An international, multi-institutional team of researchers led by synthetic biologist James Collins, Ph.D. at the Wyss Institute for Biologically Inspired Engineering at Harvard University, has developed a low-cost, rapid paper-based diagnostic system for strain-specific detection of the Zika virus, with the goal that it could soon be used in the field to screen blood, urine, or saliva samples.
“The growing global health crisis caused by the Zika virus propelled us to leverage novel technologies we have developed in the lab and use them to create a workflow that could diagnose a patient with Zika, in the field, within 2-3 hours,” said Collins, who is a Wyss Core Faculty member, and Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at the Massachusetts Institute of Technology (MIT)’s Department of Biological Engineering.
It’s estimated that as many as a million Americans suffer from inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease, which cause mild to severe symptoms that at best can be managed and at worst lead to life-threatening complications.
While abnormal immune responses are largely responsible for these diseases, issues relating to gut microbiome, intestinal epithelial cells, immune components, and the gut’s rhythmic peristalsis motions can also contribute to and exacerbate symptoms. But until now, scientists have been hard pressed to develop new therapies for treating IBDs because they could not replicate the human gut microenvironment in the laboratory.
On Monday, the Wyss Institute for Biologically Inspired Engineering at Harvard University announced that its team had created a model of human intestinal inflammation and bacterial overgrowth in a human-gut-on-a-chip. The team, co-led by Wyss Institute Founding Director Donald Ingber and core faculty member James Collins, leveraged the institute’s proprietary human-organs-on-chips technology to microengineer the model.
“There is much to be learned about IBD, as well as how antibiotics impact the microbiome,” said Collins, the Termeer Professor of Bioengineering in the Department of Biological Engineering and Institute for Medical Engineering & Science at the Massachusetts Institute of Technology. “This technology enables one to study in an isolated and controlled manner the complexity of the microbiome and the role different microbial species play in health and disease. It is therefore a highly valuable platform for discovery and clinical translation efforts.”...
t happens over and over again with new science. A discovery prompts crazy hype and massive investment that the data aren’t ready to support. A crash ensues, backers lose millions, egos are bruised—yet the pioneers slowly trudge forward. They regroup, away from the limelight, and try to learn from failure.
When it comes to synthetic biology—a method of modifying the genes of living organisms to effectively change what they do—James Collins knows this story better than most. He’s an MIT professor who helped found the field nearly two decades ago. He’s seen the hype, when investors placed huge bets on startups aiming to produce clean energy on a large scale; the crash, when many of those companies were wiped out and scientists fled back to academia; and the pivot, when the surviving companies shifted their sights elsewhere.
“I think we’ve recovered now, as a field,” he says.
Gone are the days when a bevy of high-profile startups like Sapphire Energy, Solazyme, and J. Craig Venter’s LS9 offered hopes of renewable, eco-friendly fuels made by engineered algae. In their wake is diversification: Sapphire, for instance, has made a strategic pivot into things like food additives, cosmetics, and nutraceuticals. But from Collins’s vantage point, something else has happened. The “clinical space,” he says, has become a dominant focus for synthetic biologists—meaning tools that could be used for medical research, diagnostics, or even “living” therapeutics like the ones Cambridge, MA-based Synlogic, a startup from Collins’s lab, is trying to develop.
Collins (pictured above) is a New York-New England hybrid. He was born in the Bronx before moving first to Bellerose, in the outskirts of Queens, and later, after he finished elementary school, to New Hampshire. He used to have a strong New York accent and, as a Queens guy, was a fan of the Jets, Mets, and Nets. (Former Nets small forward William “Billy” Schaeffer, who also grew up in Bellerose, would shoot hoops nearby.) Now that Big Apple accent is largely gone (“I joke that I’ve got a New York attitude but not a New York accent,” he says) and Collins shows a fierce allegiance to all teams Boston. He even threw out the first pitch at a Red Sox game in 2008 at Fenway Park....
—Cool technology. Now, what to we do with it? Atlas Venture’s Peter Barrett and Ankit Mahadevia were interested in MIT professor Jim Collins and protégé Timothy Lu’s latest work. The synthetic biology specialists had two things cooking: a tools platform to “rewire organisms,” and an idea for engineered microbes that could serve as living drugs or diagnostics. Mahadevia’s response: “We really want to do something with you guys, we just don’t know what.”
