Autism / en Creating 'Julia,' the first Muppet on the autism spectrum /news/creating-julia-first-muppet-autism-spectrum <span class="field field--name-title field--type-string field--label-hidden">Creating 'Julia,' the first Muppet on the autism spectrum</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/TRU_3782-crop.jpg?h=afdc3185&amp;itok=ssj9exye 370w, /sites/default/files/styles/news_banner_740/public/TRU_3782-crop.jpg?h=afdc3185&amp;itok=BjbMPlmW 740w, /sites/default/files/styles/news_banner_1110/public/TRU_3782-crop.jpg?h=afdc3185&amp;itok=XedH_W5g 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/TRU_3782-crop.jpg?h=afdc3185&amp;itok=ssj9exye" alt="&quot;&quot;"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-02-03T12:07:30-05:00" title="Friday, February 3, 2023 - 12:07" class="datetime">Fri, 02/03/2023 - 12:07</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Professor Rhonda McEwen&nbsp;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)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/taxonomy/term/6890" hreflang="en">Daniel Blackwell</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/diversity-and-inclusion" hreflang="en">Diversity and Inclusion</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/u-t-mississauga" hreflang="en">U of T Mississauga</a></div> <div class="field__item"><a href="/news/tags/victoria-college" hreflang="en">Victoria College</a></div> <div class="field__item"><a href="/news/tags/victoria-university" hreflang="en">Victoria University</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>When most people think of&nbsp;<em>Sesame Street</em>&nbsp;they envision cherished childhood memories of singalongs and fun with Big Bird and Cookie Monster.</p> <p>But for&nbsp;<strong>Rhonda McEwen</strong>, president and vice-chancellor of Victoria University in the șüÀêÊÓÆ”,&nbsp;the show’s&nbsp;loveable cast of Muppets represent something even greater – a form of technology and media that can improve accessibility and inclusivity across the world.&nbsp;</p> <p>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.&nbsp;As part of&nbsp;<a href="https://sesamestreetincommunities.org/" target="_blank">Sesame Street in Communities</a>, Julia was created to support families and care providers while creating public awareness about autism. The project made headlines around the world&nbsp;for its ground-breaking inclusion of autism within programming designed for children.&nbsp;</p> <p>“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&nbsp;Institute of Communication, Culture, Information and Technology,&nbsp;during a recent talk held by the&nbsp;<a href="https://vic.utoronto.ca/alumni/vwa/">Victoria Women’s Association</a>. “Initially, though, they were not going to create a Muppet because they were very costly, take many years and require very careful research.”&nbsp;</p> <p>As a&nbsp;Canada Research Chair in tactile interfaces, communication and cognition&nbsp;and co-author of the peer-reviewed book&nbsp;<a href="https://www.routledge.com/Understanding-Tablets-from-Early-Childhood-to-Adulthood-Encounters-with/McEwen-Dube/p/book/9781138229433" target="_blank"><em>Understanding Tablets from Early Childhood to Adulthood</em></a>, 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. &nbsp;</p> <p>Serving on an international advisory board for the Sesame Street Workshop, McEwen joined a team of experts tasked with determining how&nbsp;<em>Sesame Street</em>&nbsp;could best provide educational resources to represent autism. The result was a multimedia initiative called&nbsp;Sesame Street and Autism: See Amazing in All Children,&nbsp;which featured Julia in videos, apps and print and digital stories, such as the e-book&nbsp;<a href="https://autism.sesamestreet.org/storybook/we-are-amazing/" target="_blank"><em>We’re Amazing 1, 2 3!</em></a>, which McEwen helped create.&nbsp;</p> <div class="media_embed" height="422px" width="750px"><iframe allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share" allowfullscreen frameborder="0" height="422px" src="https://www.youtube.com/embed/dKCdV20zLMs" title="YouTube video player" width="750px"></iframe></div> <p>&nbsp;</p> <p>In 2017, Julia appeared in her first&nbsp;<em>Sesame Street&nbsp;</em>episode, titled “Meet Julia.”&nbsp;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.”&nbsp;The 10-minute YouTube video of this episode has since garnered more than 7.7 million views.&nbsp;</p> <p>McEwen emphasized that Julia was not intended to be a universal depiction of all children on the autism spectrum&nbsp;– 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.&nbsp;&nbsp;</p> <p>Even though working on a Muppet may appear to be outside the wheelhouse of somebody with a PhD in information, a master's degree&nbsp;in telecommunications&nbsp;and an MBA in information technology management, McEwen says Julia is like any other form of technology.&nbsp;</p> <p>“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.”&nbsp;</p> <p>All technology, says McEwen, can enhance inclusion&nbsp;–&nbsp;an issue of significant importance to her both as a researcher and leader at&nbsp;Victoria University.</p> <p>“One of the&nbsp;<em>Sesame Street&nbsp;</em>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.&nbsp;</p> <p>“Working on Julia has just been one of the best parts of my research career&nbsp;– 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.&nbsp;&nbsp;</p> <p>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.</p> <p>"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&nbsp;<em>Sesame Street</em>."