Protection from dengue pathogenesis by targeting dengue virus nonstructural protein 1
Eva Harris, Professor
Public Health; Div of Infectious Diseases and Vaccinology
Closed. This professor is continuing with Fall 2024 apprentices on this project; no new apprentices needed for Spring 2025.
With 3.6 billion people living at risk of infection, and approximately 400 million infections and 96 million cases per year, dengue is the most prevalent mosquito-borne viral illness. The disease spectrum includes dengue fever, characterized by debilitating symptoms such as high fever and myalgia; and dengue hemorrhagic fever/dengue shock syndrome, with life-threatening manifestations stemming from vascular leakage that leads to shock. Dengue virus (DENV) nonstructural protein 1 (NS1) circulates in patients’ blood during acute infection, and high levels of NS1 are associated with severe disease. Our laboratory has demonstrated that NS1 is a direct trigger of DENV-associated endothelial permeability and vascular leak. We also showed that the pathogenic effects of NS1 can be blocked by NS1-immune polyclonal mouse serum or by monoclonal antibodies (mAbs) to NS1, and that immunization of mice with NS1 protects against lethal DENV challenge. We are also interested in innate immune pathways triggered by NS1 activity. Currently, our goal is to interrogate the role of NS1 in DENV pathogenesis and/or protection using a combination of immunological ex vivo and murine in vivo assays in order to uncover new therapeutic strategies for treating dengue-associated vascular leak.
Role: The goal of this project is to investigate DENV pathogenesis by targeting host pathways activated by NS1. Training will be focused on development and implementation of various in vivo and ex vivo experiments done in mice. It is also expected that the URAP apprentice will learn how maintain animal breeding colonies and to handle, wean and genotype mice. Skills learned will include but are not limited to: murine husbandry, murine infection models, murine vascular leak models, blood and tissue collection, enzyme-linked immunosorbent assays (ELISA), protein production, basic cell culture techniques and basic molecular biology techniques. The URAP student is also expected to attend weekly research meetings and maintain detailed records of the work performed. The URAP apprentice will work with and under the supervision of Pedro Carneiro, a graduate student in Dr. Eva Harris’ laboratory.
Qualifications: Experience with animal handling is highly preferred, and a strong interest in immunology, pathogenesis, and infectious disease is desirable. Additional requirements include organizational skills, attention to detail and high motivation and enthusiasm. Working knowledge of Excel is a plus.
Day-to-day supervisor for this project: Pedro Carneiro, Graduate Student
Hours: 12 or more hours
Related website: https://www.harrisresearchprogram.org
Biological & Health Sciences