By JESS SZKLANY
Published September 10, 2020
What do a 20-year-old college student, 52-year-old mother of three and 86-year-old former Navy pilot have in common? If any one of them becomes infected with COVID-19, it is unknown whether they will be asymptomatic, spend weeks on a ventilator, or something in between.
In collaboration with the university’s Center of Excellence in Bioinformatics and Life Sciences (CBLS), researchers are trying to solve this puzzle, as well as answer other urgent questions surrounding the virus.
Since 2006, the CBLS, located on the Buffalo Niagara Medical Campus, has been at the heart of UB’s biomedical innovation efforts. It connects faculty and businesses to life sciences resources, experts, equipment, advanced computing solutions and funding that encourages translational research and fosters a path to commercialization success.
This set of resources positioned the CBLS to easily pivot when the pandemic hit.
“The CBLS was quickly able to support COVID-related research, as we have the appropriate infrastructure in place — scientific expertise, core facilities with relevant technologies and equipment, and entrepreneurial-minded industry partners,” says Smitha James, associate director for scientific operations and industry engagement in UB’s Office of Business and Entrepreneur Partnerships, which operates the CBLS.
Sequencing the viral genome
COVID-19 researchers around the world have one common goal: learning as much as possible about the virus RNA to develop treatment options and a vaccine. One UB research team is aiding this objective by sequencing the viral genome from patient samples in Western New York.
Understanding the viral genome and its function will lead to answers sought by many of the world’s top COVID-19 scientists and clinicians, such as how quickly the virus is mutating, how many strains exist and whether or not the virus is becoming more lethal or slowing down. The more researchers know about the virus at the genome level, the better prepared they are for developing drugs and treatment protocols.
“Through collaboration with Dr. Jennifer Surtees in the Department of Biochemistry and the Erie County Health Laboratory, COVID-19 viral genomes isolated from patients in Western New York were sequenced at the Genomics and Bioinformatics Core (GBC), located in the CBLS, using an illumina MiSeq sequencing platform,” says Jonathan Bard, senior programmer and bioinformatics analyst at the GBC. “Next-generation sequencing allows us to place a spotlight on each and every part of the virus genome, allowing us to look for the smallest of changes, which helps us better understand how the virus is changing over time.”
The sequencers produce raw data that bioinformatics experts like Bard rapidly reconstruct by leveraging the computational infrastructure available in the Center for Computational Research (CCR), the supercomputing facility located at the CBLS.
“We are trying to place the samples collected in Western New York on more or less of a timeline, organized by the dates we collect the sample and by the type of mutations we have seen in each virus genome. Over time, as the mutations accumulate, we can construct a ‘tree’ of how samples are related to each other. The trunk of the tree would be the very first virus sequenced, while the branches and off-shoots are strains with different mutations over the past many months,” says Bard.
The information is then integrated into public databases, where researchers around the globe work together to align data from genomes sequenced in their region with others’. This means local researchers are potentially able to locate the origins of the virus strain circulating in Western New York.
“Using location, we can measure how the virus has diverged in different areas and see when a single strain jumps from place to place, like from Wuhan to Italy to New York,” says Bard.
Predicting how COVID affects individuals
Another group of UB researchers is working toward a novel strategy for predicting how COVID-19 infections will affect individual patients, regardless of their age. The goal is for health care providers to be able to assign patient risk levels for tailored treatment options that improve patient outcomes.
“The outcome of COVID-19 is very difficult to predict,” says Jun Qu, professor in the Department of Pharmaceutical Sciences and head of the Proteomics and Bioanalysis Core (PBC) at the CBLS. “Individualizing risk prediction for positive COVID-19 patients is critical, but no reliable risk stratification tool for the outcome exists.”
The research being conducted by Qu’s team — a collaboration with Clinical Research Office Director Sanjay Sethi, professor and chief of pulmonary, critical care and sleep medicine in the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB — utilizes novel protein-measurement techniques and sophisticated mass spectrometry technologies at the PBC to draw connections between proteins from groups of patient samples.
“We are in the process of comparing the plasma proteomes from patients of different severity and outcome of COVID-19, searching for the potential group of biomarkers that could predict the outcome of the disease and, therefore, stratification and management of risks of the patients effectively,” Qu explains.
Through studying the proteins in groups of patients with different levels of severity to see if, for example, severe cases have a different effect on proteins as compared to asymptomatic cases, the team seeks to identify patterns that are closely associated with the outcomes of COVID-19. This data could then be employed for predicting disease outcomes and progression in clinics.
Qu also worked with Sriram Neelamegham, professor in the Department of Chemical and Biological Engineering, to understand the binding of proteins at the initial stage of virus invasion — a project that could help inform vaccine development and clinical intervention.
To cause infection, a virus must bind to a protein on cells in the human body. Qu and Neelamegham investigated the structure of COVID-19 proteins to determine how they bind to human proteins. This data could be invaluable to vaccine and drug developers, who must ensure that, when injected in humans, the vaccine will faithfully repeat the binding behaviors of the virus. This is how a successful vaccine produces the same immune response as it would in a real virus attack.
Supporting future innovations
To facilitate continued growth and increased new research, an incubator facility is being added within a renovated portion of the CBLS. Construction is underway, with the Incubator @ CBLS set to open at the end of the year.
The incubator will offer affordable, flexible spaces — nearly 25,000 square feet — for technology-based startups affiliated with UB and Innovation Hub partner institutions, including Roswell Park Comprehensive Cancer Center, Hauptman-Woodward Medical Research Center, the Jacobs Institute and Kaleida Health.
Renovations will add sought-after wet lab space, event space, a positive pressure cleanroom, walk-in cold rooms, emergency power and extensive shared equipment. New incubator programs will accelerate startup formation and growth.
As evidenced by COVID-19 research, the CBLS brings innovators together, supporting collaboration and ingenuity to further scientific discovery. The building renovations and programming will amplify those efforts, opening up space for UB and affiliated life sciences startups to leverage the equipment, technology, shared-use spaces and in-house expertise to create and commercialize impactful innovations into the future.
“The COVID-19 pandemic is an example of how we can quickly pivot to address a public health crisis through leveraging our experts and technology on high-priority projects,” says Norma Nowak, executive director of the CBLS. “The opening of the new incubator will create new opportunities and continue to foster collaboration and further strengthen the CBLS as a hub for life sciences innovation.”