Distinguished Speaker Seminar Series in Infectious Diseases

January 18th, 12:30 -1:30 pm, LS1 room 101

“Who’s driving this bus? The Role of MmuPV1 E6 and E7 in pathogenesis" 

10% of all human cancers are caused by viral infections and half of these cancers (5% of all human cancers) are attributed to a single virus, human papillomavirus (HPV). HPV causes a number of malignancies including anogenital cancers, nearly all cervical cancers, a growing number of head and neck cancers, and a subset are associated with non-melanoma skin cancer in people with the genetic disorder epidermodysplasia verruciformis (EV) and long-term immune suppression. Persistent HPV infections to date remains the greatest risk factor for HPV-induced cancers. The current HPV vaccine is prophylactic and does not therapeutically treat current HPV infections. Additionally, the HPV vaccine primarily protects against the cervical and head and neck cancer-causing HPVs and provides no protection against HPVs that cause benign disease or skin cancer. To date, there are no FDA approved antiviral therapies for HPVs and current treatment is surgical intervention or liquid nitrogen treatment. HPV E6 and E7 play critical roles in the HPV’s ability to replicate and promote persistent infection and the mechanisms by which E6 and E7 promote disease are attractive targets for antiviral therapy. To develop antiviral therapies against HPV, strong preclinical mouse models are needed that replicate various stages of the viral lifecycle. However, papillomaviruses are exquisitely species specific and do not typically cause disease in heterologous hosts and has limited the development of mouse models that faithfully replicate early stages of HPV-associated disease. With the discovery of the murine papillomavirus, MmuPV1, the HPV field has a new and powerful tool by which to study and understand all aspects of PV infection. However, our understanding of the molecular mechanisms by which MmuPV1 promotes disease through the activities of the virally encoded oncogenes E6 and E7 and how they relate to known activities of HPV E6 and E7 remains limited. Through our studies, we have found that MmuPV1 E6 and E7 play important roles in pathogenesis and identified a number of cellular processes targeted by these viral proteins. However, we have found unique and exciting roles of these proteins in viral pathogenesis including MmuPV1 E7’s interaction with the tumor suppressors pRB and PTPN14 like HPV E7 and the unique ability of MmuPV1 E6 to promote neoplastic growth. Our current work appears to suggest potentially exciting and novel activities of MmuPV1 E6 and E7, they still subvert the same cellular processes, i.e., different means to the same end.

James Romero-Masters, PhD
Assistant Professor
Department of Biomedical Sciences and Pathobiology
Virginia-Maryland College of Veterinary Medicine
Virginia Tech

January 25th, 12:30 -1:30 pm, LS1 room 101

"Toxic Salmonella: Expanding our understanding of Salmonella’s toxins"

Salmonella is the leading cause of bacterial foodborne illness in the US, causing an estimated 1.4 million cases each year. There are >2,600 serological variants (serovars), of Salmonella enterica with the two model serovars, Typhimurium and Typhi, representing serovars that cause primarily gastrointestinal and invasive disease, respectively. Previous research hypothesized that a single toxin, known as the typhoid toxin, was responsible for the development of typhoid fever, a severe invasive infection resulting from infection with S. Typhi. Our research has demonstrated that the genes encoding this toxin are present in more than 100 non-typhoidal serovars, none of which cause typhoid fever. We have also shown that this toxin is highly conserved and is biologically active in non-typhoidal serovars. This seminar will provide an overview of our current understanding of typhoid toxin and a closely related toxin in the context of this appreciably diverse bacterial pathogen.

Rachel Cheng, Ph.D., Assistant Professor, Department of Food Science & Technology, CALS

Jessica Otis, "Death By Numbers," 12:30-1:30 pm (open to all)
Center for Emerging Zoonotic and Arthropod-borne Pathogens (CeZAP)

Newman Library Goddard Room (101)

