Sesame Street."

Activity levels among children with autism spectrum disorder linked to parental behaviour: U of T study

Christopher.Sorensen — Thu, 29 Oct 2020 19:45:44 +0000

Activity levels among children with autism spectrum disorder linked to parental behaviour: U of T study

Christopher.Sorensen Thu, 10/29/2020 - 15:45

Cutline

Researchers at U of T's Faculty of Kinesiology & Physical Education found that roughly three quarters of parents struggle to provide physical activity support for children with autism spectrum disorder (photo by JaySi/iStockImages via Getty Images)

Jelena Damjanovic

Topic

Breaking Research

Autism

Faculty of Kinesiology & Physical Education

Research & Innovation

Children and youth with autism spectrum disorder (ASD) engage in less physical activity than their peers, a ��Ƶ study has found.

The research, published recently in Autism, examined the relationship between parents’ support for physical activity and physical activity levels of children and youth with autism spectrum disorder.

“We know that parent support for physical activity is critical for engaging children and youth with disabilities in physical activity, although it may be especially important for children and youth with ASD due to the barriers they face beyond those experienced by their peers without disabilities,” says Denver Brown, a former post-doctoral researcher at the Faculty of Kinesiology & Physical Education and lead author of the study.

He explains that, at the individual level, children and youth with ASD may engage in less physical activity due to social, behavioural or motor impairments. But there are also environmental factors, he says, such as the limited availability of inclusive physical activity programming and staff who are trained to work with children and youth with ASD in those settings.

“Understanding factors that promote physical activity among children and youth with ASD is critical for shaping lifelong physical activity patterns that are known to be established during these formative life stages,” Brown says.

The study, done in collaboration with researchers from the University of British Columbia, Queens University and York University, focused on a specific sub-sample of participants from a larger five-year National Physical Activity Measurement (NPAM) study that is led by KPE’s Associate Professor Kelly Arbour-Nicitopoulos and funded by Canadian Tire Jumpstart Charities. NPAM looks into the movement behaviours such as physical activity, sedentary behaviour and sleep among Canadian school-aged children and youth with disabilities.

More than 200 parents of children and youth with ASD completed a questionnaire assessing, among other things, behaviours and intentions to support their child’s physical activity, including how often they looked for information or opportunities to become active with their child or how often they made a plan to ensure their child engaged in physical activity.

The study found that, while many parents of children and youth with ASD have strong intentions to provide support for their child’s physical activity, roughly 75 per cent struggle to translate these intentions into action. On average, they are able to provide physical activity support for their children only once per week.

“One potential explanation for this is that parents of children and youth with ASD face barriers that are often out of their control,” says Arbour-Nicitopoulos. “For example, the need to manage their child’s condition may limit additional time for parents to support their child’s regular physical activity participation and to seek out further knowledge of specialized physical activity programming. Some may ultimately view providing physical activity support as a lower priority compared to the many competing demands they face in caring for their child.”

An additional challenge is the fact that the responsibility of supporting children and youth with ASD still largely falls on parents. But the study authors say clinicians have a unique opportunity to address this issue. As primary care providers, they could discuss the importance of physical activity with parents during clinical visits and refer families to a kinesiologist, who could work with parents to improve their use of behavioural regulation strategies – such as planning and goal setting – to provide physical activity support, the authors suggest. Such interventions could be delivered over the phone or via webinars and apps as a potentially cost-effective strategy to provide a structured framework to change parent physical activity support behaviour.

“Our study has shown that, while parents of children and youth with ASD have the best intentions to support their physical activity, this is often not enough,” Arbour-Nicitopoulos says. “By helping parents as well as their children develop the necessary skills to support their child’s physical activity, we would be helping families get a sense of control to act upon their intentions.”

