Open Sesame: Cell Entry and Vaccinia Virus
Lecture focuses on a single virus, the Vaccinia virus, as a model for cell binding, signaling and endocytosis. Fluorescently labeled Vaccinia viruses bind to and surf along host cell filopodia. Helenius lab members noticed that when Vaccinia, unlike other viruses, reached the surface of the cell body it caused the plasma membrane to form blebs. Further experiments showed that the virus tricks the cell into thinking it is apoptotic debris. This induces blebbing and subsequent uptake of the virus by macropinocytosis. Additionally, automated high throughput siRNA screening was used to screen a large number of infected cells for host genes required for Vaccinia virus uptake. Analysis of the genes identified allowed host factors and processes critical to viral infection to be identified. Expansion of this technique may provide a new source of information on pathogen-host interactions.
Virus Entry -Endocytosis and Penetration
In the second lecture, the next steps in viral infection are described. Endocytosis of plasma membrane bound viruses can occur via a number of mechanisms including caveolar, clathrin, non-clathrin, or lipid raft mediated pathways. The internalized virus is delivered enclosed toin an endosome that may undergoes increasing acidification resulting in acid mediated fusion between the viral envelope and the vesicle membrane. Following membrane penetration, the virus, once again, makes use of cellular machinery such as microtubules and their motors, to transfer its genome to the nucleus. Helenius describes experiments from his lab and others that have deciphered these complex processes.
Cell biology of Virus entry
Viruses are extremely simple and small yet they are responsible for many of the worlds diseases. A vVirus particlees consists of only a genome, a protein coat, or capsid and sometimes a surrounding lipid envelope. To replicate, a virus must successfully enter a host cell, uncoat its genome, and appropriate the host cell machinery to replicate its genome and produce viral proteins. Part 1 of this lecture will discuss ways in which viruses bind to the surface of host cells. Simian Virus 40 which binds to specific cell surface glycolipids, glycolipids and Human Papilloma Virus-16 which binds to sites on filoipodia, are examples of different binding mechanisms. Attachment of viruses to the plasma membrane activates cell signaling resulting in endocytosis of the viral particles. This lecture is appropriate for upper level undergraduate and graduate classes studying virology or endocytosis.
Chemical Glycobiology
A large part of an organisms complexity is not encoded by its genome but results from post-translational modification. Glycosylation, or the addition of sugar molecules to a protein is an example of such a modification. These sugars, or glycans, are often complex, branched molecules specific to particular cells. Cell surface glycans determine human blood types, allow viral infections and play a key role in tissue inflammation
Molecular Biology of Pheromone Perception
Pheromones have evolved to signal the sex and the dominance status of animals and to promote social and mating rituals. In this lecture, I discuss the how pheromone sensing operates in mammals. She discuss the molecular biology of the chemosensory receptors that are involved the first steps of pheromone sensing. At a higher level of complexity, I will discuss a distinct olfactory structure called the vomeronasal organ (VNO) and how it contributes to sex-specific behavioral responses.
Protein Folding and Prion Disease
What do "mad cows", people with neurodegenerative diseases and yeast cells growing happily on a deadly antibiotic have in common? They are all experiencing the consequences of misfolded proteins. Each organism has thousands of different proteins, which define its nature. Like origami paper, they can take the right path and fold into a swan or take the wrong path and fold into a rapacious hawk. The consequences can be deadly, leading to devastating neurodegenerative diseases in humans. Remarkably, a very similar folding process has been discovered in yeast, where it does no harm and can be studied easily and inexpensively.