Zoom: https://virginiatech.zoom.us/s/89964543462

This talk is based upon the Death by Numbers project funded by the National Science Foundation: "One of the most dreaded diseases in early modern England was plague, which was present in the British Isles from 1348 until 1679. The most well-documented epidemics of the early modern era were in England’s cities, particularly London, which suffered six major epidemics in the century between 1563 and 1665, and lost an estimated 225,000 people to plague. Government officials attempted to quantify the severity of various plague outbreaks and, starting in 1603, published London’s weekly mortality statistics in broadside series known as the Bills of Mortality. The bills grew to include not just plague deaths but also dozens of other causes of death, such as childbirth, measles, syphilis, and suicide, ensuring their continued publication for decades after the final outbreak of plague in England. The weekly bills were also supplemented annually with a general account of the preceding year, published on the Thursday before Christmas. Between 1603 and 1752, almost 8,000 different weekly bills were published, chronicling plague and general mortality through the city of London. Using the DataScribe module for Omeka S, the Death by Numbers project aims to transcribe and publish the information in these bills in a dataset suitable for computational analysis. We then use the Bills of Mortality to investigate how lived experiences of plague outbreaks intersected with an emerging quantitative mentality among the people of early modern England. In particular, we examine how ordinary people aggregated, transformed, and interpreted death counts in order to draw conclusions about changes in the early modern use of and trust in numbers over time. In doing so, we are investigating contemporary perceptions of numbers and historicizes a quantitative method of knowledge generation that has become central to twenty-first-century understandings of the world."

This lecture is part of the Human Dimensions of Infectious Disease Research Colloquium, scheduled for February 1, 2024. More information about the colloquium is available here: https://sites.google.com/vt.edu/etewing/human-dimensions-infectious-disease

Visiting Scholar Dr. Jessica Otis is an Assistant Professor of History and the Director of Public Projects at the Roy Rosenzweig Center for History and New Media. She received her MS in Mathematics and PhD in History from the University of Virginia, and spent four years in the Carnegie Mellon University Libraries as a CLIR-DLF Postdoctoral Fellow and Digital Humanities Specialist. Her research focuses on the cultural history of mathematics, plague, and cryptography in early modern England, and she has particular methodological expertise in network analysis. She has a deep interest in how to make digital humanities projects more accessible and long-term sustainable. In her spare time, she renovates houses and spoils cats.

More information: faculty website / projects / book / death by numbers

Sponsors: College of Liberal Arts and Human Sciences Diversity Grant (link), Center for Excellence in Teaching and Learning (link), and the Diverse Voices and Perspectives Lecture series (link)

Thursday, February 8th: 12:30 - 1:30 pm

VIRTUAL SEMINAR: https://virginiatech.zoom.us/j/89419666443

Host: T.M. Murali

"Optimizing epidemic surveillance with limited screening resources"

Key problems in epidemic surveillance include early  detection of outbreaks and reconstruction of how the disease spread. Testing resources are typically limited, and efficient solutions which optimize testing resources are important. Tests are often pooled which increases their efficiency, but makes them harder to implement. We formalize these problems using the framework of epidemic models on networks, which have been used extensively for COVID, Influenza and Hospital-Acquired Infections (HAIs). We first discuss the problem of early detection and contrast its complexity from other objectives, such as the probability of detection. We present results for early detetion using pooled tests, using stochastic optimization techniques. Next we discuss solutions to the problem of reconstruction of disease outbreaks from available test results using a likelihood mazimization approach, which correspond to variants of the steiner subgraph problem. We present theoretical and simulation results for these problems in the context of the spread of HAIs and multiple variants of a disease such as COVID.

Anil Vullikanti, Professor, Computer Science, University of Virginia Biocomplexity Institute

• Amanda Darling (Cohen Lab)

"Examining Associations Between Inflow and Infiltration and Detection of Viruses and Antibiotic Resistance Genes Across a Rural Sewershed"

Authors: Amanda Darling, Madeline Deck, Benjamin Davis, Gabriel Maldonado Rivera, Sarah Price, Thomas Byrne, Amber Amaral-Torres, Clayton Markham, Peter Vikesland, Leigh-Anne Krometis, Amy Pruden, Alasdair Cohen

• Ying-Xian Goh (Liao Lab)

"Dissemination of antibiotic resistance genes among soil-dwelling Listeria species"

• Morgen VanderGiessen (Kehn-Hall Lab)

 "Comparative Analysis of Equine Encephalitis viruses (EEV), Traumatic Brain Injuries (TBI), and Organophosphorus nerve agents (OPNA) as a path to neuroprotective therapeutics"

