Research

By Sarah Rubinstein | Bond LSC

Growing up in ’70s and ’80s Britain, 10-year-old Anthony Griffiths’ brain had the dangers of rabies seared into it during European vacations. At the time, rabies hadn’t made its way to Britain but was present throughout the continent, and the public service announcement posters were a fearful reminder to remain vigilant. While messages warning against smuggling unquarantined pets into the country scared most children with statements like “rabies means death” and “rabies is a killer,” Griffiths was curious. He went to the library instead, checked out a book — “Rabies: The Facts” and his interest in virology was born.

“I’m the luckiest person in the world, who’s done exactly what I have always, always wanted to do,” he said. 

The British native arrived at Mizzou in July to become the newest director of Mizzou’s Laboratory for Infectious Disease Research (LIDR) and a principal investigator at Bond Life Sciences Center.

Griffiths has spent his career researching viruses in high and maximum biocontainment labs, working to understand how they cause disease and how the information he finds can be used to develop vaccines and therapeutics for those viruses. 

“Viruses are so simple, they are not even alive, but they are so devastating,” he said. “Understanding how something so simple can have such an impact is fascinating.”

He received his Ph.D. in virology at the University of Cambridge and studied herpes viruses at Harvard Medical School, focusing on the cellular biology of herpes and using antiviral agents to probe how the virus causes disease. Then he began his own infectious disease laboratory at Texas Biomedical Research Institute where his team mostly analyzed viruses at biosafety levels three and four (BSL -3 and BSL-4). Biosafety level four is the highest classification of biological safety for working with the highest risk viruses. In Texas, he looked at a pathogenic zoonotic virus that causes herpes B virus. He also worked on more “famous” viruses like Ebola. 

After that, Griffiths was recruited to the National Emerging Infectious Diseases Laboratories at Boston University that had a BSL -4 facility. He worked in Boston through the beginning of the COVID-19 pandemic, where he looked at ways to recycle personal protective equipment used in labs and began looking at passive ways to inactivate the virus on surfaces then tested drugs and vaccines as they started to be developed.

Coming to Mizzou, Griffiths is fascinated with Bond LSC’s ambitious nature that pushes for collaboration with other parts of campus including the School of Medicine and the College of Veterinary Medicine.

“Every university would tell you it values collaboration, but I think Mizzou really strives to have everyone work with each other,” he said.

Griffiths looks forward to the possibility of working with students and hopes being located on the main campus will help facilitate interactions with them. Unlike the work he did in Boston, Griffiths is interested in putting on his biologist hat to investigate animal modeling in his academic lab at Bond LSC where he can recruit students to study the intersections between humans and animals. 

While half of his time will be at Bond LSC, directing LIDR also is a substantial undertaking.

LIDR, one of only 13 federally supported Regional Biocontainment Laboratories in the U.S., has research laboratories for studying basic biology of infectious diseases in high biocontainment, such as plague and avian influenza virus. But LIDR also serves as a regional resource of the federal government in the event of infectious disease outbreaks. 

As LIDR’s director, Griffiths will focus on outreach to campus and spreading awareness of it as a fundamental resource to the area. He also will represent the lab in national and international conferences. He is most looking forward to bringing in new viruses and techniques to study. As a federal and regional resource, LIDR will study whatever pathogens are most important and relevant for public and animal health to the U.S. at any point in time. Therefore, he and his team will be ready to respond to whatever is needed. He likens this to transitioning a lot of his former work to studying SARS-CoV-2, the virus that causes COVID-19. 

From a scientific standpoint, he is most excited to study hantaviruses because he’s never had the chance to study them before, but notes that this could be pushed down on the priority list as new things arise.

“Reacting to what’s happening is part of the job, that’s why you recruit lab members with a variety of expertise,” he said. 

Coming onto campus with two big roles, Griffiths wants his future colleagues and students to understand why he chose Mizzou. He believes that the school’s friendly nature, field of opportunities and push for collaboration makes it the ideal place for him.

By Sarah Rubinstein | Bond LSC

As animals face increasing pressure from habitat loss and changing climate in the wild, zoos worldwide strive to reinforce diversity for at-risk populations among their inhabitants.

So, when Rachel Carroll took charge of creating a genetic blueprint for the fishing cat — a feline native to Southeast Asia — she had one eye toward helping the often-overlooked “grumpy, overgrown house cat.”