Gene fragment could explain link between autism and cognitive difficulties: U of T study

Christopher.Sorensen — Wed, 29 Jan 2020 21:37:12 +0000

Gene fragment could explain link between autism and cognitive difficulties: U of T study

Christopher.Sorensen Wed, 01/29/2020 - 16:37

Cutline

Thomas Gonatopoulos-Pournatzis, the study's lead author, says the team's research sheds light on the mechanisms that cause autism and may lead to the development of better therapeutic strategies (photo by Jovana Drinjakovic)

Jovana Drinjakovic

Topic

Breaking Research

Donnelly Centre for Cellular & Biomolecular Research

Cell and Systems Biology

Lunenfeld-Tanenbaum Research Institute

Autism

Biochemistry

Faculty of Arts & Science

Faculty of Medicine

Hospital for Sick Children

Molecular Genetics

Mount Sinai Hospital

Physiology

Research & Innovation

Autism is associated with brilliance as well as cognitive difficulty, but how either scenario plays out in the brain is not clear. Now a study by ��Ƶ researchers has found that a tiny gene fragment impacts the brain in a way that could explain swathes of autism cases that come with cognitive challenges.

Researchers led by Benjamin Blencowe, a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research and Faculty of Medicine, and Sabine Cordes, a senior investigator at Sinai Health System’s Lunenfeld-Tanenbaum Research Institute (LTRI), have identified a short gene segment that is crucial for brain development and information processing. Writing in the journal Molecular Cell, the researchers describe how an absence of this segment is sufficient to induce altered social behaviour –a hallmark of autism – in mice, as well as learning and memory deficits, which are seen in a subset of autism cases.

Best known for causing difficulties in social interaction and communication, autism is thought to arise from mishaps in brain wiring during development. It can strike in various ways. Those who experience it can have superior mental ability or need full-time care. Where on the autism spectrum a person falls depends in large part on their genetics, but most cases are idiopathic, or of unknown genetic origin.

“It’s very important to understand the mechanisms that underlie autism, especially in idiopathic forms where it is not clear what the underlying causes are,” says Thomas Gonatopoulos-Pournatzis, a research associate in Blencowe’s lab and lead author of the study. “Not only have we identified a new mechanism that contributes to this disorder, but our work may also offer a more rational development of therapeutic strategies.”

Blencowe’s team had previously uncovered a link between autism and short gene segments, known as microexons, that are predominantly expressed in the brain. Through a process known as alternative splicing, microexons are either spliced in or left out from the final gene transcript before it is translated into a protein. Although small, microexons can have dramatic effects by impacting a protein’s ability to bind its partners as required during brain development. However, how individual microexons contribute to autism is not clear.

The team focused on a specific microexon located in a gene known as eIF4G, which is critical for protein synthesis in the cell. They found that this microexon is overwhelmingly excluded from eIF4G gene transcripts in the brains of autistic individuals.

Hippocampal neurons from a normal mouse (above) and a mouse bred to lack the eIF4G microexon (below). The latter contains fewer particles that represent paused protein synthesis machineries. In these mice, higher levels of protein synthesis in neurons lead to disrupted brain waves and autistic-like behaviors as well as cognitive deficits down the line.

To test if the eIF4G microexon is important for brain function, Gonatopoulos-Pournatzis, together with Cordes’s team, bred mice that lack it. These mice showed social behaviour deficits, such as avoiding social interaction with other mice, establishing a link between the eIFG4 microexon and autistic-like behaviours.

A surprise came when the researchers found that these mice also performed poorly in a learning and memory test, which measures the animals’ ability to associate an environment with a stimulus.

“We could not have imagined that a single microexon would have such an important impact not only on social behaviour but also on learning and memory,” says Gonatopoulos-Pournatzis.

Further analysis revealed that the microexon encodes a part of eIF4G that allows it to associate with the Fragile X mental retardation protein, or FMRP, which is missing from people affected with Fragile X syndrome, a type of intellectual disability. About a third of individuals with Fragile X have features of autism but the link between the two remained unclear – until now.

FMRP and eIF4G work together to act as a brake to hold off protein synthesis until new experience comes along, as the brake is removed by neural activity, the researchers also found.

“It’s important to control brain responses to experience,” says Gonatopoulos-Pournatzis. “This brake in protein synthesis is removed upon experience and we think it allows formation of new memories.”

Without the microexon, however, this brake is weakened and what follows is increased protein production. The newly made proteins, identified in experiments performed with Anne-Claude Gingras, a senior investigator at LTRI and a professor in the department of molecular genetics, form ion channels, receptors and other signaling molecules needed to build synapses and for them to function properly.