February 22, 2024 at 12:30 - 1:30pm in LS1 room 101

Invasive species research now and in the future at Virginia Tech: Opportunities for collaboration

Invasive species, organisms moved by humans to areas outside their historic range, are one of the five grand global threats requiring immediate interdisciplinary action. The Invasive Species Working Group (ISWG) at Virginia Tech was born out of a “Creative Collision” in 2016 within the Global Change Center as an effort to coalesce expertise on campus to work on invasive species-based issues. The ISWG has worked to enhance connections and collaborations of invasive species research, build a coalition of internal and external partners around the state, nationally, and internationally, and provide educational opportunities for students. In 2023 we were awarded one of the two Destination Area 2.0 projects from the Provost’s Office that came with operating funds for five years and a number of faculty lines. I will share more about the ISWG, our vision for invasive species work at VT, and opportunities for collaboration with CeZAP and others on campus.

March 14th: 12:30 pm - 1:30 PM LS1 room 101

Encapsulin nanocompartments in pathogenic bacteria

Encapsulins are icosahedral protein nanocompartments that range in size from 18 to 42 nm and are proposed to be involved in various aspects of prokaryotic metabolism. Encapsulins are prevalent in many important Gram-negative ESKAPEE group pathogens as well as many Gram-positive pathogens including mycobacteria. Encapsulins have been shown to be involved in detoxification, stress resistance, and nutrient storage, processes important for host invasion and proliferation in the hostile environments encountered by pathogens during infection. The eponymous feature of encapsulins is their ability to selectively encapsulate dedicated cargo enzymes during shell self-assembly. In this seminar, I will discuss a recently discovered desulfurase-encoding encapsulin operon in the ESKAPEE pathogen Acinetobacter baumannii. I will present a detailed structural and biochemical characterization of the desulfurase-loaded encapsulin shell and highlight its ability to store large amounts of elemental sulfur. Our characterization lays the foundation for future in vivo studies aimed at elucidating the role of desulfurase encapsulin systems in sulfur and redox metabolism, as well as its impact on pathogenicity. 

Tobias W. Giessen, PhD, Assistant Professor, Department of Biological Chemistry, University of Michigan Medical School

Exploring the role of Culex territans mosquitoes’ in transmitting pathogens to frogs

With amphibians in decline worldwide, it is critical to understand any potential threats to their populations. Culex territans is a mosquito species that feeds primarily on cold blooded animals including frogs and snakes and has been suspected to transmit several pathogens including Ranaviruses and giant anuran trypanosomes to these hosts. Our project aimed at: 1) determining the prevalence of these pathogens along with the fungus Batrachochytrium dendrobatidis and West Nile virus in both mosquitoes and frogs at Mountain Lake Biological Station (Pembroke, VA); 2) exploring the potential role of Cx. territans in transmitting these pathogens. Overall, this project provides important insight into mosquito-host interactions as well as amphibian disease ecology and conservation.

March 28th: 12:30pm - 1:30 pm LS1 room 101

Silencing the Cell: Role of Brucella MucR as an H-NS-like Gene Regulator

Authors: Ian S. Barton ¹ , Zhongqing Ren ³ , Ilaria Baglivo ² , Daniel W. Martin ¹ , Xindan Wang ³ , and R.Martin Roop II ¹

Institutions: ¹ Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC; ² Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy; ³ Department of Biology, Indiana University, Bloomington, IN