</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Fri, 03 Feb 2023 17:07:30 +0000 Christopher.Sorensen 179629 at Activity levels among children with autism spectrum disorder linked to parental behaviour: U of T study /news/activity-levels-among-children-autism-spectrum-disorder-linked-parental-behaviour-u-t-study <span class="field field--name-title field--type-string field--label-hidden">Activity levels among children with autism spectrum disorder linked to parental behaviour: U of T study</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/GettyImages-827858252.jpg?h=afdc3185&amp;itok=sidfDV4E 370w, /sites/default/files/styles/news_banner_740/public/GettyImages-827858252.jpg?h=afdc3185&amp;itok=mYLPO8Tq 740w, /sites/default/files/styles/news_banner_1110/public/GettyImages-827858252.jpg?h=afdc3185&amp;itok=gKX0ufj4 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/GettyImages-827858252.jpg?h=afdc3185&amp;itok=sidfDV4E" alt="Father takes his two children cycling through a forest trail"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2020-10-29T15:45:44-04:00" title="Thursday, October 29, 2020 - 15:45" class="datetime">Thu, 10/29/2020 - 15:45</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Researchers at U of T's Faculty of Kinesiology &amp; 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)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jelena-damjanovic" hreflang="en">Jelena Damjanovic</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/faculty-kinesiology-physical-education" hreflang="en">Faculty of Kinesiology &amp; Physical Education</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Children and youth with autism spectrum disorder (ASD) engage in less physical activity than their peers, a&nbsp;șüÀêÊÓÆ” study has found.</p> <p>The research, <a href="https://journals.sagepub.com/doi/10.1177/1362361320922658">published recently in&nbsp;<em>Autism</em></a>, examined the relationship between parents’ support for physical activity and physical activity levels of children and youth with autism spectrum disorder.&nbsp;<br> <br> “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&nbsp;<strong>Denver Brown</strong>, a former post-doctoral researcher at the Faculty of Kinesiology &amp; Physical Education&nbsp;and lead author of the study.<br> <br> 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&nbsp;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.&nbsp;<br> <br> “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.<br> <br> The study,&nbsp;done in collaboration with researchers from the University of British Columbia, Queens University and York University,&nbsp;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&nbsp;<strong>Kelly Arbour-Nicitopoulos</strong>&nbsp;and funded by Canadian Tire Jumpstart Charities. NPAM looks into the movement behaviours&nbsp;such as physical activity, sedentary behaviour and sleep&nbsp;among Canadian school-aged children and youth with disabilities.&nbsp;<br> <br> 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&nbsp;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.&nbsp;<br> <br> 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&nbsp;struggle to translate these intentions into action. On average, they are able to provide physical activity support for their children only once per week.<br> <br> “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.”<br> <br> 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&nbsp;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.&nbsp;<br> <br> “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,”&nbsp;Arbour-Nicitopoulos says.&nbsp;“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.”</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Thu, 29 Oct 2020 19:45:44 +0000 Christopher.Sorensen 166199 at Gene fragment could explain link between autism and cognitive difficulties: U of T study /news/gene-fragment-could-explain-link-between-autism-and-cognitive-difficulties-u-t-study <span class="field field--name-title field--type-string field--label-hidden">Gene fragment could explain link between autism and cognitive difficulties: U of T study</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/Thomas%20alone.jpg?h=afdc3185&amp;itok=c0D4ctza 370w, /sites/default/files/styles/news_banner_740/public/Thomas%20alone.jpg?h=afdc3185&amp;itok=NmdNfNdR 740w, /sites/default/files/styles/news_banner_1110/public/Thomas%20alone.jpg?h=afdc3185&amp;itok=YAOGPurg 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/Thomas%20alone.jpg?h=afdc3185&amp;itok=c0D4ctza" alt="Thomas Gonatopoulos-Pournatzis looks out a window with a hallway in the background"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2020-01-29T16:37:12-05:00" title="Wednesday, January 29, 2020 - 16:37" class="datetime">Wed, 01/29/2020 - 16:37</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">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)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jovana-drinjakovic" hreflang="en">Jovana Drinjakovic</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/donnelly-centre-cellular-biomolecular-research" hreflang="en">Donnelly Centre for Cellular &amp; Biomolecular Research</a></div> <div class="field__item"><a href="/news/tags/cell-and-systems-biology" hreflang="en">Cell and Systems Biology</a></div> <div class="field__item"><a href="/news/tags/lunenfeld-tanenbaum-research-institute" hreflang="en">Lunenfeld-Tanenbaum Research Institute</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/biochemistry" hreflang="en">Biochemistry</a></div> <div class="field__item"><a href="/news/tags/faculty-arts-science" hreflang="en">Faculty of Arts &amp; Science</a></div> <div class="field__item"><a href="/news/tags/faculty-medicine" hreflang="en">Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/hospital-sick-children" hreflang="en">Hospital for Sick Children</a></div> <div class="field__item"><a href="/news/tags/molecular-genetics" hreflang="en">Molecular Genetics</a></div> <div class="field__item"><a href="/news/tags/mount-sinai-hospital" hreflang="en">Mount Sinai Hospital</a></div> <div class="field__item"><a href="/news/tags/physiology" hreflang="en">Physiology</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>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 șüÀêÊÓÆ” 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.