Seminar: Dr. Shiladitya DasSarma, UMB-IMET
Title: "Molecular genetic analysis and biomedical applications of haloarchaeal virus-like nanoparticles"
Speaker: Dr. Shiladitya DasSarma, UMB-IMET
Abstract: Halophilic Archaea such as Halobacterium sp. NRC-1 produce large quantities of hollow, buoyant, virus- like nanoparticles called gas vesicles (or GVNPs) (1). GVNPs are extremely stable, proteinaceous, non- toxic, self-adjuvanting, and easily purified after hypotonic lysis of the salt-loving microorganisms. A tightly organized gene cluster on a large plasmid, gvpMLKIJHGFFEDACNO, was implicated in their biogenesis through extensive molecular genetic analysis. Two proteins, one amyloid-like (GvpA) and the other soluble (GvpC), were shown to constitute major structural components of the nanoparticle, and at least five additional proteins serve as minor structural or assembly components. Foreign sequences inserted at the C-terminal region of GvpC resulted in their display on the nanoparticle surface (2,3). An improved genetic system has recently been developed to allow for a more facile display of foreign sequences, including antigenic and therapeutic peptides and proteins (4-7). Displayed antigenic proteins include envelope proteins, enzymes, and extracellular secreted proteins followed by testing of protection using disease models in several cases. The source of foreign proteins displayed on the surface of GVNPs thus far include antigens from the simian immunodeficiency virus (SIV) (3), a facultative intracellular pathogen, Salmonella enterica (5), and the parasitic protozoan Plasmodium spp. (6), as well an innate immune system protein from mice (7). Most recently, we also established that GVNPs may be delivered by microneedle administration (8), further expanding the versatility of the system for biomedical applications.
References: 1. Vaccines 3:686-702, 2015; 2. Journal of Biotechnology 88:119-128; 3. Journal of Biotechnology 114:225-237, 2004; 4. BMC Biotechnology 13:112, 2013; 5. Vaccine 32:4543-4549, 2014; 6. Malaria Journal 14:406, 2015; 7. Scientific Reports 6:33679, 2016; 8. Molecular Pharmaceutics 14:953- 958, 2017.