INTRODUCTION: The Broadbent Lab aims to advance our understanding of the molecular basis underpinning the replication and pathogenesis of viruses that infect animals, to better prevent and control diseases of animals and people. Current projects are focused on RNA viruses that cause diseases of significant economic importance to the poultry industry, including infectious bursal disease virus (IBDV) and avian reovirus (ARV). These viruses can cause extensive morbidity and mortality, as well as immunosuppression, which decreases the efficacy of vaccination programs and increases the susceptibility to secondary infections, some of which are zoonotic.
The lab uses these viruses as tools in order to:
- Improve the control of animal viruses: Improve the efficacy of current vaccines, improve the design of future vaccines, identify gene targets for engineering more resistant animals
- Model immunosuppression: Determine how immunosuppression in livestock impacts upon the pathogenesis, evolution & transmission of potentially zoonotic infectious diseases, define immunosuppression at mucosal surfaces, characterize the recovery from immunosuppression
- Determine viral replication mechanisms: Define the nature of virus factories, characterize the host-cell antiviral response, determine the molecular mechanisms underpinning reassortment
- Control other diseases in animals and humans: Determine the utility of viruses as vaccine vectors and in oncolytic viral therapy
We use a blend of in vitro cell culture, primary tissues and cells, and in vivo studies, and employ molecular biology, immunological, and bio- imaging techniques in the lab.
DESCRIPTION: It is possible to design and synthesize viruses in the laboratory, through a process known as “reverse genetics”. This technique allows us to custom-build viruses, opening the potential to generate new rationally designed vaccine candidates against viral diseases of animals and people. Reoviruses infect a diverse range of species, including humans. Moreover, some reoviruses can infect and destroy cancer cells, and show promise in what is known as “oncolytic virotherapy”. In this project, we aim to engineer a reverse genetics version of an avian reovirus that is of significant economic burden to the US. This will allow us to create a novel vaccine candidate and investigate the potential of using the virus in oncolytic virotherapy. The proposed project involves cloning the genes that make up the virus, engineering the reverse genetics virus in cell culture, sequencing the virus, and characterizing the virus replication kinetics in host cells.
IDEAL CANDIDATES: The project is well-suited for a motivated and talented student studying in the School of Medicine or the School of Pharmacy with interests in molecular virology. The successful candidate will acquire experience and skills including gene cloning, cell-culture, transfections, infections, immunofluorescence microscopy, PCR, reverse-transcription quantitative PCR (RTqPCR), and virological techniques such as plaque assays, that can be applicable to many different animal and human viruses in the future.
PROJECT LEAD/PRINCIPAL INVESTIGATOR: Andrew Broadbent, PhD, Assistant Professor, Department of Animal and Avian Sciences, University of Maryland, College Park