</p> <p>Researchers led by&nbsp;<strong>Benjamin Blencowe</strong>, a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research and Faculty of Medicine, and&nbsp;<strong>Sabine Cordes</strong>, 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&nbsp;<em>Molecular Cell</em>, the researchers&nbsp;<a href="https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30006-X" rel="noopener noreferrer" target="_blank">describe how an absence of this segment is sufficient to induce altered social behaviour –a hallmark of autism –&nbsp;in mice, as well as learning and memory deficits</a>, which are seen in a subset of autism cases.</p> <p>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.</p> <p>“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&nbsp;<strong>Thomas Gonatopoulos-Pournatzis</strong>, 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.”</p> <p>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.</p> <p>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.</p> <p><img class="migrated-asset" src="/sites/default/files/neurons%20%282%29.jpg" alt></p> <p><em>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.</em></p> <p>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.</p> <p>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.</p> <p>“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.</p> <p>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.</p> <p>FMRP&nbsp;and&nbsp;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.</p> <p>“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.”</p> <p>Without the microexon, however, this brake is weakened and what follows is increased protein production. The newly made proteins, identified in experiments performed with&nbsp;<strong>Anne-Claude Gingras</strong>, 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.</p> <p>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&nbsp;in experiments performed by the teams of&nbsp;<strong>Graham Collingridge</strong>, a senior investigator at LTRI and a professor in the department of physiology, and&nbsp;<strong>Melanie Woodin</strong>, a professor of cell and systems biology at U of T and the dean of the Faculty of Arts &amp; Science.</p> <p>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.</p> <p>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.</p> <p>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&nbsp;<strong>Julie Forman-Kay</strong>, a professor of biochemistry and program head and senior scientist in the molecular medicine program at the Hospital for Sick Children, and&nbsp;Nahum Sonenberg, a professor of biochemistry at McGill University.</p> <p>The research was made possible by grants from the Canadian Institutes of Health Research, Simon’s Foundation and the&nbsp;Canada First Research Excellence Fund Medicine by Design program, among others.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Wed, 29 Jan 2020 21:37:12 +0000 Christopher.Sorensen 162168 at U of T researchers discover genetic network linked to autism /news/u-t-researchers-discover-genetic-network-linked-autism <span class="field field--name-title field--type-string field--label-hidden">U of T researchers discover genetic network linked to autism </span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2018-11-05-autism-2.jpg?h=afdc3185&amp;itok=1j2bndqV 370w, /sites/default/files/styles/news_banner_740/public/2018-11-05-autism-2.jpg?h=afdc3185&amp;itok=YN1mZL8G 740w, /sites/default/files/styles/news_banner_1110/public/2018-11-05-autism-2.jpg?h=afdc3185&amp;itok=AUKcFtHT 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2018-11-05-autism-2.jpg?h=afdc3185&amp;itok=1j2bndqV" alt="photo of Professor Blencowe and the lead researcher seated at a desk, reviewing study"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>lanthierj</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2018-11-05T12:12:09-05:00" title="Monday, November 5, 2018 - 12:12" class="datetime">Mon, 11/05/2018 - 12:12</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">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)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jovana-drinjakovic" hreflang="en">Jovana Drinjakovic</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/global" hreflang="en">Global</a></div> <div class="field__item"><a href="/news/tags/graduate-students" hreflang="en">Graduate Students</a></div> <div class="field__item"><a href="/news/tags/medicine" hreflang="en">Medicine</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers at the șüÀêÊÓÆ” 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.</p> <p>The findings are part of a collaborative research program focusing on autism led by <a href="http://www.thedonnellycentre.utoronto.ca/content/benjamin-blencowe"><strong>Benjamin Blencowe</strong>, a professor in U of T’s Donnelly Centre for Cellular &amp; Biomolecular Research</a> and the department of molecular genetics.&nbsp;</p> <p>“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.&nbsp;</p> <p>“This new knowledge is providing insight into possible ways of targeting this mechanism for therapeutic applications.”</p> <p>The network of genes uncovered by postdoctoral researcher <strong>Thomas Gonatopoulos-Pournatzis</strong>, lead author of t<a href="https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30840-2">he study published in the journal </a><em><a href="https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30840-2">Molecular Cell</a>,</em>&nbsp;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.