Charlie Rice gives the history of learning to grow hepatitis C virus in culture, from pitfalls to hurdles and successes along the 20-year journey. He also talks about yellow fever virus, its vaccine, and the importance of curiosity-driven research

082: The struggle to study hepatitis C virus with Charlie Rice

Who is microbiology? Meet the Microbiologist (MTM) introduces you to the people who discover, innovate and advance the field of microbiology. 

Go behind-the-scenes of the microbial sciences with experts in virology, bacteriology, mycology, parasitology and more! Share in their passion for microbes and hear about research successes and even a few setbacks in their field. 

MTM covers everything from genomics, antibiotic resistance, synthetic biology, emerging infectious diseases, microbial ecology, public health, social equity, host-microbe biology, drug discovery, artificial intelligence, the microbiome and more! 

From graduate students to working clinicians and emeritus professors, host, Ashley Hagen, Scientific and Digital Editor at the American Society for Microbiology, highlights professionals in all stages of their careers, gleaning wisdom, career advice and even a bit of mentorship along the way.

Science

Life Sciences

Rodney Rohde, Ph.D., Regents’ Professor and Chair of the Medical Laboratory Science Program at Texas State University discusses the many variants, mammalian hosts and diverse neurological symptoms of rabies virus.  Take the MTM listener survey! Ashley’s Biggest Takeaways:  Prior to his academic career, Rohde spent a decade as a public health microbiologist and molecular epidemiologist with the Texas Department of State Health Services Bureau of Laboratories and Zoonosis Control Division, and over 30 years researching rabies virus. While at the Department of Health Lab, Rohde worked on virus isolation using what he described as “old school” cell culture techniques, including immunoassays and hemagglutinin inhibition assays. He also identified different variants of rabies virus, using molecular biology techniques. Rohde spent time in the field shepherding oral vaccination programs that, according to passive surveillance methods have completely eliminated canine rabies in Texas. In the last 30-40 years, most rabies deaths in the U.S. have been caused by bats. Approximately 98% of the time rabies is transmitted through the saliva via a bite from a rabid animal. Post-exposure vaccination must take place before symptoms develop in order to be protective.  Links for This Episode:  Molecular epidemiology of rabies epizootics in Texas. Bat Rabies, Texas, 1996–2000. The Conversation: Rabies is an ancient, unpredictable and potentially fatal disease. Rohde and Charles Rupprecht, 2 rabies researchers, explain how to protect yourself.  The One Health of Rabies: It’s Not Just for Animals. MTM listener survey! 

