William Jackson, PhD
Assistant Professor
Microbiology and Molecular Genetics
Medical College of Wisconsin
Research Focus: Viral Genetics, Virus-Host Cell Interactions
PhD: University of California, Berkeley (1999) Molecular and Cell Biology |
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My lab studies how viruses interact with their host cells, and we go about this by using the genetic diversity of one viral family as a tool. These studies utilize the family Picornaviridae, which encompasses viruses as diverse as Poliovirus, the causative agent of poliomyelitis; Rhinovirus, a major agent of the common cold; Hepatitis A virus, which causes acute liver disease; and Foot and Mouth Disease Virus, an economically devastating disease of livestock. Despite such an incredible diversity of disease, cellular effects, and viral host, these viruses are remarkably similar in genetic organization and sequence.
This begs the question of how relatively subtle genetic differences among viruses can lead to enormous differences in the viruses' interactions with cells and the outcome of infections. Using Poliovirus and Rhinovirus as starting points, our lab analyzes important phenotypic differences between viruses in the same family or species. In particular, we are interested in viral subversion of innate immune pathways such as autophagy, viral mechanisms to prevent immune surveillance such as inhibition of cell secretion, cell-to-cell viral transmission pathways, and intracellular virus replication in general.
In addition, we are using yeast as a model cell in which we can express viral proteins and observe effects on the cell with similarities to effects on mammalian cells. We also use clonally differentiated cell lines with different infection phenotypes to determine which host changes can alter viral growth. These approaches allow for simple "host genetic" analysis of the genetic pathways being altered by viral products. The goal of this research is ultimately an understanding of how subtle genetic differences in viruses can lead to evasion and subversion of the immune response, development of viral drug resistance, and evolution into new species.
Cellular effects of picornovirus.
A. Arrows show unusual double-membraned structures in rhinovirus 14 infection. Arrowheads designate virions in and near the structures.
B, C, D. During poliovirus infection, unusual structures near the cell surface label with the autophagy maker protein GFP-LC3 and PV capsid protein.
Cellular effects of picornovirus.
A. The autophagy marker GFP-LC3 and the protein LAMP-1 co-localize in response to autophagic induction by Rapamycin or Tamoxifen treatment.
B. During poliovirus infection, GFP-LC3 and the protein LAMP-1 co-localize in a manner reminiscent of autophagy.
C. These effects can be replicated using two different rhinovirus species.
Recent Publications
Kirkegaard K, Jackson WT. Topology of double-membraned vesicles and the opportunity for non-lytic release
of cytoplasm. Autophagy. 2005 Oct-Dec;1(3):182-4. Epub 2005 Oct 30.
Abstract
Jackson WT, Giddings TH Jr, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR, Kirkegaard K. Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol. 2005 May;3(5):e156. Epub 2005 Apr 26.
Abstract
Kirkegaard K, Taylor MP, Jackson WT. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nat Rev Microbiol. 2004 Apr;2(4):301-14. Review.
Abstract
Contact Information
Email: wjackson@mcw.edu
Phone: 414-456-8456
Room: BSB-204