&nbsp;</p> <p>Blencowe’s laboratory previously showed that disruption of this process is closely linked to altered brain wiring and behaviour found in autism.</p> <p>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.</p> <h3><a href="http://www.thedonnellycentre.utoronto.ca/news/one-proteins-sweeping-influence-autism-revealed">Learn how microexons contribute to autism</a></h3> <h3><img alt="illustration of the molecular process" class="media-image attr__typeof__foaf:Image img__fid__9543 img__view_mode__media_large attr__format__media_large" src="/sites/default/files/2018-11-05-autism1.jpg" style="width: 750px; height: 410px; margin-top: 20px; margin-bottom: 20px;" typeof="foaf:Image"></h3> <p>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.</p> <p>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&nbsp;–&nbsp;a mere 3-27 DNA letters long – are used in nerve cells.</p> <p>“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.</p> <p>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 <strong>Mingkun Wu</strong> and <strong>Ulrich Braunschweig</strong> in the Blencowe lab as well as with <a href="http://www.thedonnellycentre.utoronto.ca/content/jason-moffat">the&nbsp;<strong>Jason Moffat</strong>&nbsp;lab in the Donnelly Centre</a>, 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.&nbsp;</p> <p>He identified 233 genes whose diverse roles suggest that microexons are regulated by a wide network of cellular components.</p> <p>“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.</p> <p>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 <strong>Anne-Claude Gingras</strong>’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.</p> <p>Knowing the precise molecular mechanisms of microexon splicing will help guide efforts to develop potential therapeutics for autism and other disorders.</p> <p>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.</p> <p>“We now better understand the mechanism of how the microexons are recognized and spliced specifically in the brain,” said&nbsp;Gonatopoulos-Pournatzis, who <a href="http://www.thedonnellycentre.utoronto.ca/news/inaugural-research-excellence-awards-recognize-collaborative-science">recently won the Donnelly Centre’s newly established Research Excellence Award</a>.</p> <p>“When you know the mechanism, you can potentially target it using rational approaches to develop therapies for neurodevelopmental disorders.”</p> <p>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.&nbsp;</p> <p>&nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Mon, 05 Nov 2018 17:12:09 +0000 lanthierj 146444 at Autism: U of T expert on the large gender divide /news/autism-u-t-expert-large-gender-divide <span class="field field--name-title field--type-string field--label-hidden">Autism: U of T expert on the large gender divide </span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/Girl%20playing%20from%20Flickr.jpg?h=2fe880c3&amp;itok=FUcqnUPH 370w, /sites/default/files/styles/news_banner_740/public/Girl%20playing%20from%20Flickr.jpg?h=2fe880c3&amp;itok=Jooa3QEG 740w, /sites/default/files/styles/news_banner_1110/public/Girl%20playing%20from%20Flickr.jpg?h=2fe880c3&amp;itok=cfS_d_O7 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/Girl%20playing%20from%20Flickr.jpg?h=2fe880c3&amp;itok=FUcqnUPH" alt="Girl playing with a ball photo"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>rasbachn</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2017-08-21T13:58:31-04:00" title="Monday, August 21, 2017 - 13:58" class="datetime">Mon, 08/21/2017 - 13:58</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Girls with autism may have trouble maintaining friendships, says U of T's Dr. Meng-Chuan Lai (photo by Jaymis Loveday via Flickr)</div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Dr. Meng-Chuan Lai</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/city-culture" hreflang="en">City &amp; Culture</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/doctors-notes-0" hreflang="en">Doctors' Notes</a></div> <div class="field__item"><a href="/news/tags/faculty-medicine" hreflang="en">Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">Girls often aren't diagnosed because of stereotypes about gender – and autism</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>More boys than girls are on the autism spectrum, and there can be large differences in symptoms between genders. Stereotypes about gender and autism –&nbsp;often lead to girls with the condition flying under the radar, says <strong>Dr.&nbsp;Meng</strong><strong>-Chuan Lai</strong>, 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.</p> <p>Our long-standing beliefs about the signs of autism are derived mostly from boys, he&nbsp;<strong>&nbsp;</strong>explains&nbsp;<a href="https://www.thestar.com/life/health_wellness/2017/08/21/learn-to-recognize-autism-symptoms-in-girls.html">in the current edition of Doctors' Notes</a>, a weekly column in the&nbsp;<em>Toronto Star</em>&nbsp;written&nbsp;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.</p> <p>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.</p> <p>Some good news: Awareness about the differing signs of autism has grown in the past decade.