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.
DISRUPTIVE: BIO-INSPIRED ROBOTICS features three separate interviews with (1) RADHIKA NAGPAL, (2) ROBERT WOOD, and (3) CONOR WALSHWritten on October 7th, 2015
Welcome to the second episode of my new monthly podcast series produced with Harvard’s Wyss Institute for Biologically Inspired Engineering.
DISRUPTIVE: BIO-INSPIRED ROBOTICS features three separate interviews with (1) RADHIKA NAGPAL, (2) ROBERT WOOD, and (3) CONOR WALSH. From insects in your backyard, to creatures in the sea, to what you see in the mirror, engineers and scientists at Wyss are drawing inspiration to design a whole new class of smart robotic devices
In this one, RADHIKA NAGPAL talks about her work Inspired by social insects and multicellular systems, including the TERMES robots for collective construction of 3D structures, and the KILOBOT thousand-robot swarm. She also speaks candidly about the challenges faced by women in the engineering and computer science fields.
In part two, ROBERT WOOD discusses new manufacturing techniques that are enabling popup and soft robots. His team’s ROBO-BEE is the first insect-sized winged robot to demonstrate controlled flight.
In part three, CONOR WALSH discusses how a wearable robotic exosuit or soft robotic glove could assist people with mobility impairments, as well as how the goal to create real-world applications drives his research approach.
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.
Wyss Institute for Biologically Inspired Engineering
DISRUPTIVE: CONFRONTING SEPSIS
Terrence McNally interviews Don Ingber and Mike Super
[00:04] Hello, I’m Terrence McNally and you’re listening to DISRUPTIVE the podcast from Harvard’s Wyss Institute for Biologically Inspired Engineering.
The mission of the Wyss 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.
They focus on technology development and its translation into products and therapies that will have an impact on the world in which we live. So the Wyss is not interested in making incremental improvements to existing materials and devices, but in shifting paradigms. In this episode of DISRUPTIVE, we will focus on: CONFRONTING SEPSIS
Sepsis is a bloodstream infection in which the body’s organs become inflamed and susceptible to failure. The leading cause of hospital deaths, sepsis kills at least eight million people worldwide each year.
It can be caused by 6 species of fungi and 1400 species of bacteria. Diagnosis takes two to five days, and every hour you wait can increase the risk of death by 5-9%. The treatment challenge grows more complex as the prevalence of drug-resistant bacteria increases while the development of new antibiotics lags.
“Even with the best current treatments, sepsis patients are dying in intensive care units at least 30% of the time,” says one of today’s guests, Wyss Senior Staff Scientist Mike Super.
A new device developed by a team at Wyss and inspired by the human spleen may radically transform the way we treat sepsis. Their blood-cleansing approach can be administered quickly, even without identifying the infectious agent. In animal studies, treatment with this device reduced the number of targeted pathogens and toxins circulating in the bloodstream by more than 99%.
Although we focus here on treatment of sepsis, the same technology could in the future be used for other applications, including removing microbial contaminants from circulating water, food or pharmaceutical products.
Now let’s explore the development process with Mike Super and Wyss Founding Director, Don Ingber.
[02:25] Ingber leads the Biomimetic Microsystems platform at Wyss in which micro-fabrication techniques from the computer industry are used to build functional circuits with living cells as components. He’s authored more than 400 publications and over 100 patents.
The seeds of Wyss’s therapeutic sepsis device go back over twenty years. I ask Don to talk about some of the earlier explorations and findings that laid the foundations for the current work.
[02:51] I was interested in mechanics and biology, this idea that mechanical forces are as important as chemicals and genes, and that the shape of the cell is important. To get at testing that, I come up with the idea of using little magnetic particles that I would coat with molecules that would bind to specific receptors on cells.