However, making too many of these proteins is not a good thing because it leads to the disruption of the type of brain waves involved in synaptic plasticity and memory formation. This is revealed by electrode recordings of mouse brain slices in experiments performed by the teams of Graham Collingridge, a senior investigator at LTRI and a professor in the department of physiology, and Melanie Woodin, a professor of cell and systems biology at U of T and the dean of the Faculty of Arts & Science.

Moreover, an excess of similar kinds of proteins occurs in the absence of FMRP, suggesting a common molecular mechanism for Fragile X and idiopathic autism.

Researchers believe that their findings could help explain a substantial proportion of autism cases for which no other genetic clues are known. The findings also open the door to the development of new therapeutic approaches. One possibility is to increase the splicing of the eIF4G microexon in affected individuals using small molecules as a way to improve their social and cognitive deficits, Blencowe said.

The study would not have been possible without a close collaboration among multiple teams contributing diverse expertise. Blencowe and Gonatopoulos-Pournatzis also worked closely with Julie Forman-Kay, a professor of biochemistry and program head and senior scientist in the molecular medicine program at the Hospital for Sick Children, and Nahum Sonenberg, a professor of biochemistry at McGill University.

The research was made possible by grants from the Canadian Institutes of Health Research, Simon’s Foundation and the Canada First Research Excellence Fund Medicine by Design program, among others.

U of T researchers discover genetic network linked to autism

lanthierj — Mon, 05 Nov 2018 17:12:09 +0000

U of T researchers discover genetic network linked to autism

lanthierj Mon, 11/05/2018 - 12:12

Cutline

Donnelly Centre researchers Thomas Gonatopoulos-Pournatzis (left) and Professor Benjamin Blencowe used the powerful gene editing tool CRISPR to help identify the genes (photo courtesy of the Donnelly Centre)

Topic

Research & Innovation

Researchers at the ��Ƶ have uncovered a network of more than 200 genes linked to autism – a discovery that could lead to new therapies for the common neurological disorder.

The findings are part of a collaborative research program focusing on autism led by Benjamin Blencowe, a professor in U of T’s Donnelly Centre for Cellular & Biomolecular Research and the department of molecular genetics.

“Our study has revealed a mechanism underlying the splicing of very short coding segments found in genes with genetic links to autism,” said Blencowe, who also holds the Banbury Chair of Medical Research at U of T.

“This new knowledge is providing insight into possible ways of targeting this mechanism for therapeutic applications.”

The network of genes uncovered by postdoctoral researcher Thomas Gonatopoulos-Pournatzis, lead author of the study published in the journal Molecular Cell, is involved in controlling alternative splicing. That’s a process that diversifies protein molecules – cells’ building blocks – in the brain and other parts of the body.

Blencowe’s laboratory previously showed that disruption of this process is closely linked to altered brain wiring and behaviour found in autism.

Best known for its effects on social behaviour, autism is thought to be caused by mishaps in brain wiring laid down during embryo development. Hundreds of genes have been linked to autism, making its genetic basis difficult to untangle. Alternative splicing of small gene fragments, or microexons, has emerged as a rare, unifying concept in the molecular basis of autism after Blencowe’s team previously discovered that microexons are disrupted in a large proportion of autistic patients.

Learn how microexons contribute to autism

As tiny protein-coding gene segments, microexons affect the ability of proteins to interact with each other during the formation of neural circuits. Microexons are especially critical in the brain, where they are included into the RNA template for protein synthesis during the splicing process. Splicing enables the utilization of different combinations of protein-coding segments, or exons, as a way of boosting the functional repertoires of protein variants in cells.

And while scientists have a good grasp of how exons, which are about 150 DNA letters long, are spliced, it remained unclear how the much-smaller microexons – a mere 3-27 DNA letters long – are used in nerve cells.

“The small size of microexons’ presents a challenge for the splicing machinery and it has been a puzzle for many years how these tiny exons are recognized and spliced,” Blencowe said.

