Across a broad array of research applications, virology assays typically monitor changes in the infected host cell over time.  The traditional methods for quantifying these virus-induced cytopathic effects are often labor intensive and only yield endpoint data.  Using gold biosensors that are integrated within microtiter plates, the xCELLigence RTCA family of instruments use impedance to continuously and non-invasively monitor virus-induced changes in host cell number, size, attachment strength, and barrier function.  This composite readout is an exceptionally sensitive means of tracking the entire life cycle of a virus and interrogating virus-host interactions.  In this webinar we will demonstrate how, despite having a simple workflow with minimal hands-on time, xCELLigence RTCA assays yield an abundance of quantitative kinetic information that is being used in both industry and academia for screening and characterizing antiviral drugs.  

The first section of the talk will focus on Agilent’s newest instrument, the xCELLigence RTCA eSight, which couples real-time impedance monitoring with live cell imaging in an information rich assay.  We will subsequently show that once drug candidates have been identified, their cardiac liability can be evaluated from aspects of electrophysiology, contractility and structure using the combined impedance and field potential readouts of the xCELLigence RTCA Cardio ECR instrument in conjunction with human iPSC cardiomyocytes.  

Collectively, this talk will demonstrate a paradigm-shifting workflow that can help populate R&D pipelines with drugs that are well characterized in terms of both efficacy and safety.  

For Research Use Only. Not for use in diagnostic procedures. 
 

Improved treatments are needed for nearly all forms of Mycobacterium tuberculosis (Mtb) infection. Adjunctive host-directed therapies (HDTs) have the potential to shorten tuberculosis (TB) treatment duration, prevent resistance and reduce lung damage by modulating regulatory pathways in dysregulated immune cell populations. In other human diseases such as cancer, diabetes and auto-immunity, HDTs that modulate energy metabolism can improve clinical outcomes. In this study, we looked at TB disease progression and the response to therapy through a metabolic lens. We show that chronic Mtb infection leads to a progressive decline in the metabolic health of T cells that reside in lung lesions, and that metformin HDT can reinvigorate these cells. We also demonstrate that measuring the metabolic health of T cells in patient blood samples can be linked to disease progression as well as to the patient's response to therapy. These findings provide new insights about Mtb pathogenesis that offer unique possibilities for metabolically-targeted immunotherapies to improve current TB treatment outcomes, particularly when standard therapy is no longer an option (i.e., MDR/XDR-TB). 

  Kristin Bircsak, PhD - Principal Scientist, MIMETAS

Kristin Bircsak is a Principal Scientist with MIMETAS, The Organ-on-a-Chip Company in Gaithersburg, Maryland. In 2016, she received her Ph.D. in Toxicology from Rutgers University following which she completed a postdoctoral fellowship at the University of Pennsylvania. In her training, Kristin utilized various model system to characterize the negative impact of drugs and environmental chemicals on reproduction and development. In her role at MIMETAS, Kristin drives the development of innovative 3D in vitro organotypic models and assays. Her research is centered on recapitulating the liver and prostate tumor microenvironment to aid in the accurate prediction of safe and effective candidate compounds.

Kristen N. Peters Olson, PhD -  Imaging Specialist, Field Applications Scientist, BioTek Instruments

Kristen N. Peters Olson, Ph.D. is an Imaging Specialist and Field Applications Scientist for BioTek Instruments in the Greater Boston Area. She received her Ph.D. in Molecular Microbiology and Immunology and Pathobiology from the University of Missouri in 2012. Her dissertation focused on the Yersinia pestis effector protein, YopK, in modulating cell death modality during pneumonic plague. This in vivo infection model focused on the lung immune response to pneumonic plague and was performed in BSL3 conditions at the University of Missouri Laboratory for Infectious Disease Research. In her postdoctoral position at University of Massachusetts Medical School, she studied efferocytosis and its impact on the innate and adaptive immune response in the lung during tuberculosis. To broaden her infectious disease expertise, she accepted a postdoctoral position at the National Emerging Infectious Diseases Laboratories at Boston University, focused on Ebola, Marburg, and Lassa viruses. There, she collaborated with academic colleagues and industry leaders to develop a no-wash diagnostic assay based on SERS technology for the detection of hemorrhagic fever viruses in the field. With the onset of the Zika epidemic, she shifted her focus to Zika virus and developed a novel human placental explant model of infection to understand the cellular tropism, host response, and how the virus causes such severe impact to the developing fetus. This diverse background focusing on host-pathogen interaction in multiple disease models using a variety of assays prepared her for her current position. As an Imaging Specialist for BioTek Instruments, she assists researchers in learning automated imaging technology, developing protocols to best suit their needs, and providing suggestions to improve their research.

Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, In this presentation, we documented the interest of the Real-Time Cell Analysis (RTCA) technology to monitor the cytopathic effects induced by EHV-1 on equine dermal cells, and established the efficacy of this method to evaluate the antiviral effect of aciclovir and ganciclovir . In addition, the RTCA technology has also been found appropriate for the high-throughput screening of small molecules against EHV. Among the 2891 compounds screened, 22 molecules have been found to be effective in vitro against EHV-1. Decitabine, ganciclovir, and valganciclovir, were the most effective compounds identified, and their antiviral potency was further assessed on E. Derm, RK13 and EEK cells and against 3 different field strains of EHV-1 (ORF30 2254A/G/C) using RTCA technology. We also provide evidences of synergistic interactions between valganciclovir and decitabine in our in vitro antiviral assay as determined by impedance measurement and qPCR assays.

For Research Use Only. Not for use in diagnostic procedures.