Hepatitis B Virus
We are using CDMS to study the assembly of hepatitis B virus (HBV). HBV assembly is of particular interest because it is a devastating pathogen and is a target for the development of new assembly-directed antiviral molecules. Learning how to stop the virus from assembling requires knowledge of how it assembles. Unlike conventional MS, CDMS is capable of measuring the mass distribution of complex mixtures in the multi-MDa range and is therefore ideal for measuring the many assembly intermediates for HBV. We have already uncovered late intermediates in the assembly pathway and proposed structures for these species based on their stability and kinetic accessibility.
P22 protein shells can be used in materials applications to transport and protect foreign cargos, such as enzymes. There is typically a broad distribution in the number of cargo molecules encapsulated, and MS of these samples is very difficult. CDMS can easily measure the mass spectrum of mixtures and can be used to determine the distributions of cargo. We have already applied CDMS to P22 capsids to determine the distribution of internal scaffolding proteins.
Adeno Associated Virus
Adeno-associated virus (AAV) is a small DNA virus that is non-pathogenic and exhibits diverse tropism among human and animal tissues. As a result, AAV is a potential candidate as a vector for gene therapy of diseases affecting the eyes, liver, central nervous system, and more. With CDMS, we have obtained some surprising results about the purity and stability of AAV particles that are used in clinical trials for gene therapy.
Zlotnick Lab, Department of Molecular and Cellular Biology, Indiana University – Hepatitus B virus particles
Asokan Lab, School of Medicine, University of North Carolina – Adeno Associated Virus particles
Douglas Lab, Department of Chemistry, Indiana University – Bacteriophage P22 particles
Prevelige Lab, Department of Microbiology, University of Alabama at Birmingham
Teschke Lab, Department of Molecular and Cell Biology, University of Connecticut
Dragnea Lab, Department of Chemistry, Indiana University
Mukhopadhyay Lab, Department of Biology, Indiana University – Sindbis Virus
Stockley Lab, Astbury Centre for Structural Molecular Biology, University of Leeds