</p> <hr> <p><a href="https://www.thestar.com/life/health_wellness/2017/08/21/learn-to-recognize-autism-symptoms-in-girls.html">Read the entire Doctors’ Notes column in the Toronto Star</a></p> <p>&nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Mon, 21 Aug 2017 17:58:31 +0000 rasbachn 113189 at Big data helps autism research: U of T team identifies 18 new genes increasing risk /news/big-data-helps-autism-research-u-t-team-identifies-18-new-genes-increasing-risk <span class="field field--name-title field--type-string field--label-hidden">Big data helps autism research: U of T team identifies 18 new genes increasing risk</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2017-04-13-stephen-scherer.jpg?h=3ebe9e72&amp;itok=1m8cxy6g 370w, /sites/default/files/styles/news_banner_740/public/2017-04-13-stephen-scherer.jpg?h=3ebe9e72&amp;itok=DM8rSsFW 740w, /sites/default/files/styles/news_banner_1110/public/2017-04-13-stephen-scherer.jpg?h=3ebe9e72&amp;itok=tGOT43xv 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2017-04-13-stephen-scherer.jpg?h=3ebe9e72&amp;itok=1m8cxy6g" alt="photo of stephen scherer and ryan huen"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>ullahnor</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2017-04-13T16:00:18-04:00" title="Thursday, April 13, 2017 - 16:00" class="datetime">Thu, 04/13/2017 - 16:00</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">U of T researchers Stephen Scherer (left) and Ryan Huen (right) are part of the MSSNG autism genomics project (photo by Robert Teteruck/SickKids)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jim-oldfield" hreflang="en">Jim Oldfield</a></div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Jim Oldfield</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/global-lens" hreflang="en">Global Lens</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/genes" hreflang="en">Genes</a></div> <div class="field__item"><a href="/news/tags/big-data" hreflang="en">Big Data</a></div> <div class="field__item"><a href="/news/tags/genomic-data" hreflang="en">Genomic Data</a></div> <div class="field__item"><a href="/news/tags/faculty-medicine" hreflang="en">Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/artificial-intelligence" hreflang="en">Artificial Intelligence</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Scientists in the world’s largest autism genomics project recently identified 18 new genes that increase risk for the condition.</p> <p>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.</p> <p>The results of the project, named MSSNG,&nbsp;provide&nbsp;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.</p> <p>Professor <strong>Stephen Scherer</strong>,&nbsp;director of both the McLaughlin Centre at the șüÀêÊÓÆ” and the Centre for Applied Genomics at the Hospital for Sick Children, is the senior investigator for <a href="https://www.mss.ng/">MSSNG</a>.</p> <p>He spoke with U of T's <strong>Jim Oldfield</strong> 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.</p> <hr> <p><strong>How did the MSSNG project come about?</strong></p> <p>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.</p> <p>The project came together four years ago&nbsp;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.</p> <p>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.</p> <p><strong>Why is this technology well-suited for autism research?</strong></p> <p>We need to take this approach because autism is extremely heterogeneous&nbsp;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.</p> <p>To subcategorize these conditions, we need big numbers and whole genomes. We calculated that to get all low hanging fruit –&nbsp;the highly penetrative autisms with the most common genetic variants&nbsp;–&nbsp;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.</p> <p><strong>Will machine learning help analyze that data?</strong></p> <p>I hope so. <a href="http://science.sciencemag.org/content/347/6218/1254806">[U of T Professor] <strong>Brendan Frey</strong> and his group published a paper in <em>Science</em></a> 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.</p> <p><strong>How is MSSNG benefiting patients now?</strong></p> <p>We’ve found a total of 63 genes and mutations that increase risk for autism&nbsp;through this project.</p> <p>That data is communicated back to families that are part of the study, through a genetic counsellor&nbsp;in cases where it’s relevant. Sometimes other conditions are implicated&nbsp;such as epilepsy, anxiety or sleep/mood disorders. In others, a formal diagnosis can help encourage earlier behavioral interventions.</p> <p>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&nbsp;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.</p> <p><strong>What progress might we see in the next five years?</strong></p> <p>I often say autism is about 10 years behind cancer&nbsp;in terms of how we use genomic data. But, we’re only behind because we started later.</p> <p>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&nbsp;so the demand for data is very high.</p> <p>If had my dream –&nbsp;and I think this will happen in Ontario within three years –&nbsp;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.</p> <p><a href="http://www.nature.com/neuro/journal/v20/n4/full/nn.4524.html"><em>Nature Neuroscience</em> published the recent results from MSSNG</a>, which is a collaboration between SickKids, Autism Speaks, Verily (formerly Google Life Sciences) and researchers at the șüÀêÊÓÆ”.