DISRUPTIVE #7: FISSEQ – Fluorescent In Situ RNA Sequencing
Hello, I’m Terrence McNally and you’re listening to DISRUPTIVE the podcast from Harvard’s Wyss Institute for Biologically Inspired Engineering.
One of today’s guests, George Church, has made the point that as medicine moves from very blunt instruments – where you had to open up a chest all the way, for example, or had to use molecules that would hit almost every part of your body – now molecules can find one base pair out of six billion and change it – He says we need observational tools that can deal with that high level of resolution and comprehensiveness.
And we’re going to talk about one such tool. Fluorescent in situ RNA sequencing – F-I-S-S-E-Q – or FISSEQ.
Working copies of active genes — called messenger RNAs or mRNAs — are strategically positioned throughout living tissues, and their location often helps regulate how cells and tissues grow and develop. Until recently, to analyze many mRNAs simultaneously, scientists had to grind cells to a pulp, which left them unable to pinpoint where those mRNAs actually sat within the cell.
Now a team at the Wyss Institute and Harvard Medical School has developed a new method that allows scientists to pinpoint thousands of mRNAs and other types of RNAs at once – in intact cells.
FISSEQ could lead to earlier cancer diagnosis, help biologists better understand embryonic development, and even help map the neurons of the brain.
I’ll talk with George Church, Wyss Core Faculty member and co-founder of ReadCoor, the startup that will bring FISSEQ to market; Wyss lead senior scientist, Rich Terry, President, Co-Founder, and CTO of ReadCoor; and Shawn Marcell, Wyss Entrepreneur-in-Residence and founding Chairman/CEO of ReadCoor.
The mission of the Wyss Institute is to: Transform healthcare, industry, and the environment by emulating the way nature builds.
Our bodies — and all living systems — accomplish tasks far more sophisticated and dynamic than any entity yet designed by humans.
By emulating nature’s principles for self-organizing and self-regulating, Wyss researchers develop innovative engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. [02:06]
George Church is Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT. He’s Director of the U.S. Department of Energy Center on Bioenergy at Harvard and MIT and director of the NIH Center for Excellence in Genomic Science at Harvard. He has co-founded a number of companies, including ReadCoor.
Church earned a bachelor’s degree from Duke University in two years and a PhD from Harvard. Honors include election to the National Academy of Sciences and the National Academy of Engineering. He has coauthored hundreds of scientific papers, more than sixty patents, and the book, “Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves.” [02:41]
To set the context for this episode, George Church offers an overview of the evolution of sequencing technology –
Church: It dates back at least to the ’60s when RNA sequencing and protein sequencing were the main ways of getting insight. In the mid-’70s, ways to do DNA sequencing based on electrophoresis came into play. Those were automated and made less radioactive, more fluorescent. In the ’80s and ’90s, it switched from slab electrophoresis, capillary electrophoresis. None of these scaled particularly well.
Welcome to DISRUPTIVE the podcast from Harvard’s Wyss Institute for Biologically Inspired Engineering.
In this episode of DISRUPTIVE, we will focus on a cancer vaccine and hydrogel drug depots – both being developed by Wyss Founding Core Faculty Member, DAVE MOONEY. Mooney says the human immune system is the most efficient weapon on the planet to fight disease. Cancer, however, resists treatment and cure by evading the immune system. Unlike bacterial cells or viruses, cancer cells belong in the body, but are simply mutated and misplaced. Scientists have been trying to develop vaccines that provoke the immune system to recognize cancer cells as foreign and attack them. The approach developed by Mooney’s group, in which they reprogram immune cells from inside the body using implantable biomaterials, appears simpler and more effective than other cancer vaccines currently in clinical trials. In one study, 50% of mice treated with two doses of the vaccine — mice that would have otherwise died from melanoma within about 25 days — showed complete tumor regression. On a second front, when it comes to delivering drugs or protein-based therapeutics, doctors often give patients pills or inject the drug into their bloodstream. Both are inefficient methods for delivering effective doses to targeted tissues. Mooney and his team at Wyss are taking a new approach using biocompatible and biodegradable hydrogels. They’ve developed a gel-based sponge that can be molded to any shape, loaded with drugs or stem cells, compressed to a fraction of its size, and delivered via injection. Once inside the body, it pops back to its original shape, gradually releases its payload, and safely degrades. After we explore both of these exciting projects with Mooney, we take a closer look at the process of translation of hydrogel technology into products and therapies with Chris Gemmiti, a business development lead at Wyss.
Free Forum Q&A – TIM RYAN Congressman, author, A MINDFUL NATION: How a Simple Practice Can Help Us Reduce Stress, Improve Performance, Recapture American Spirit & WINIFRED GALLAGHER RAPT: Attention and the Focused LifeWritten on April 2nd, 2015
TIM RYAN (originally aired August 2012)
WINIFRED GALLAGHER (originally aired May 2009)
“My experience is what I agree to attend to.” — William James
This week we focus on mindful attention – hailed by ancient spiritual traditions and modern neuroscience alike as one of the keys to the quality of our lives.
In the first half, I’ll be joined by Ohio Congressman TIM RYAN, who offers a radical solution to the stresses and problems that face Americans today — radical in its original meaning of having to do with roots of things. He has written a book, A MINDFUL NATION: How a Simple Practice Can Help Us Reduce Stress, Improve Performance, and Recapture the American Spirit. Ryan has a daily practice of mindful meditation and now he’s advocating that the spread of similar practices could help heal us, not just as individuals but as a nation. And his book is filled with examples of how mindfulness is already being successfully applied in education, healthcare, even the military.
Then I’ll speak with bestselling author, WINIFRED GALLAGHER about her book, RAPT: Attention and the Focused Life. In it, she argues that “”The skillful management of attention is the… key to improving virtually every aspect of your experience, from mood to productivity to relationships.” Gallagher came to appreciate this while fighting a fairly advanced form of cancer. Determined not to let her illness “monopolize” her attention, she made a conscious choice to look “toward whatever seemed meaningful, productive, or energizing and away from the destructive, or dispiriting.” Her experience of the world was transformed, and she set out to learn more about the science of attention as well as what we can do to cultivate it.
Here’s one big tip based on neuroscience: GALLAGHER recommends starting your workday concentrating on your most important task for 90 minutes. At that point, your brain may need a break But don’t let yourself get distracted by anything else during that first hour and a half, because it can take the brain 20 minutes to reboot after an interruption.