“We’re hoping that we can really showcase the power that genetics can play in understanding not just the organism but diseases that could be occurring within them as well,” said Carroll, research specialist and lab manager in the Wes Warren lab at Bond Life Sciences Center.

Fishing cats were the heart of Carroll’s masters project she started in 2020. This species stands out from other cats with its affinity for water, unique swan diving technique used to catch food and moody personality. The International Union for Conservation of Nature lists these cats’ conservation status as “vulnerable,” and zoos have found that older fishing cats have a higher prevalence of bladder cancer.

Published in Nature’s Scientific Reports, Carroll’s effort to create a reference genome partly aimed to find gene mutations in fishing cats potentially linked to bladder cancer. Using genes from 11 cats at zoos across the country — some with bladder cancer and some cancer free — she looked at the cat equivalent of 152 genes known to increase cancer risk in humans, with 10 of those specifically linked to bladder cancer. That allowed her to identify a specific cat gene mutation that could lead to higher rates of bladder cancer. Since only 25 fishing cats are captive in U.S. zoos, many share a genetic pedigree that may result in higher rates of inherited disease. 

“The work includes taking genetic sequences from affected cats — cats that are cancer free — and comparing those sequences to a reference genome for that species to see the differences and similarities within the sequences of these cats,” she said. 

Creating the genome required mastering bioinformatics, a challenge Carroll welcomed. After learning to code, she operated Mizzou’s supercomputer to synthesize the complete genome. 

She used a variety of bioinformatic programs to analyze if the fishing cat genome contains similar gene sequences to the known cancer risk genes in humans, and then she identified these mutations within the 11-cat dataset. Next, she used another program to determine if these mutations have a harmful effect on the organism. 

Carroll found the gene BRCA2 to be more prevalent in cats with cancer compared to cats without, however, since her sample size was small, she cannot definitively say that this gene causes cat bladder cancer. 

Carroll noted this study is just a jumping off point for exploring the genome of this species and, ultimately, promoting conservation. By understanding the genetic basis of diseases like bladder cancer, conservationists can develop better strategies to protect fishing cats and other endangered species. Zoological institutions will also have information to guide better management strategies to help decrease the chances of disease occurrence in a smaller population.

Carroll noted other major factors impact animal populations that are important to consider. Heavy deforestation, aquaculture development and farming development all lead to habitat loss, which is a danger to these cats as well. 

“Habitat loss is really the biggest driver and risk factor for all species on Earth right now,” she said. “And, unfortunately, until we can get a really good hold on that, it’s really hard to find ways to promote conservation efforts since that’s happening so rapidly.”

For now, she’s happy to increase interest in these lesser known apex predators to show fishing cats are just as essential to their natural ecosystems as other big cats. 

“That’s something I really pride myself on, being able to communicate science better to people so that we can actually have action and excitement about trying to make the world and the environment a better place for us and everything else that’s living in it,” she said. 

By Sarah Rubinstein | Bond LSC

When Marc Johnson set out to find the source behind the mysterious combinations of coronavirus mutations he found in wastewater, he had no idea this work could one day be his legacy. 

“If there’s anything in my career that’s ever cited in 100 years, it will be this study,” said Johnson, a principal investigator at Bond Life Sciences Center. 

The research details how scientists narrowed a search for a cryptic lineage of SARS-CoV-2, the virus that causes COVID-19, from sewer shed sampling in Wisconsin. The work was published in The Lancet Microbe in April, but his first study on cryptic lineages was referenced by Stephen Colbert and Freakonomics Radio featured his new work on their podcast.

Finding the source of a mysterious viral strain in wastewater was like “finding a needle in a haystack,” Johnson said.

Cryptic lineages are sequences of strange viral combinations of mutations contained in one place that don’t spread like prevalent variants of the SARS-CoV-2 virus, like Delta or Omicron. Cryptic lineages have never been identified in a source beforehand, but wastewater testing allows scientists to pick up on these mutants that aren’t otherwise readily detected through more traditional testing. 

When Johnson identified these highly divergent cryptic lineages in wastewater sent by the Wisconsin Department of Health Services, he assumed it had come from an animal reservoir or nursing home. Except, he was wrong. By going manhole to manhole, they tested wastewater to track down the source to a small, 30-person company in Wisconsin. Johnson said it likely came from one person.