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Thu, 13 Apr 2017 20:00:18 +0000 ullahnor 106715 at Machine learning reveals unexpected genetic roots of cancers, autism and other disorders /news/machine-learning-reveals-unexpected-genetic-roots-cancers-autism-and-other-disorders <span class="field field--name-title field--type-string field--label-hidden">Machine learning reveals unexpected genetic roots of cancers, autism and other disorders</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>sgupta</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2014-12-18T04:41:54-05:00" title="Thursday, December 18, 2014 - 04:41" class="datetime">Thu, 12/18/2014 - 04:41</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"> Brendan Frey (centre) with first co-authors Leo Lee and Hui Xiong (Photo by Jennifer Wilson)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/marit-mitchell" hreflang="en">Marit Mitchell</a></div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Marit Mitchell</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/faculty-arts-science" hreflang="en">Faculty of Arts &amp; Science</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/brendan-frey" hreflang="en">Brendan Frey</a></div> <div class="field__item"><a href="/news/tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/news/tags/engineering" hreflang="en">Engineering</a></div> <div class="field__item"><a href="/news/tags/global" hreflang="en">Global</a></div> <div class="field__item"><a href="/news/tags/health" hreflang="en">Health</a></div> <div class="field__item"><a href="/news/tags/international" hreflang="en">International</a></div> <div class="field__item"><a href="/news/tags/medicine" hreflang="en">Medicine</a></div> <div class="field__item"><a href="/news/tags/research" hreflang="en">Research</a></div> <div class="field__item"><a href="/news/tags/top-stories" hreflang="en">Top Stories</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">Researchers from engineering, biology and medicine teach computers to ‘read the human genome’ and rate likelihood of mutations causing disease, opening vast new possibilities for medicine</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>In the decade since the genome was sequenced in 2003, scientists, engineers and doctors have struggled to answer an all-consuming question: Which DNA mutations cause disease?&nbsp;</p> <p>A new computational technique developed at the șüÀêÊÓÆ” may now be able to tell us.</p> <p>A Canadian research team led by Professor<strong> Brendan Frey</strong> has developed the first method for ‘ranking’ genetic mutations based on how living cells ‘read’ DNA, revealing how likely any given alteration is to cause disease. They used their method to discover unexpected genetic determinants of autism, hereditary cancers and spinal muscular atrophy, a leading genetic cause of infant mortality.</p> <p>Their findings appear in the December 18&nbsp;issue of the leading journal <em><a href="http://www.sciencemag.org/">Science</a>&nbsp;</em>and are already&nbsp;grabbing headlines. (Read the article in <a href="https://www.quantamagazine.org/20141218-machine-intelligence-cracks-genetic-controls/">Quanta Magazine</a>; <a href="http://www.theglobeandmail.com/news/national/canadian-team-makes-breakthrough-in-quest-to-unlock-dnas-secrets/article22147537/">read the Globe and Mail story</a>; <a href="http://www.autismspeaks.org/science/science-news/machine-learning-lets-researchers-search-genome-new-autism-clues">see&nbsp;coverage at autismspeaks.org</a>.)</p> <p>Think of the human genome as a mysterious text, made up of three billion letters.</p> <p>“Over the past decade, a huge amount of effort has been invested into searching for mutations in the genome that cause disease, without a rational approach to understanding why they cause disease,” said&nbsp;Frey. “This is because scientists didn’t have the means to understand the text of the genome and how mutations in it can change the meaning of that text.”</p> <p>It's a puzzle that Frey points out was captured by biologist Eric Lander of the Massachusetts Institute of Technology in a famous quote: “Genome. Bought the book. Hard to read.”&nbsp;</p> <p><img alt src="/sites/default/files/2014-12-18-dominoes-machine-learning.jpg" style="width: 250px; height: 313px; margin: 10px; float: right;">What was Frey’s approach? Scientists&nbsp;know that certain sections of the text, called exons, describe the proteins that are the building blocks of all living cells. What wasn’t appreciated until recently is that other sections, called introns, contain instructions for how to cut and paste exons together, determining which proteins will be produced. This ‘splicing’ process is a crucial step in the cell’s process of converting DNA into proteins, and its disruption is known to contribute to many diseases.&nbsp;</p> <p>(<em>Image at right: artist’s conception of how disease-causing genetic mutations reside with long&nbsp;chains of DNA; photo by Jessica Wilson.</em>)</p> <p>Most research into the genetic roots of disease has focused on mutations within exons, but increasingly scientists are finding that diseases can’t be explained by these mutations. Frey’s team took a completely different approach, examining changes to text that provides instructions for splicing, most of which is in introns.</p> <p>Frey’s team used a new technology called ‘deep learning’ to teach a computer system to scan a piece of DNA, read the genetic instructions that specify how to splice together sections that code for proteins, and determine which proteins will be produced.&nbsp;</p> <p>Unlike other machine learning methods, deep learning can make sense of incredibly complex relationships, such as those found in living systems in biology and medicine.</p> <p>“The success of our project relied crucially on using the latest deep learning methods to analyze the most advanced experimental biology data,” said&nbsp;Frey, whose team included members from U of T’s Faculty of Applied Science &amp; Engineering, Faculty of Medicine and the Terrence Donnelly Centre for Cellular and Biomolecular Research, as well as Microsoft Research and the Cold Spring Harbor Laboratory.</p> <p>“My collaborators and our graduate students and postdoctoral fellows are world-leading experts in these areas.”