Tuesday, July 14th, 2020

Time	Event
3:15p	MIT team collaborates with 3M to develop rapid Covid-19 test Hadley Sikes, an associate professor of chemical engineering at MIT, has been working for years with her team on the technology they’re adapting to create a Covid-19 test with rapid results. Moving beyond lab prototypes and into manufacturing the diagnostics on a large scale, however, is new territory. 3M is collaborating with the Sikes Lab to jointly develop the test, including establishing novel processes for scaling it. They will determine whether the test renders highly accurate results within 10 minutes, and if it is feasible to mass manufacture. “What amazes me about Hadley is her ability to use incredibly smart science to engineer a solution to a real-world problem, and take that solution all the way to translation at such a rapid pace, considering materials, cost analysis, and even manufacturing in true chemical engineering spirit,” says Paula Hammond, the David H. Koch Chair Professor of Engineering and head of the Department of Chemical Engineering. “Even as much of the world was forced to a halt, the Sikes Lab has never stopped innovating and was committed to refining their technology toward Covid-19 testing. We welcome this collaboration with 3M and what the partnership will make possible.” The National Institutes of Health selected the rapid Covid-19 test for accelerated development and commercialization support, after rigorous review by an expert panel. The test is in the Rapid Acceleration of Diagnostics Tech (RADx Tech) program, an aggressively paced Covid-19 diagnostics initiative from the NIH’s National Institute of Biomedical Imaging and Bioengineering. “We are excited to collaborate with Professor Hadley Sikes and the team at MIT. Our approach is ambitious, but our collective expertise can make a difference for people around the world, so we owe it to ourselves and society to give it our best effort,” says John Banovetz, 3M senior vice president for innovation and stewardship and chief technology officer. “This is another step demonstrating 3M’s leadership in the fight against Covid-19. We are seeking to improve the speed, accessibility, and affordability of testing for the virus, a major step in helping to prevent its spread.” Sikes saw room to innovate in the field of coronavirus testing, as the RNA tests in widespread use can take days to get results from nasal swabs and have been difficult to scale in the United States. The rapid test being developed by the Sikes Lab and 3M is based on binding proteins, and would be available at much lower cost. “Ours is a test for the proteins of the virus rather than its genetic material, and you don’t need to send a sample to the lab for processing,” she says. “Our goal is that someone with minimal training could perform the test within minutes.” RNA tests being the norm has presented challenges and a bottleneck for the team, as biorepositories and reference specimens are still not set up for protein tests. The work aimed at getting the test from lab to market has been unusual. MIT’s labs had closed in March along with the campus, but the Sikes Lab remained open on a limited basis with support from the Department of Chemical Engineering. Eric Miller, a postdoc who helped develop the technology while completing his PhD, spent long hours in the lab engineering reagents that capture and label SARS-CoV-2 proteins. Reagents prepared at MIT were overnighted to Sikes’ lab in Singapore, where she is a principal investigator in the Antimicrobial Resistance Interdisciplinary Research Group (AMR IRG), co-led by professors Peter Preiser of Nanyang Technological University and Pete Dedon of MIT, at Singapore-MIT Alliance for Research and Technology (SMART). Lab members in SMART and at MIT worked together to build prototype tests and develop user-friendly procedures. At MIT, the Deshpande Center for Technological Innovation, the Technology Licensing Office, and the Office of Strategic Transactions worked with Sikes to establish an agreement with 3M, bringing an understanding of the commercialization process with companies and “speaking their language,” she says. “Typically, it would take three to six months of negotiations to close an agreement, but everyone working on this at MIT and 3M worked 'round the clock to make it happen in 10 days,” says Leon Sandler, executive director of the Deshpande Center. “We all felt the urgency of fast-tracking the project to have a chance of getting the test out there during this public-health crisis.” Sikes’ tests had already been successful in detecting identified markers for malaria, tuberculosis, and dengue before the coronavirus outbreak. The binding proteins in her test attach to coronavirus proteins and enable detection by associating a color change with their presence. Conceptually, it is similar to an over-the-counter pregnancy test, though the format and components differ in ways that make it more scalable. The Covid-19 test would not need to be administered in a medical setting. 3M’s diverse technology and manufacturing capabilities were an ideal match for development and mass manufacturing of this new kind of paper-based diagnostic. The company produces 50 million N95 respirators a month in the United States, and has doubled global N95 respirator production globally. Pending validation of the test, the goal of the Sikes Lab, 3M, and RADx is to produce millions of the affordable, accurate tests each day in the United States. With operations across the globe, 3M could eventually build up manufacturing capacity to supply tests around the world. Sikes stressed the enormity of the team effort across organizations, which included 15 researchers in her labs, with others at SMART AMR IRG pitching in; more than 30 experts at 3M; about a dozen at NIH RADx; many staff members at MIT; and Deshpande Center “Catalyst” mentors and their networks in industry. “It’s a rare collaboration of government, industry, and university to innovate at a rapid pace in this pandemic,” she says. “Our groups and many others across the globe are doing our best to rise to the daunting challenge of swiftly adapting and deploying new technologies to increase Covid-19 testing.” This research is being funded by MIT’s Deshpande Center, SMART, and the NIH. (Comment on this)
