Since the novel and fast-spreading SARS-CoV-2 coronavirus first upended life in the United States and around the world, scientists at Boston University's National Emerging Infectious Diseases Laboratories (NEIDL) have dropped nearly every other research project to focus on understanding and combating the virus. Now, BU scientists have received nearly $1.9 million in new funding from the Massachusetts Consortium on Pathogen Readiness (MassCPR) to further advance coronavirus research-much of that work made possible by the NEIDL's ability to safely house and work with live copies of the SARS-CoV-2 virus.
All told, on May 13 MassCPR announced it has awarded $16.5 million to 62 coronavirus research projects, many of those funds going to research teams in Greater Boston. Much of the funded work will be done in collaboration with scientists at the NEIDL, one of only a handful of facilities in Massachusetts currently capable of working with live, patient-derived samples of the coronavirus. MassCPR-which first convened on March 2, 2020-is buoyed by $115 million in funding, spread over the next five years, from Evergrande Group, a Fortune Global 500 company in China. Participating research collaborators include scientists and clinicians from Harvard, Massachusetts Institute of Technology, BU, Tufts University, University of Massachusetts, and local biomedical research institutes, biotech companies, and academic medical centers.
Of the MassCPR funding that will support coronavirus research at BU, the largest chunk-a $600,000 award-stemmed from a conversation that Ronald Corley, microbiologist and director of the NEIDL, had with MassCPR about expanding NEIDL's bandwidth.
"Everyone who is currently in the NEIDL as an investigator has their own research programs that they support with their own funding mechanisms," Corley says. "So if someone else has really good [coronavirus research] ideas, and they can't collaborate with one of our investigators, they are out of luck. Our bandwidth, right now, is defined by what individual investigators in the building can do, but we recognize that there are a lot more meritorious ideas than we can possibly handle at this point in time. So, this [$600,000] funding will help the NEIDL hire additional scientific personnel to expand the NEIDL's research footprint and allow us to work with other investigators to bring these ideas to the [lab] bench."
Aside from that funding, which will support a broad number of future projects at the NEIDL, another roughly $1.3 million in awards has gone directly to BU principal investigators for SARS-CoV-2 research that's already underway.
Modeling coronavirus infections in lung organoids
Mohsan Saeed, a NEIDL biochemist and virologist is teaming up with Darrell Kotton, director of the Center for Regenerative Medicine (CReM) at BU's Medical Campus, to model COVID-19 infections in stem cell-derived human lung organoids. With help from the CReM team, Kotton, who has been serving on the front lines as an attending physician to COVID-19 patients in the medical intensive care unit at Boston Medical Center (BMC), BU's teaching hospital, will focus on scaling up production of stem cell-derived lung organoids to share those tissues with MassCPR researchers that seek to model COVID-19 infections or screen promising drug candidates.
In partnership with Saeed at the NEIDL, and with the support of $200,000 in MassCPR funding, Kotton's team will infect human lung organoids with SARS-CoV-2 and carefully analyze the molecular and genetic pathways that COVID-19 infection employs to spread through and overwhelm human lung tissue. Saeed, who specializes in the study of lung infections, says the research-seeking to discover which cell proteins are cleaved by the SARS-CoV-2 virus as it hijacks a cell-could help uncover new drug targets that would disrupt the SARS-CoV-2 virus from successfully infecting and spreading in humans.
Better, faster COVID-19 testing thanks to machine learning
Another CReM scientist, George Murphy, has received nearly $300,000 in MassCPR funds to develop better and faster COVID-19 testing. In mid-March, Murphy-working closely with Christopher Andry, BU/BMC chief of pathology and laboratory medicine, and dozens of volunteer scientists and lab technicians from across BU's Medical Campus-helped rapidly convert part of the CReM from a tissue engineering facility into a full-scale, in-house COVID-19 testing center amidst test kit shortages and delays from state and federal agencies. Racing against the blossoming number of coronavirus infections in the city of Boston, Murphy and Andry's team devised a unique and FDA-authorized test to get around supply chain barriers that blocked them from accessing traditional COVID-19 tests, and began processing same-day testing for all BMC patients suspected of COVID-19 infection.
Now, Murphy and Andry are spearheading a new project alongside CReM faculty researchers Kim Vanuytsel and Ruben Dries. With the new MassCPR funding, they hope to reduce the 3 percent false negative average associated with current COVID-19 tests by developing a machine learning algorithm that can more accurately-and more quickly-interpret test results than human experts. The team is also developing new methods for pooling samples to increase testing speed, and creating miniaturized versions of the testing process that require less equipment and human intervention.
