Donelley Centre / en Mikko Taipale has the second-best job in the world: finding cures for genetic diseases /news/mikko-taipale-has-second-best-job-world <span class="field field--name-title field--type-string field--label-hidden">Mikko Taipale has the second-best job in the world: finding cures for genetic diseases</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/taipale_1140.jpg?h=afdc3185&amp;itok=8rDFPFJ7 370w, /sites/default/files/styles/news_banner_740/public/taipale_1140.jpg?h=afdc3185&amp;itok=OZsRL39C 740w, /sites/default/files/styles/news_banner_1110/public/taipale_1140.jpg?h=afdc3185&amp;itok=HPF7RiRn 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/taipale_1140.jpg?h=afdc3185&amp;itok=8rDFPFJ7" alt="Mikko Taipale"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>lavende4</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2016-10-04T14:52:50-04:00" title="Tuesday, October 4, 2016 - 14:52" class="datetime">Tue, 10/04/2016 - 14:52</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">Mikko Taipale: “We want to democratize research in rare diseases because most of them are completely neglected” (Photo by Julia Soudat)</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-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Jovana Drinjakovic</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/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/genetics" hreflang="en">Genetics</a></div> <div class="field__item"><a href="/news/tags/donelley-centre" hreflang="en">Donelley Centre</a></div> <div class="field__item"><a href="/news/tags/cifar" hreflang="en">CIFAR</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Professor&nbsp;<strong>Mikko Taipale</strong>&nbsp;believes cures for genetic disorders already exist. We just have to find them.</p> <p>“I have the second best job in the world. The first is being an astronaut,” says Taipale, an assistant professor of molecular genetics at the University of Toronto’s Donnelly Centre. With his feet firmly planted on the ground, Taipale is finding cures for genetic diseases.</p> <p>Taipale, 39, has won an&nbsp;<a href="https://www.cifar.ca/assets/inaugural-cifar-azrieli-global-scholars-appointed/" target="_blank">inaugural $100,000 CIFAR-Azrieli Fellowship</a>. It’s awarded to 18 scientists worldwide, who are less than five years into their first academic appointments, by the Canadian Institute for Advanced Research (CIFAR). Among the other winners are οprofessors&nbsp;<strong>Natalie&nbsp;Bau</strong>&nbsp;(economics) and&nbsp;<strong>Luyi Yang</strong>&nbsp;(physics).</p> <p>“This group of phenomenal young investigators is the future of research,” said CIFAR President and CEO&nbsp;<strong>Alan Bernstein</strong>&nbsp;in the institute’s announcement.</p> <p>Taipale joined the Donnelly Centre in 2014 after a post-doctoral fellowship in the lab of Professor Susan Lindquist at the Whitehead Institute for Biomedical Research and MIT, where he studied how proteins – the end products of genes – fold into three-dimensional molecular machines. At Donnelly, he has expanded his research to a number of cellular processes that ensure proteins are properly made and working, in order to understand what makes cells healthy and how changes in protein biology cause disease.</p> <p>One of Taipale’s projects sets out to investigate rare and debilitating – but often overlooked – disorders.</p> <p>“We want to democratize research in rare diseases because most of them are completely neglected. Developing a new drug costs $1.2 billion and you cannot recover those costs if you only treat thousands, or even hundreds of patients in some cases,” says Taipale.</p> <p>A rare genetic disease occurs when a particular gene is mutated so that the protein it encodes no longer works. For example, mutations that impede the function of proteins encoded by the genes CFTR or dystrophin will cause cystic fibrosis and muscular dystrophy, respectively. Such harmful mutations run through family trees but only wreak havoc in a small number of people. That’s because we carry two copies for every gene, one inherited from each parent. If one copy of a gene is broken, its harmful effects are masked by the other working copy of the gene. It’s only when someone inherits both bad versions of the gene that they get sick.</p> <p>Unlike complex diseases such as cancer, which are caused by mutations in many genes, rare diseases are an easier problem to solve. If you could find a way to restore the broken gene’s function, you might be able to alleviate symptoms or cure the disease altogether. Still, a relatively small patient population means that the pharmaceutical industry has little incentive to invest in these diseases.</p> <p>But what if drugs already existed? What if they lurked among thousands of compounds that have already been approved or are being developed for other conditions?</p> <p>“We’re trying to completely change the way in which we study rare genetic diseases. Traditionally, these diseases are studied one at a time with multiple methods, and we want to study one thousand diseases all at once, with one or two methods” says Taipale.</p> <p>To do this, he has a collection of 1000 mutant proteins – each carrying a mutation known to cause a genetic disease. The plan is to run a battery of tests on these damaged proteins, side-by-side with their healthy counterparts. “These experiments will help us understand the underlying molecular causes of disease. Then we can use FDA-approved drugs to fix the damaged proteins. We are trying to find a disease for a drug and not a drug for a disease,” says Taipale.</p> <p>Taipale cites an example of lonafarnib, a failed cancer drug that was repurposed to treat progeria – an extremely rare condition where aging is accelerated so much that patients die of old-age complications in their teens. The drug works by reigning in the rogue progerin protein, which is the underlying cause of the disease.</p> <p>“Even if you hadn’t known anything about the molecular biology of progerin, and done a screen with FDA-approved drugs and drugs in clinical trials, you probably would have found the same compound. I have a hard time believing that out of 7000 rare diseases this would be the only one that has an existing drug that could work. Maybe we’ll be able to make a difference for one of these 1000 diseases that we study, but I have no idea which disease it will be,” said Taipale.