&nbsp;</p> <p><iframe allowfullscreen frameborder="0" height="315" src="//www.youtube.com/embed/Zp-HcC5wQ1k?rel=0" width="560"></iframe></p> <p>Once they had taught their system how to read the text of the genome, Frey’s team used it to search for mutations that cause splicing to go wrong. They found that their method correctly predicted 94 per cent of the genetic culprits behind well-studied diseases such as spinal muscular atrophy and colorectal cancer, but more importantly, made accurate predictions for mutations that had never been seen before.</p> <p>They then launched a huge effort to tackle a condition with complex genetic underpinnings: autism spectrum disorder.</p> <p>“With autism there are only a few dozen genes definitely known to be involved and these account for a small proportion of individuals with this condition,” said&nbsp;Frey.&nbsp;</p> <p>In collaboration with Dr. <strong>Stephen Scherer</strong>, senior scientist and director of the șüÀêÊÓÆ” McLaughlin Centre and&nbsp;The Centre for Applied Genomics at SickKids, Frey’s team compared mutations discovered in the whole genome sequences of children with autism, but not in controls. Following the traditional approach of studying protein-coding regions, they found no differences. However, when they used their deep learning system to rank mutations according to how much they change splicing, surprising patterns appeared.</p> <p>“When we ranked mutations using our method, striking patterns emerged, revealing 39 novel genes having a potential role in autism susceptibility,” Frey said.</p> <p>And autism is just the beginning&nbsp;–&nbsp;this mutation indexing method is ready to be applied to any number of diseases, and even non-disease traits that differ between individuals.</p> <p>Dr. Juan ValcĂĄrcel JuĂĄrez, a researcher with the Center for Genomic Regulation in Barcelona, Spain, who was not involved in this research, said: “In a way it is like having a language translator: it allows you to understand another language, even if full command of that language will require that you also study the underlying grammar. The work provides important information for personalized medicine, clearly a key component of future therapies.”</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> <div class="field field--name-field-picpath field--type-string field--label-above"> <div class="field__label">picpath</div> <div class="field__item">sites/default/files/2014-12-18-machine-learning.jpg</div> </div> Thu, 18 Dec 2014 09:41:54 +0000 sgupta 6707 at Unlocking autism's code: Professor Stephen Scherer /news/unlocking-autisms-code-professor-stephen-scherer <span class="field field--name-title field--type-string field--label-hidden">Unlocking autism's code: Professor Stephen Scherer</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>sgupta</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2014-05-28T07:18:35-04:00" title="Wednesday, May 28, 2014 - 07:18" class="datetime">Wed, 05/28/2014 - 07:18</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Professor Stephen Scherer (photo courtesy the Faculty of Medicine)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/liam-mitchell" hreflang="en">Liam Mitchell</a></div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Liam Mitchell</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/top-stories" hreflang="en">Top Stories</a></div> <div class="field__item"><a href="/news/tags/medicine" hreflang="en">Medicine</a></div> <div class="field__item"><a href="/news/tags/hospital" hreflang="en">Hospital</a></div> <div class="field__item"><a href="/news/tags/health" hreflang="en">Health</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/research" hreflang="en">Research</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">New formula for identifying disorder at younger age could mean earlier therapy, better tests</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A Toronto research team has identified the formula for diagnosing autism spectrum disorder (ASD) at an earlier age. This will let patients receive therapies at an earlier age, while helping to create&nbsp; more advanced genetic diagnostic tests.&nbsp;&nbsp;</p> <p>Published recently in <a href="http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2980.html"><em>Nature Genetics</em></a>, the research unravels the autism code by creating a “genetic formula” that will help clinicians identify genetic mutations that have the highest and lowest likelihood of causing ASD.</p> <p>The work was led by molecular genetics professor <strong>Stephen Scherer</strong>, who is director of the McLaughlin Centre for Molecular Medicine at the șüÀêÊÓÆ” and director of The Centre for Applied Genomics at The Hospital for Sick Children.</p> <p>“In our new study we’ve finally discovered a unifying set of characteristics in the DNA that we can weave into a ‘genetic formula’ that helps us calculate which genetic mutations have the highest probability of causing autism, and equally important, which alterations do not have a role,” Scherer said.</p> <p>Scientists have identified around 100 genes that are linked to ASD. However, depending on how these genes mutate it may or may not lead to the disorder. Scientists needed a formula that could more accurately predict which gene permutations would cause ASD.</p> <p>Dr. <strong>Mohammed Uddin</strong>, a postdoctoral fellow on Scherer’s team, found that the key to the autism mutation code lies in recognizing small segments of genes –&nbsp;called exons – that are both “highly conserved” in human evolution and “turned on”&nbsp; during early brain development. Scherer’s team identified almost four thousand such brain exons in more than seventeen hundred different genes.</p> <p>“The timing of this gene activation is an important finding. The fact that these genes could be turned on prenatally gives us a clue as to when autism could start to develop,” said Scherer.