“I could not believe how much COVID-19 there was in that sample,” he told Freakonomics Radio. “It was 1,000 times higher than anything I’d ever seen.”

This level of virus comes from viral shedding – when an infected person’s cells make new copies of the virus that are then excreted from the body. After narrowing the source to a specific company and even the exact toilet, Johnson offered free employee testing to get to the bottom of it. Since only two-thirds of employees got tested, he could not find the culprit. 

However, he did figure out how a single person could shed enough SARS-CoV-2 to be detected in wastewater. It likely comes down to a long-term infection in a person with a compromised immune system. 

“It probably means there was someone in that sewer shed that was infected with a variant for two years, and then they suddenly started shedding enough that we could detect it,” he said. “So, the question is, how many more of these people like this are out there?”

Johnson’s next task is to investigate other patients with persistent GI infections since they had COVID-19, or patients who believe they have long COVID-19. To do that, he’s spent the past nine months asking for people from all over to donate their stool samples if they match these characteristics. He infers that many long COVID-19 patients have had ongoing COVID-19 for years without knowing it, some contracting it as early as 2020.

Once he identifies similar people, he wants to learn what symptoms they have in common. Since he hasn’t found the exact person who has caused the cryptic lineage from The Lancet Microbe study, he doesn’t know what the long-term effects would be for persistent infections, but Johnson hypothesized it could involve a GI tract infection that doctors can’t detect from a typical nasal swab test.

Getting participants to donate stool samples is a much harder sell when trying to convince potential subjects why donating samples is important. Since testing isn’t mandatory, he offers it for free, hoping it will encourage participation and ultimately help people, he said.

“The biggest challenge has just been the conflict between public health and individual privacy,” he said.

While the big takeaway is that some people have long-term COVID-19 infections without knowing it, Johnson cautions care must be taken in linking a specific person to an infection because it could open them up to community or workplace scrutiny or retaliation. He estimates that one in every 1,000 infections is persistent, but this level of viral resistance is still potentially harmful, as these individuals could be “a potential source of lineages that could make our hard-fought immunity less useful.”

Johnson and his team were never in it for the recognition, but all the attention has brought awareness to his efforts, and he still hopes to identify and help these long COVID-19 patients.

“I still have some questions; I’m going to keep chipping away at it until we either figure it out or they just go away, but I don’t think they’re going to go away,” he said.

By Sarah Rubinstein | Bond LSC

For a researcher passionate about making crops more resilient against diseases, working in a rapidly growing, influential country was a huge opportunity. 

Bing Yang, a Bond Life Sciences Center principal investigator, put his knowledge into practice earlier this year in India thanks to a recent Fulbright Specialist Program award. 

“It was a very rich experience for me to go there and have that firsthand experience in a foreign country,” Yang said. 

Yang ran a two-week project at Punjab Agricultural University in India, leading workshops and giving lectures on genome editing in plants. As a scientist who works with technologies that improves a crop’s disease resistance and makes plants as efficient as possible, he was especially interested in sharing his findings in India to bridge the information gap to help ramp up productivity in India. 

“India is the most populous nation in the world and agriculture is a big part of their economy, so they’re very interested in technologies to make their plants more productive,” he said. 

Yang learned of the Fulbright opportunity when a visiting scholar from Punjab Agricultural University came to work in his lab and encouraged him to apply. The Fulbright Specialist Program links Indian and American universities and institutions to draw on the expertise of U.S. scholars. Specialists enhance their understanding of the cultural and educational contexts of the host country while educating in their areas of expertise, according to the United States – India Educational Foundation website.

Once he arrived, Yang adapted his teaching style to a different set of students. While his students at Mizzou were well-versed in this technology, he had to approach this workshop from the ground up. He also faced the struggle of educating the students within such a short period of time. 

“The first step I took was giving them the big picture about the technology,” he said, “and then they can simulate or teach other pupils in order to expand the technology.”

Throughout his workshop, he connected with the students and their excitement to learn. His students even sent him back news articles documenting their collaboration.

“It was a wonderful experience, they loved to hear lectures especially from people from other countries.” 

The experience left Yang wanting to extend the collaboration further. He is interested in going back to hold another workshop and hopes to create an exchange program between students and faculty from the universities. 

“They’re a diverse body of students and participants who learned from this hands-on experience in such a short time,” he said. 

Find more about this Fulbright grant and other cross-cultural educational opportunities at www.usief.org.in.