To answer this question, Gonatopoulos-Pournatzis developed a method for identifying genes that are involved in microexon splicing. Using the powerful gene editing tool CRISPR, and working with Mingkun Wu and Ulrich Braunschweig in the Blencowe lab as well as with the Jason Moffat lab in the Donnelly Centre, Gonatopoulos-Pournatzis removed from cultured brain cells each of the 20,000 genes in the genome to find out which ones are required for microexon splicing.

He identified 233 genes whose diverse roles suggest that microexons are regulated by a wide network of cellular components.

“A really important advantage of this screen is that we’ve been able to capture genes that affect microexon splicing both directly and indirectly and learn how various molecular pathways impinge on this process,” Blencowe said.

Gonatopoulos-Pournatzis was also able to find other factors that work closely with a protein called nSR100/SRRM4m a master regulator of microexon splicing, discovered earlier by the Blencowe lab. Working with Anne-Claude Gingras’s team at Sinai Health System’s Lunenfeld-Tanenbaum Research Institute, they identified proteins called Srsf11 and Rnps1 as forming a molecular complex with nSR100.

Knowing the precise molecular mechanisms of microexon splicing will help guide efforts to develop potential therapeutics for autism and other disorders.

For example, because the splicing of microexons is disrupted in autism, researchers could look for drugs capable of restoring their levels to those seen in unaffected individuals.

“We now better understand the mechanism of how the microexons are recognized and spliced specifically in the brain,” said Gonatopoulos-Pournatzis, who recently won the Donnelly Centre’s newly established Research Excellence Award.

“When you know the mechanism, you can potentially target it using rational approaches to develop therapies for neurodevelopmental disorders.”

The study was supported by research grants from the Canadian Institutes for Health Research, Medicine by Design as part of the Canada First Research Excellence Fund and the Simmons Foundation.

Autism: U of T expert on the large gender divide

rasbachn — Mon, 21 Aug 2017 17:58:31 +0000

Autism: U of T expert on the large gender divide

rasbachn Mon, 08/21/2017 - 13:58

Cutline

Girls with autism may have trouble maintaining friendships, says U of T's Dr. Meng-Chuan Lai (photo by Jaymis Loveday via Flickr)

Author legacy

Dr. Meng-Chuan Lai

Topic

Subheadline

Girls often aren't diagnosed because of stereotypes about gender – and autism

More boys than girls are on the autism spectrum, and there can be large differences in symptoms between genders. Stereotypes about gender and autism – often lead to girls with the condition flying under the radar, says Dr. Meng-Chuan Lai, an assistant professor in U of T’s department of psychiatry and a psychiatrist at the Centre for Addiction and Mental Health and the Hospital for Sick Children.

Our long-standing beliefs about the signs of autism are derived mostly from boys, he explains in the current edition of Doctors' Notes, a weekly column in the Toronto Star written by members of U of T's Faculty of Medicine. Autism is marked by intense and narrow interests, but when girls are single-minded in their focus on people, books, fashion or comics, it often gets overlooked. As well, girls with autism may have a rich fantasy world that can go unnoticed.

Lai writes that girls on the spectrum may seem shy, quiet or anxious, but adults don’t recognize the signs because they associate these traits more with girls than boys. Autism is characterized by difficulty making eye contact and communicating with other people, but because girls are often under social pressure to please and fit in, they are more likely to find coping mechanisms when dealing with people. That can lead to sensory or social overload, so autistic girls often need time to be alone and de-stress after coming home from school.

Some good news: Awareness about the differing signs of autism has grown in the past decade.

Read the entire Doctors’ Notes column in the Toronto Star

Big data helps autism research: U of T team identifies 18 new genes increasing risk

ullahnor — Thu, 13 Apr 2017 20:00:18 +0000

Big data helps autism research: U of T team identifies 18 new genes increasing risk

ullahnor Thu, 04/13/2017 - 16:00

Cutline

U of T researchers Stephen Scherer (left) and Ryan Huen (right) are part of the MSSNG autism genomics project (photo by Robert Teteruck/SickKids)

Jim Oldfield

Author legacy

Jim Oldfield

Topic

Artificial Intelligence

Scientists in the world’s largest autism genomics project recently identified 18 new genes that increase risk for the condition.