</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> Tue, 04 Oct 2016 18:52:50 +0000 lavende4 101321 at Why we're smarter than chickens /news/why-were-smarter-chickens <span class="field field--name-title field--type-string field--label-hidden">Why we're smarter than chickens</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="2015-08-21T09:02:38-04:00" title="Friday, August 21, 2015 - 09:02" class="datetime">Fri, 08/21/2015 - 09:02</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 Johnathan Nightingale 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/jovana-drinjakovic" hreflang="en">Jovana Drinjakovic</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">Jovana Drinjakovic</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/more-news" hreflang="en">More News</a></div> <div class="field__item"><a href="/news/tags/medicine" hreflang="en">Medicine</a></div> <div class="field__item"><a href="/news/tags/health" hreflang="en">Health</a></div> <div class="field__item"><a href="/news/tags/evolution" hreflang="en">Evolution</a></div> <div class="field__item"><a href="/news/tags/donelley-centre" hreflang="en">Donelley Centre</a></div> <div class="field__item"><a href="/news/tags/blencowe" hreflang="en">Blencowe</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">Researchers at U of T’s Donnelly Centre uncover protein part that controls neuron development</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>οresearchers have discovered that a single molecular event in our cells could hold the key to how we evolved to become the smartest creatures on the planet.</p> <p>Professor<strong> <a href="http://news.utoronto.ca/pair-professors-win-john-c-polanyi-research-award">Benjamin Blencowe</a> </strong>and his team at the <a href="http://tdccbr.med.utoronto.ca/">Donnelly Centre for Cellular and Biomolecular Research</a> have determined that a small change in a protein called PTBP1 spurred the creation of neurons and fuelled the evolution of mammalian brains to become the largest and most complex among vertebrates.</p> <p>The study is published in <a href="http://www.sciencemag.org/content/349/6250/868">the August 20 issue of <em>Science</em></a>.&nbsp;</p> <p>Brain size and complexity vary enormously across vertebrates, but it is not clear how these differences came about. Humans and frogs, for example, have been evolving separately for 350 million years and have very different brain abilities. Yet scientists have shown that they use a remarkably similar repertoire of genes to build organs in the body.</p> <p>So how is it that a similar number of genes, which are also switched on or off in similar ways in diverse vertebrate species, generate a vast range of organ size and complexity?</p> <p>The key lies in alternative splicing (AS), whereby gene products are assembled into proteins, which are the building blocks of life. During AS, gene fragments called exons are shuffled to make different protein shapes. It’s like LEGO, where some fragments can be missing from the final protein shape.</p> <p>AS enables cells to make more than one protein from a single gene, so that the total number of different proteins in a cell greatly surpasses the number of available genes. A cell’s ability to regulate protein diversity at any given time reflects its ability to take on different roles in the body.</p> <p>Blencowe’s previous work showed that AS prevalence increases with vertebrate complexity. So although the genes that make bodies of vertebrates might be similar, the proteins they give rise to are far more diverse in mammals than in birds and frogs.</p> <p>And nowhere is AS more widespread than in the brain.</p> <p>“We wanted to see if AS could drive morphological differences in the brains of different vertebrate species,” says graduate student <strong>Serge Gueroussov</strong>, lead author of the study. Gueroussov previously helped identify PTBP1 as a protein that takes on another form in mammals. The mammalian form of PTBP1 is shorter because a small fragment is omitted during AS and does not make it into the final protein shape.<br> &nbsp;<br> Could this newly acquired, mammalian version of PTBP1 provide clues to how our brains evolved? PTBP1 is both a target and major regulator of AS. PTBP1’s job in a cell is to stop it from becoming a neuron by holding off AS of hundreds of other gene products.</p> <p>Gueroussov showed that in mammalian cells, the presence of the shorter version of PTBP1 unleashes a cascade of AS events, tipping the scales of protein balance so that a cell becomes a neuron.</p> <p>What’s more, when Gueroussov engineered chicken cells to make the shorter, mammalian-like PTBP1, this triggered AS events that are found in mammals.</p> <p><img alt src="/sites/default/files/2015-08-21-brain.jpg" style="width: 350px; margin: 10px 25px; height: 221px; float: right;">“One interesting implication of our work is that this particular switch between the two versions of PTBP1 could have affected the timing of when neurons are made in the embryo in a way that creates differences in morphological complexity and brain size,” says Blencowe, who is also Banbury Chair in Medical Research and a professor in the department of molecular genetics.</p> <p>(<em>Image at right: frog and human brain, to scale</em>.)</p> <p>As scientists continue to sift through countless molecular events occurring in our cells, they will keep finding clues as to how our bodies and minds came to be.</p> <p>“This is the tip of an iceberg in terms of the full repertoire of AS changes that likely have contributed major roles in driving evolutionary differences,” says Blencowe.</p> <p>(<a href="http://www.news.utoronto.ca/scientists-discover-tiny-gene-fragments-linked-brain-development-and-autism">Read more about&nbsp;Blencowe's work on AS and how it has opened new&nbsp;pathways in research into autism</a>.)</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/2015-08-21-chickens.jpg</div> </div> Fri, 21 Aug 2015 13:02:38 +0000 sgupta 7228 at