Proper coordination of host-associated behaviors is critical for bacteria that are pathogens or symbionts. The global transcriptional silencer H-NS is a nucleoid-associated protein (NAP) that is important for coordination of virulence in many bacteria including Escherichia coli, Shigella, Salmonella, and Vibrio. In these bacteria, H-NS-mediated gene silencing is overcome through direct antagonization via transcriptional counter-silencers that bind to gene promoter regions, displace H-NS, and permit transcriptional activation of key virulence genes at the proper time. Brucella spp. and related members of α-proteobacteria lack functional H-NS homologs, so it is unclear whether other proteins are involved in performing analogous functions during host-association and pathogenesis. We have recently identified the Zn finger protein MucR as a novel H-NS-like protein that is critical for virulence in Brucella spp. We combined ChIP-seq and genetic and biochemical approaches to demonstrate that MucR works in concert with antagonistic counter-silencers to ensure the proper temporal regulation of genes encoding important virulence determinants. Additionally, we have demonstrated that Brucella MucR, like H-NS, plays an important role in maintaining nucleoid structure. Interestingly, hns from E. coli can functionally complement mucR mutants in Brucella spp. despite limited amino acid similarity and differences in observed oligomeric states. Current work aims at understanding the molecular mechanisms underlying counter-silencing and the importance of temporal regulation of discrete targets by MucR during host-association and pathogenesis. In total, our work solidifies the role of MucR as a novel type of H-NS-like protein and suggests that MucR’s gene-silencing properties play a key role in virulence in Brucella.

“Vector-Borne Emerging Infectious Diseases of Concern with the Potential to Affect U.S. Agriculture”

The National Bio and Agro-Defense Facility, or NBAF, located in Manhattan, KS is a new state-of-the-art high containment facility operated by the U.S. Department of Agriculture that will help protect the nation’s agriculture, farmers and citizens against the threat and potential impact of serious animal diseases. One of the threats investigated at NBAF will be Vector-borne emerging pathogens which can cause significant disease, economic loss and pose a threat to the U.S. livestock industry. Additionally, these vector-borne viruses have the potential to infect animals and spread to humans (zoonotic transmission) which places this mission at NBAF as part of the One Health approach where vector-borne disease threats to livestock will be investigated while simultaneously having an effect on the health of farmers, veterinarians, meat producers and consumers.

Chad Mire, PhD
Research Leader
Foreign Arthropod-Borne Animal Diseases Research Unit
National Bio and Agro-Defense Facility
USDA Agricultural Research Service (ARS)

"Eating for two (trillion): Unraveling gut microbial responses to dietary nutrients"

Industrialized food production has reshaped the human diet by simultaneously reducing dietary fibers while increasing simple sugars. We investigate how these dietary changes impact prominent members of the human gut microbiome.

Guy E. Townsend, Ph.D.
Assistant Professor
Penn State College of Medicine
Department of Biochemistry and Molecular Biology

"Bacteriophage-Bacterium Encounter, Lysis, and Antagonistic Coevolution"

Bacteriophages are viruses of bacteria. Their basic life cycle consists of bacterial acquisition, infection, and release. Meanwhile, bacteria do their best to evade these steps, resulting in evolutionary arms races also described as antagonistic coevolution. Here I combine theoretical and experimental approaches to explore factors underlying virion encounter rates with bacteria, variation in phage lysis timing, and the potential especially for phages and bacteria to go through multiple rounds of (i) mutation to phage resistance and (ii) phages overcoming that resistance, all over relatively short spans of time. Emphasis is on a diversity of viruses infecting Escherichia coli.

Stephen Abedon, PhD
Professor of Microbiology
The Ohio State University

Reengineering the gut bile acid landscape to to restrict C. difficile 

Antibiotics can have significant and long-lasting effects on the intestinal tract microbiota, reducing colonization resistance against pathogens including Clostridioides difficile. We have shown that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Our work indicates that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. Many of the metabolites that influence C. difficile physiology are products of gut microbial metabolism including bile acids, carbohydrates and amino acids. To restore colonization resistance against C. difficile after antibiotics a targeted approach restoring both the structure and the function of the intestinal tract is needed.

Dr. Theriot’s current research focuses on how gut microbial derived secondary bile acids inhibit the C. difficile life cycle using in vitro and in vivo models. She is also working on manipulating the gut microbiota to rationally alter the composition of the bile acid pool in the gut, which has the potential to improve preventative and therapeutic approaches against many human diseases. The goal of her work is to design targeted bacterial approaches to prevent and treat gastrointestinal diseases – improving clinical outcomes. Dr. Theriot is a member of the Comparative Medicine Institute at NCSU and the Center for Gastrointestinal Biology and Disease at UNC. She has received multiple pilot and NIH research awards for her research on C. difficile including a Mentored Research Scientist Development Award in Metabolomics (K01), and multiple Maximizing Investigators' Research Award (MIRA) (R35) from the NIGMS.