&nbsp;</p> <p>Scherer predicts that many of the novel genes discovered by his group will eventually be found to be involved in autism, intellectual disability or other related medical conditions associated with brain development or cognition.</p> <p>“This groundbreaking work will have immediate impact on efforts to develop more accurate genetic diagnostic tests aimed at improving earlier detection and clinical decisions to begin intervention,” said Dr. Robert Ring, chief scientific officer of Autism Speaks.</p> <p>Scherer, who holds the GlaxoSmithKline-Canadian Institutes of Health Research Chair in Genetics and Genomics at U of T SickKids, recently led an international group of scientists that developed a new <a href="http://www.sickkids.ca/AboutSickKids/Newsroom/Past-News/2014/sickkids-led-researcher-team-develop-guidebook-for-autism-diagnosis.html">genetic “guidebook”</a> for autism diagnosis.<br> &nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> <div class="field field--name-field-picpath field--type-string field--label-above"> <div class="field__label">picpath</div> <div class="field__item">sites/default/files/2014-05-28-stephen-scherer-autism.jpg</div> </div> Wed, 28 May 2014 11:18:35 +0000 sgupta 6201 at For some autistic children, audio and visual don't sync /news/some-autistic-children-audio-and-visual-dont-sync <span class="field field--name-title field--type-string field--label-hidden">For some autistic children, audio and visual don't sync</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>sgupta</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2014-01-17T11:07:45-05:00" title="Friday, January 17, 2014 - 11:07" class="datetime">Fri, 01/17/2014 - 11:07</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">(photo by Andrew Plumb via Flickr)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jessica-lewis" hreflang="en">Jessica Lewis</a></div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Jessica Lewis</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/top-stories" hreflang="en">Top Stories</a></div> <div class="field__item"><a href="/news/tags/autism" hreflang="en">Autism</a></div> <div class="field__item"><a href="/news/tags/faculty-arts-science" hreflang="en">Faculty of Arts &amp; Science</a></div> <div class="field__item"><a href="/news/tags/research" hreflang="en">Research</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">Like watching a movie where the sound lags, research finds</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>If you've just loaded up a movie to watch and the actor's speaking is lagging behind their lips moving, you know the movie's audio and visual aren't synced properly. It’s distracting.</p> <p>This is what it's like for some children with autism, says a study by șüÀêÊÓÆ” psychology postdoctoral researcher&nbsp;<strong>Ryan Stevenson</strong>.</p> <p>"Our study shows that individuals with autism have difficulties processing the timing of what they hear and what they see, often reporting two events as synchronous when they are quite far out of sync," said Stevenson, who started the research while working at Vanderbilt University.</p> <p>Stevenson and his team also directly linked the ability of people with autism to process the timing between sight and sound with their abilities to perceive audiovisual speech. The people with autism who showed less precise timing between sight and sound were less likely to correctly perceive audiovisual speech, which drastically impacts their ability to communicate and have good social interactions.</p> <p>The team tested 64 children with and without autism between the ages of 6 and 18. Each child completed various tasks. In one, they were presented with a simple flash of light and a beep at varying levels of asynchrony (i.e., the flash either came before, after or at the same time as the beep). The children pressed a button indicating if what they heard and saw were synchronized. They also used an illusion called the McGurk Effect, which measured whether or not the child could perceive what they heard a speaker say and what they saw a speaker say as a single event, which indicates a high ability to perceive audiovisual speech, or as two separate events.</p> <p>"One of the primary issues that individuals with autism face is difficulty with social communication," says Stevenson. "One of the fundamental building blocks needed to have success in social communication is the ability to accurately perceive what is going on around you. If you have difficulties perceiving the world around you, it’s intuitive that you may also have difficulties interacting with that world, and the other people in it."</p> <p>Stevenson says these new insights may prove useful in designing treatments for children with autism. He notes that sensory systems are extremely adaptable, and he and his team are currently testing a new computer-based treatment for individuals with autism. The goal is to improve the sensory abilities of individuals with autism, which may lead to improved social communication abilities.</p> <p>Stevenson worked with Mark Wallace at the Vanderbilt Brain Institute in Nashville, Tennessee. Their study entitled "Multisensory Temporal Integration in Autism Spectrum" was published in <a href="http://www.jneurosci.org/"><em>The Journal of Neuroscience</em></a> on January 15. The research was funded by the United States National Institute of Deafness and Communicative Disorders.</p> <p><em>Jessica Lewis is a writer with the Faculty of Arts &amp; Science at the șüÀêÊÓÆ”.</em></p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> <div class="field field--name-field-picpath field--type-string field--label-above"> <div class="field__label">picpath</div> <div class="field__item">sites/default/files/2014-01-17-autistic-kids.jpg</div> </div> Fri, 17 Jan 2014 16:07:45 +0000 sgupta 5820 at