A month later, Atlas decided no to the tools, and yes to the living drugs. But how to use them? Collins’s preference—wiping out infectious diseases, like a cholera infection. Mahadevia’s response: “We still want to do something with you guys, we just don’t know what.”
It took a suggestion from Atlas entrepreneur-in-residence Dean Falb to figure out what to do. He showed Collins a list of 12 rare genetic metabolic disorders, all of which Collins had never heard of. The microbes made sense here—they could either make a metabolite that is missing, or break down a toxic one. The medical need is significant, and Synlogic could run small, inexpensive clinical trials for it.
“I thought this was brilliant,” Collins said. Synlogic is now targeting phenylketonuria and urea cycle disorders....
The first case of the Ebola outbreak currently ravaging West Africa appeared in Guinea in December 2013. But it wasn’t until March 22, 2014, that scientists finally confirmed the virus as Ebola. By that point, 49 people had already died.
Why did it take so long? Partly because confirming the diagnosis required that epidemiologists fly from Europe to Africa, collect blood samples, fly back to Europe, and analyze them in sophisticated labs.
Now a team of biologists at BU, led by Professor James Collins (BME, MSE, SE), has created a new tool that could provide a quick, cheap way to perform sophisticated lab analyses and diagnostics in the field, and may also offer a way to speed science in the lab. The tool, called a paper gene circuit, takes biological reactions out of cells and puts them onto a piece of paper. It is described in the November 6, 2014, issue of Cell.
“This could really be a game-changer for a lot of applications, including diagnostics,” says Collins, who is also a core faculty member at Harvard’s Wyss Institute. “You can literally carry this in your pocket and run an experiment in the field without any additional equipment.”...
At the heart of synthetic biology is the assembly of genetic components into “circuits” that perform desired operations in living cells, with the long-term goal of empowering these cells to solve critical problems in healthcare, energy, the environment and other domains, from cancer treatment to toxic waste cleanup. While much of this work is done using bacterial cells, new techniques are emerging to reprogram eukaryotic cells—those found in plants and animals, including humans—to perform such tasks.
To engineer useful genetic circuits in eukaryotic cells, synthetic biologists typically manipulate sequences of DNA in an organism’s genome, but Assistant Professor Ahmad “Mo” Khalil (BME), Professor James J. Collins (BME, MSE, SE) postdoctoral fellow Albert J. Keung (BME) and other researchers at Boston University’s Center of Synthetic Biology (CoSBi) have another idea that could vastly increase their capabilities. Rather than manipulate the DNA sequence directly, the CoSBi engineers are exploiting a class of proteins that regulate chromatin, the intricate structure of DNA and proteins that condenses and packages a genome to fit within the cell. These chromatin regulator (CR) proteins play a key role in expressing—turning on and off—genes throughout the cell, so altering their makeup could provide a new pathway for engineering the cell’s genetic circuits to perform desired functions....
Professor James J. Collins (BME, MSE, SE) has been elected to the National Academy of Sciences(NAS), one of the highest honors in science and technology, in recognition of his distinguished and continuing achievements in original research.
Collins, who is one of the founders of the field of synthetic biology, joins Boston University’s seven other NAS members, a group that includes President Robert A. Brown, Nobel Prize–winning theoretical physicist Sheldon Glashow, BU’s Arthur G. B. Metcalf Professor of Mathematics and Science, and Nancy Kopell, a William Fairfield Warren Distinguished Professor. The NAS, a private, nonprofit society of distinguished scholars, is charged with providing independent, objective advice to the nation on science and technology. Collins is one of 84 new members and 21 foreign associates.
“We are thrilled to learn of Jim’s election to the National Academy of Sciences,” said Jean Morrison, University provost and chief academic officer. “This is one of the most significant honors for a scientist, and Jim is well deserving of this recognition. Jim’s pathbreaking research in synthetic and systems biology, with a particular focus on antibiotics, has set him apart as one of the world’s top researchers—and we are extraordinarily proud to have him as a member of the BU faculty.”...