Drug candidate screening and making SARS-CoV-2 research more accessible
Almost $200,000 in MassCPR funding has also been awarded to NEIDL virologist Elke Mühlberger, who switched gears from studying hemorrhagic fevers like Ebola to conduct coronavirus research in collaboration with NEIDL scientists and other MassCPR investigators. At the NEIDL, Mühlberger and her team will infect cell cultures with SARS-CoV-2 and carry out experiments and drug candidate evaluations in collaboration with MassCPR researchers who do not themselves have access to a laboratory capable of working with the live SARS-CoV-2 virus, which requires a Biosafety Level 3 (BSL-3) or higher containment environment.
Typically, Mühlberger's team handles some of the world's most lethal diseases, like Ebola or Marburg fevers, inside one of the NEIDL's Biosafety Level 4 (BSL-4) laboratories, which have the highest possible level of biosafety containment used for infectious agents that pose especially high risk to humans. BSL-4 is a full step of containment above the required BSL-3 that's needed for working with live copies of SARS-CoV-2.
But the personal protection equipment that researchers must wear for BSL-3 work is the same gear that hospital clinicians are direly short of right now. So, at the NEIDL, one of the few research facilities in the United States to have both BSL-3 and BSL-4 laboratories, many researchers-like Mühlberger's team-are choosing to handle the SARS-CoV-2 virus while each wearing full, airtight biocontainment suits connected to an air hose, taking the virus up to the BSL-4 level of containment.
Inside a BSL-4 lab, Mühlberger's team, which also recently received a $100,000 Fast Grant for their SARS-CoV-2 work, will modify the virus to enable safer versions of it to be used by researchers at lower biocontainment laboratories-because the more scientists that can safely do coronavirus research, the faster the pandemic can be brought under control. Coronaviruses like SARS-CoV-2 have extremely long genomes, making genetic modifications and cloning challenging. But Mühlberger has plenty of experience genetically modifying Ebola and Marburg viruses. To make it all happen, she is teaming up with her longtime collaborator and coronavirus expert Volker Thiel of University of Bern, Switzerland, who has received $60,000 in additional MassCPR funding.
Screening thousands of compounds in search of new COVID-19 treatments
Inside another BSL-4 lab at the NEIDL, microbiologist Robert Davey's ongoing coronavirus work will be further supported with $400,000 in new MassCPR funding. Davey's team specializes in pitting thousands upon thousands of drugs-small molecules made of different chemical concoctions-against lab cultures of cells infected with viruses, allowing them to rapidly detect which drugs are most effective at halting or reducing infection.
Since getting started in March, they've already made progress on their COVID-19 research, leveraging glowing antibodies to get eyes on the SARS-CoV-2 virus' whereabouts inside the cells it infects. Now, the team is screening the first group of drug compounds-of which they eventually plan to test more than 20,000 potential therapeutics-to see if they are able to halt or block COVID-19 infections.
Understanding why the novel coronavirus hits some harder than others
Across the BU Medical Campus quad, Joshua Campbell, a biostatician and cancer researcher, is pivoting to study SARS-CoV-2 with a team of clinical biologists-including co-principal investigators and BU faculty researchers Jennifer Beane, Elizabeth Duffy, and Sarah Mazzilli-to better understand the genetic factors that make some people more likely to experience severe COVID-19 infections than others.
Specifically, with the support of $185,000 in new MassCPR funding, they will research how genes are expressed across different cell types in the lungs, and how gene expressions vary across people of different ages and demographic backgrounds, and who have different environmental exposures and lung diseases. To do so, they will establish a BU-BMC biobank to collect samples from COVID-19 patients of a broad range of health histories, ethnicities, and socioeconomic statuses. Campbell and his team are in touch weekly with researchers from the NEIDL and the CReM, and will likely partner with NEIDL virologists to complete some lab work as they get further along in their SARS-CoV-2 research.
"The NEIDL was built to be able to study emerging infectious diseases and respond to national emergencies," says Corley, NEIDL's director. "This pandemic … [we've witnessed] the value of having a facility like the NEIDL and all the expertise that we've brought into it."
MassCPR will hold its first public briefing, via YouTube livestream, on Friday, May 15, 2020 at 8 am ET to discuss the progress its collaborators have made over the last few months. During the briefing, Corley will give a short presentation on the NEIDL's efforts.