3:55p	Findings weaken notion that size equals strength for neural connections Learning, memory, and behavioral disorders can arise when the connections between neurons, called synapses, do not change properly in response to experience. Scientists have studied this “synaptic plasticity” for decades, but a new study by researchers at MIT’s Picower Institute for Learning and Memory highlights several surprises about some of the basic mechanisms by which it happens. Getting to the bottom of what underlies some of those surprises, the research further suggests, could yield new treatments for a disorder called Fragile X that causes autism. Two classic forms of synaptic plasticity are that synapses either get stronger or weaker and that the tiny spine structures that support them get bigger or smaller. For a long time, the field’s working assumption has been that these functional and structural changes were closely associated: Strengthening went along with an increase in spine size and weakening preceded spine shrinkage. But the study published in Molecular Psychiatry adds specific evidence to support a more recent view, backed by other recent studies, that those correlations are not always true. “We saw these breakdowns of correlation between structure and function,” says Mark Bear, Picower Professor in the Department of Brain and Cognitive Sciences and senior author of the study. “One conclusion is you can’t use spine size as a proxy for synaptic strength — you can have weak synapses with big bulbous spines. We are not the only ones to make this case, but the new results in this study are very clear.” The study’s co-lead authors are former lab members Aurore Thomazeau and Miquel Bosch. To conduct the study, the team stimulated plasticity via two different neural receptors (called mGluR5 and NMDAR) under two different conditions (neurotypical rodents and ones engineered with the mutation that causes Fragile X). In Fragile X, Bear’s lab has found the lack of the protein FMRP leads to excess synthesis of other proteins that cause synapses to weaken too much in a brain region called the hippocampus, which is a crucial area for memory formation. The first surprise of the study was that activating mGluR5 receptors induced the weakening, called long-term depression (LTD), but did not lead to any spine shrinkage in either Fragile X or control mice for at least an hour. In other words, the structural change that was assumed to go along with the functional change didn’t actually occur. In the NMDAR case, the two forms of plasticity did occur together, both in control and Fragile X rodents, but not without a few more surprises lurking just beneath the surface that further dissociated functional and structural plasticity. When the team blocked a flow of ions (and therefore electric current) in the NMDAR synapses, that only prevented the weakening, not the shrinking. To prevent the shrinking in control rodents, the researchers had to do something different: inhibit protein synthesis either directly or by inhibiting a regulatory protein called mTORC1. “It was quite amazing to us,” Bear says. “We are following up on that aggressively to better understand that signaling.” If several of the surprises in the study are disruptive, Bear said, another one may provide new hope for treating Fragile X. That’s because while Bear’s lab has focused on intervening in the mGluR pathway to treat Fragile X, the new experiments involving NMDAR may reveal an additional avenue. When the team tried to prevent spines from shrinking via NMDAR in Fragile X rodents by inhibiting protein synthesis or mTORC1 (like they did in the controls), they found it didn’t work. It was as if there was already too much of some protein that promotes the shrinkage. The team was even able to replicate this Fragile X phenomenon in the controls by first stimulating mGluR5 — and an ensuing excess of protein synthesis — and then following up with the NMDAR activation. As a nod to both the mystery and the disorder, Bear has begun to refer to this conjectured potential shrinkage-promoting molecule as “protein X.” “The question is what is protein X,” Bear says. “The evidence is quite strong that there is a rapidly turned over protein X that is wreaking havoc in Fragile X. Now the hunt is on. We’ll be really excited to find it.” In addition to Thomazeau, Bosch and Bear, the paper’s other authors are Sofia Essayan-Perez, Stephanie Barnes, and Héctor de Jesús-Cortés. A Beatriu de Pinos fellowship, the FRAXA Foundation, a Marie Curie Reintegration Grant, the U.S. National Institutes of Health and the JPB Foundation supported the research. (Comment on this)

<< Previous Day

2020/07/14 [Calendar]

Next Day >>