Until recently, to analyze many mRNAs simultaneously, scientists had to grind cells to a pulp, which left them unable to pinpoint those mRNAs within the cell. Developed by a team at the Wyss and Harvard Medical School, FISSEQ allows scientists to pinpoint thousands of mRNAs and other types of RNAs at once in intact cells, and stands to revolutionize clinical diagnostics and drug discovery.
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.
Hello, I’m Terrence McNally and you’re listening to Disruptive, the podcast from Harvard’s Wyss Institute for biologically inspired engineering. In early May, a low cost, rapid, paper-based diagnostic system for strain specific detection of the Zika virus was introduced by an international consortium of researchers led by synthetic biologist James Collins with the goal that it could soon be used in the field to screen blood, urine or saliva samples.
The core of the test kit is a piece of paper that changes color in the presence of Zika virus RNA and produces results in two to three hours. Much faster and cheaper than the PCR test used now according to Collins, a Wyss core faculty member – and it should cost less than a dollar per test adds University of Toronto biochemist Keith Pardee.
I’m going to speak with both of them about the real time story of a crisis
inciting innovation. How a team from a number of different institutions came together, and in a matter of six weeks developed a new approach to detection and designed a system to deploy in the face of future pandemics. Collins says, in response to an emerging outbreak, a custom tailored diagnostic system could be ready for use within one week’s time. We’ll explore how they did it, what they’ve learned and what this might mean for the future.
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.
In addition to leading the Living Cellular Devices and cellular devices platform at the Wyss, Jim Collins is the Termeer professor of medical engineering and science and professor of biological engineering at MIT. He’s a member of the Harvard MIT health sciences and technology faculty and an institute member of the Broad Instiute of MIT and Harvard.
Collins received a BA in physics from Holy Cross and a PHD in medical engineering from Oxford. A Rhodes Scholar, a MacArthur Fellow and a winner of the National Institutes of Health Directors Pioneer Award. Jim is one of the founders of synthetic biology as well as a pioneering researcher in systems biology and his engineering ranges from the physical scale of wearable medical devices to that of molecules.
Collins says he found early inspiration both in the space program and much closer to home.
I was born and grew up initially in New York City. My dad was an electrical engineer who had worked in the aviation industry so he did work for NASA, he did work for the military, he did work for a number of companies building planes. My mom was a math teacher.
DISRUPTIVE – the podcast from Harvard’s Wyss Institute for Biologically Inspired Engineering.
We’re learning to take advantage of properties of DNA that have served nature well- but in ways nature may have never pursued. We build with it. We tap its capacity to carry information to enhance our ability to explore the inner life of cells.
In this episode, Wyss faculty members William Shih, Wesley Wong and Peng Yin share what it’s like being on the frontier of science, explain how and why they program DNA, and consider potential applications of their work.
I’m excited to offer the first episode of DISRUPTIVE, my new monthly podcast series produced with Harvard’s Wyss Institute for Biologically Inspired Engineering. The mission of the Wyss Institute is to: Transform healthcare, industry, and the environment by emulating the way nature builds, with a focus on technology development and its translation into products and therapies that will have an impact on the world in which we live. Their work is disruptive not only in terms of science but also in how they stretch the usual boundaries of academia.
In this inaugural episode, Wyss core faculty members Pamela Silver and George Church explain how, with today’s technology breakthroughs, modifications to an organism’s genome can be conducted more cheaply, efficiently, and effectively than ever before. Researchers are programming microbes to treat wastewater, generate electricity, manufacture jet fuel, create hemoglobin, and fabricate new drugs. What sounds like science fiction to most of us might be a reality in our lifetimes: the ability to build diagnostic tools that live within our bodies, find ways to eradicate malaria from mosquito lines, or possibly even make genetic improvements in humans that are passed down to future generations. Silver and Church discuss both the high-impact benefits of their work as well as their commitment to the prevention of unintended consequences in this new age of genetic engineering.