Distinguished Speaker Seminar Series in Infectious Diseases
Bryan Hsu and Clayton Caswell
The Center for Emerging, Zoonotic and Arthropod-borne Pathogens (CeZAP) introduces the CeZAP Distinguished Speaker Seminar Series in Infectious Diseases. This university wide seminar series at Virginia Tech invites outstanding scientists nationally to give presentations to CeZAP and broader university community on topics of current interest in the broad area of infectious diseases. Diversity of seminar topics is essential to meeting the purpose of the Distinguished Speaker Seminar Series in Infectious Diseases. Each spring, nominations for nationally distinguished speakers for the seminar series for the following academic year will be solicited from CeZAP affiliated faculty. The seminar coordinators (Drs. Jonathan Auguste and Bryan Hsu) will coordinate the selection of speakers, and the CeZAP faculty nominators will serve as the host for the national speakers. We expect to host at least one nationally distinguished speaker each month, and the remaining speakers will feature our own CeZAP affiliated faculty.
SPRING 2024 SCHEDULE
Seminar Date & Time:
Thursdays at 12:30 - 1:30 pm
In person in LS 1 Conference Room 101
Virtual seminars will be indicated below.
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
Department of Biomedical Sciences and Pathobiology
Virginia-Maryland College of Veterinary Medicine
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)
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.
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
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.