Some of the genes seen in participants also carry risk for heart disease, diabetes and other conditions, opening the potential for more personalized genetic counselling.

The results of the project, named MSSNG, provide more evidence that each person’s autism is unique, meaning researchers will still need a lot more genomic data before they can sort and target the many forms of the condition. However, some families are already benefitting. The MSSNG project includes whole-genome data from more than 7,000 individuals affected by autism, and that data is stored on Google Cloud, which allows access to researchers around the world.

Professor Stephen Scherer, director of both the McLaughlin Centre at the ��Ƶ and the Centre for Applied Genomics at the Hospital for Sick Children, is the senior investigator for MSSNG.

He spoke with U of T's Jim Oldfield about how the cloud is enabling a new kind of open science on autism, and what needs to happen next for big data to deliver on its potential to treat the most baffling medical conditions.

How did the MSSNG project come about?

Genome sequencing generates massive amounts of data, and the need to deal with those terabytes of information is what put us into the cloud environment.

The project came together four years ago when we decided to make all that data available. The original vision a few of us had was for truly open science, where you could type a keyword into a database, say if you’re looking for which individuals carry a gene.

We found out along the way that we need more open consent, in part because we’re dealing with clinical research data, even though it’s anonymized. So we now have a system where you apply through a data access committee. You can get anything you want in the cloud, including raw reads from the sequencers and new analytics tools we've developed. Almost 100 researchers at dozens of institutions are using the system, and we expect those numbers to grow. It’s probably one of the most open-science genetics projects right now.

Why is this technology well-suited for autism research?

We need to take this approach because autism is extremely heterogeneous in terms of how it presents clinically and the underlying genetics. There are well over 100 different forms, which is why we sometimes call them the autisms.

To subcategorize these conditions, we need big numbers and whole genomes. We calculated that to get all low hanging fruit – the highly penetrative autisms with the most common genetic variants – we’d need about 10,000 families. To find new impactful variants, including copy number variations or small insertions and deletions, some of which are in the noncoding regions of the genome, we’ll likely need up to 100,000.

Will machine learning help analyze that data?

I hope so. [U of T Professor] Brendan Frey and his group published a paper in Science a couple of years ago using MSSNG data in its early form. They used deep genomics algorithms to analyze hundreds of thousands of variants. We published a follow-up paper using his programs to look for splicing differences in autism subjects versus controls. These are some of the first papers that convincingly show non-genic regions of the genome can be involved in autism. So the short answer is we’re already using machine learning to mine the data we have, and other groups are doing it as well. We do think U of T will have a competitive advantage here.

How is MSSNG benefiting patients now?

We’ve found a total of 63 genes and mutations that increase risk for autism through this project.

That data is communicated back to families that are part of the study, through a genetic counsellor in cases where it’s relevant. Sometimes other conditions are implicated such as epilepsy, anxiety or sleep/mood disorders. In others, a formal diagnosis can help encourage earlier behavioral interventions.

A genetic profile that matches a known subtype of autism can also affect prognosis and assessment of familial recurrence risk. And we’re linking families with one another in cases where they may benefit by talking about what worked and what didn’t. In the future, this data should facilitate clinical trials based on a small number of key neurological pathways affected by the many genetic variants in autism.

What progress might we see in the next five years?

I often say autism is about 10 years behind cancer in terms of how we use genomic data. But, we’re only behind because we started later.

Some people don’t think autism should be an area of research, and some families don’t want interventions. But most want investment and research so the demand for data is very high.

If had my dream – and I think this will happen in Ontario within three years – every child with a diagnosis would have his or her genome sequenced. For about 20 per cent of families, we can now explain why autism comes about in their child. Previous technologies only looked at two per cent of the genome, the genes. Now, most leading-edge labs are studying the other 98 per cent, and whole-genome sequencing provides the fundamental road map for those experiments. We are linking all that high-quality data together and using it to decode evolution. It’s a very exciting time.

Nature Neuroscience published the recent results from MSSNG, which is a collaboration between SickKids, Autism Speaks, Verily (formerly Google Life Sciences) and researchers at the ��Ƶ.