Release Date: September 15, 2020
BUFFALO, N.Y. — Jennifer Surtees is a biochemist at the University at Buffalo. For more than two decades, her research has focused on genome stability and how mutations threaten that stability and sometimes lead to cancer.
But when the COVID-19 pandemic caused the temporary shutdown of UB research laboratories last March, Surtees, like many of her colleagues, couldn’t help but consider how her expertise might be applied to the novel coronavirus.
“When the pandemic started, there was a huge surge of interest research-wise into the pandemic and trying to understand how the virus moved around,” said Surtees, PhD, an associate professor of biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB and co-director of UB’s Genome, Environment and Microbiome Community of Excellence.
“I had watched the early genome sequencing coming out of Seattle and California, and I thought we could totally do this here,” she said.
Surtees contacted UB’s Office of the Vice President for Research and Economic Development to ask if anyone at UB was doing genome sequencing of the SARS-COV2 virus isolated from Western New York patients. No one was.
So she contacted Teresa Quattrin, MD, senior associate dean for research integration in the Jacobs School and Special Populations Core director in the Clinical and Translational Science Institute; Gale Burstein, MD, Erie County Commissioner of Health and a Jacobs School faculty member; and Carleen Pope, administrative coordinator of the Erie County Public Health Laboratory. All were enthusiastic about Surtees’ idea.
Where the virus is circulating
“It’s an interesting epidemiological question to get a sense of where the virus is circulating in our community,” Surtees said. “Are there versions that are more pathogenic or infectious? I wanted to see what we could learn about the accumulation of mutations in Western New York patients.”
Surtees explained that rapid genomic sequencing could be used alongside contact tracing to understand transmission of the virus through communities, with the goal of understanding how mutations affect clinical outcomes.
“The goal with this project is to get a sense of the evolution of the virus, and where it came from, to find out its genomic epidemiology, to try and understand the biology of this virus,” said Surtees.
To do that, she worked with researchers in the sequencing core headed by Norma J. Nowak, PhD, executive director of UB’s New York State Center of Excellence in Bioinformatics and Life Sciences. Donald Yergeau, PhD, associate director of genomic technologies in the Genomics and Bioinformatics Core, established a wet lab pipeline to convert the viral (SARS-CoV-2) RNA genomes derived from patients to DNA through reverse-transcription. The DNA version of the entire genome for each sample was amplified in small fragments and subjected to next-generation sequencing.
Jonathan Bard, a senior bioinformatician, then established a bioinformatics pipeline to compare the sequenced Erie County genomes with the reference genome, the original virus that circulated in Wuhan, China, to identify any changes or mutations in the genome. “These genome sequences were uploaded into the nextstrain.org platform to assess phylogeny, a kind of family tree for the viral strains in Erie County,” Surtees explained. “This predicts the path the virus may have taken to get from Wuhan to Buffalo.”
By July, Surtees had received Institutional Review Board approval to study the first batch of 50 deidentified (anonymous) samples isolated from nasal swabs from Western New York patients with COVID-19. They retrieved reliable sequence data from 32 of the samples. Now that that pipeline is in place, Surtees and her team can crank through new samples much more quickly.
“Over time, mutations accumulate; that’s just life,” Surtees said, “It happens in all organisms that replicate their genomes. Studying mutations provides us with an ‘evolutionary path.’ It tells us which genomes are more closely related, the same way we can tell how closely people are related by looking at changes in their DNA sequences. The more mutations that two genomes have in common, the more closely related they are. Genomic sequencing also allows us to see how quickly the virus is mutating.”
How mutations affect infectivity
“The question is to find out how mutations may affect infectivity of the virus, to find out which, if any, mutations are functional and which are just being carried along,” she continued.
In the first batch of samples from patients who were sick with COVID-19 in early April, the majority, approximately two thirds, of virus samples from Western New Yorkers seemed to be of European origin, primarily Italy, France and Spain. The remaining third appears to have come through China and Singapore.
Surtees said the data from the samples will prove more valuable if it is possible to gather more information, such as gender, age and travel history, from the patients from whom the samples were taken. Since the samples were deidentified, that will require permission from Erie County and from each individual patient, as well as approval by UB’s IRB.
Recently, the UB researchers received another 200 samples from the Erie County Public Health Laboratory, which they are running through the pipeline as well.
Surtees has received a small grant from the SUNY Research Foundation to pursue this work, as well as some funding from UB’s Genome, Environment and Microbiome Community of Excellence.
She also has begun collaborating on the COVID-19 research with Amy Jacobs, PhD, a virologist and research associate professor in the Department of Microbiology and Immunology in the Jacobs School, and with Omer Gokcumen, PhD, an evolutionary biologist and associate professor of biological sciences in the College of Arts and Sciences.
They have applied for external funding to the National Institute of Allergy and Infectious Disease of the National Institutes of Health.