Rabies: The Diabolical Virus With Many Symptoms and Hosts With Rodney Rohde

ASM's Young Ambassador, Aureliana Chambal, discusses the high incidence of tuberculosis in Mozambique and how improved surveillance can help block disease transmission in low resource settings.  Ashley's Biggest Takeaways:  Mozambique is severely impacted by the TB epidemic, with one of the highest incidences in Africa (368 cases/ 100,000 people in the population). Human-adapted members of the Mycobacterium tuberculosis complex (MTBC) belong to 7 different phylogenetic lineages. These 7 lineages may vary in geographic distribution, and have varying impacts on infection and disease outcome. For decades, 2 reference strains have been used for TB lab research, H37Rv, which Chambal mentions, and Erdman. Both of these belong to TB Lineage 4. According to Chambal, the reference strains that we use for whole genome sequencing (worldwide) may be missing genes that are related the virulence (and/or resistance) of strains that are circulating in a given population and detected in clinical settings. Chambal is endeavoring to employ a new strain to control these analyses and better understand transmission dynamics in the community setting.  Featured Quotes:  The Schlumberger Foundation Faculty for the Future Fellowship is one of my proudest accomplishments for the 2023. I applied for this fellowship last year to pursue my Ph.D. It is a program that supports women coming from emerging and developing economies to pursue advanced research qualifications in science, technology, engineering and mathematics. I applied because I was looking to get more skills in microbiology, specifically tuberculosis, to pursue my Ph.D. at Nottingham Trent University. Pathway to Microbiology Research My trajectory is different because I have a bachelor’s in veterinary medicine. And during my undergrad, I always had more interest in the lab practice modules or disciplines. For the end of the [bachelor’s] project, I was looking to understand the anthelmintic effectiveness against the gastrointestinal parasites in goats. After I finished this project, I was looking to continue a related project, but unfortunately, I couldn't get work related to that..  In 2016, I applied for the National Institutes of Health of Mozambique, which is one of the biggest research institutions in my home country. That's when I was selected to work at the north region of Mozambique, specifically at the Nampula Tuberculosis Reference Laboratory. And then I moved to the public health laboratory as well, where I had the opportunity to work in the microbiology section. So, to be honest, my passion for microbiology started when I had the first contact with the TB lab, and then I couldn't separate myself from this area, tuberculosis.  In 2016, I had the opportunity to receive a mentorship. Our lab, the TB lab of Nampula, received mentorship from the American Society for Microbiology. And we worked with Dr. Shirematee Baboolal; she was the mentor of our lab. The main idea of the program was to get the lab accredited and to build technical capacity in the lab. And to be honest, at the time, I didn't have much experience in lab techniques to detect or diagnosis tuberculosis.  And I said to Dr. Shirematee, “I don't have much experience in this area, so, I don't know if I will be able to help you to accomplish these goals.” And she said, “If you want to learn, I can teach you, and you can be one of the best in this area.”  And then we started training with her. It was very interesting. The passion she passed to us about microbiology—and tuberculosis, in particular—was one of the triggers for my passion in this area. So, to be honest, Dr. Shirematee Baboolal was one of the persons that triggered my interest from tuberculosis. So, I have to say thank you to her! Tuberculosis Genomic Diversity and Transmission Dynamics Mozambique is one of the higher burden countries of tuberculosis. So, our population is about 33 million people. And the case rate is high, it is approximately 360 per 100,000 people in the population, which is equivalent to over 110,000, which is equivalent 211,000 cases in the population. So, while I was working for the TB lab, I always had the desire to understand more about the transmission of the disease in the community.  And I felt like I didn't have enough skills to do that; I didn't the tools to do that. And I said, “Okay, let me try to look to improve the skills.” That's why for my master's degree I tried to understand the genomic diversity of M. tuberculosis and see how we can see the gene content diversity within the lineage for which is the most spread lineage worldwide, and is predominant in Mozambique. Afterwards, I tried to expand to the other lineages.  When I finished my master's degree, I felt that it was still missing something. I had the information about [TB] diversity, but I didn't get the point about transmission itself. That's why, when I went back and applied for my Ph.D., I structured my current project to specifically look at transmission and transmission clusters in the community.  I'm trying to see how we can expand the gold standard of whole genome sequencing to try to make it applicable for all settings, including the low resources settings where most TB cases happen.  So, M. tuberculosis itself doesn't have a lot of diversity between strains and within strains, because [strains] are very monomorphic. But you can find some genes that are different, specifically from the reference strain that we use, which is H37Rv. In the reference strain for M. tuberculosis, we saw is that many genes are missing—genes that are related to virulence. So, this information can be tricky, because it's the reference that we use worldwide to analyze our samples that come from whole genome sequencing. If we have genes missing, we are not [seeing] the complete information about the virulence of the bacterial strain that is circulating. So, my analysis was trying to understand how we can employ a new strain (that has at least most of the genes that are present in the other screens of the lineage) to control our analysis.  Whole genome sequencing requires a lot of computational resources. So, the main idea is to try to extend that pipeline to make applicable to use in all settings.  In Mozambique, we have whole genome sequencing equipment at the central level of the country, and the demand is high. But there is a queue for processing the samples. So, if we have a pipeline that [makes it so] anyone is able to analyze the data, we can have the results quick, and we can have more information for the public health sector.  And with transmission studies, you can have a clearer idea of where the recent infection happened. We can see how many cases we have and when the transmission started. And then we can [try to] track and block the transmission. Involvement with ASM Young Ambassador Program So, I had the opportunity to hear about ASM’s Young Ambassador Program while I was working at the TB lab, in 2018. I spoke to Dr. Shirematee Baboolal and Dr. Maritza Urrego. And they told me about this position. Then, once I finished my masters [program], I applied for that position. I saw the requirements, and I felt like it was the right position for what I wanted to do for my community—to support the youth community and engage with my community back in Mozambique. I applied in 2020, and I got the position.  And I have to say, it is one of the best things I have done so far. Because since the implementation of this program in Mozambique, I have interacted with students in schools and universities. We have developed a lot of workshops. I feel like I can contribute scientifically to improve their lives, to improve their academic lives. And recently, we launched a program called Microbiology Kids Club. We go to schools, in church, and we teach children about science, specifically microbiology. We use cartoons and paint microbes to explain the importance of the microbes for the community for our daily activities. And it's very interesting how they are engaged. I can feel that it's a way to develop the taste for science in the children. So, I'm very happy with this accomplishment. In this role of young ambassador, I feel like I can contribute to my community back home.  I have so many ideas, so many dreams. I don't even know where to start! Because I have the ambitions to support my country back home. After I finish my Ph.D., I would like to create a robust technique that will help us to properly understand the [TB] transmission studies. So hopefully, with my Ph.D., I will be able to do that, or at least contribute something to support not only my country, but all low resources settings.  And I would also like to be like to support some public health policies that can help us. Because we don't have like a strong component that involves the lab, the public health sector—I feel like everything is separated. We need to combine everything if we want to fight against tuberculosis. So, my desire is also to create a link between all these specific sites so we can make our fight against TB stronger. I want to continue [to drive] awareness about the support we need in low resource settings to control the fight against tuberculosis. Links for the Episode:  ASM Ambassador Program. ASM Global Public Health Program. 

Increasing Laboratory Capacity for TB Diagnosis With Aureliana Chambal

 The scientific process has the power to deliver a better world and may be the most monumental human achievement. But when it is unethically performed or miscommunicated, it can cause confusion and division. Drs. Fang and Casadevall discuss what is good science, what is bad science and how to make it better. Get the book! Thinking about Science: Good Science, Bad Science, and How to Make It Better

Good Science, Bad Science and How to Make it Better with Ferric Fang and Arturo Casadevall

Dr. James Morton discusses how the gut microbiome modulates brain development and function with specific emphasis on how the gut-brain axis points to functional architecture of autism. Watch James' talk from ASM Microbe 2023: Using AI to Glean Insights From Microbiome Data https://youtu.be/hUQls359Spo

Using AI to Understand How the Gut-Brain Axis Points to Autism With James Morton

Dr. Michael ginger, Dean of the School of Applied Sciences in the Department of Biological and geographical Science at the University of Huddersfield, in West Yorkshire, England discusses the atypical metabolism and evolutionary cell biology of parasitic and free-living protists, including Leishmania, Naegleria and  even euglinids.

082: The struggle to study hepatitis C virus with Charlie Rice

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