Molecular
Biology and Genetics of Viruses
| Malcolm
J. Fraser, Jr.
Professor
Ph.D., Ohio State University
Postdoctoral,
Penn State University, Texas A & M University |
|
The Fraser laboratory merges research in Molecular
Virology and Transgenic Engineering with the particular
goals of advancing applications that improve the human
condition. A major thrust of the research in this
laboratory concerns the utilization of molecular approaches
to understanding and manipulating virus genetics in
ways that permit beneficial transgenic alteration
of the invertebrate hosts of these viruses.
The Home of piggyBac
The Fraser lab has a solid history in the molecular
genetics of Baculoviruses, both from the standpoint
of their exploitation as expression vectors and as
an experimental system for the isolation and analysis
of a unique family of Lepidopteran transposons. Our
laboratory is responsible for the characterization
and development of the piggyBac transposon http://piggybac.bio.nd.edu
, a highly versatile transposon vector with wide
utility for transgenic engineering in a host of eukaryotic
species. This transposon is now facilitating applications
of genetic manipulation and gene characterization
for a wide range of important invertebrate species
that previously had few genetic tools. Important invertebrate
species including the economically significant silkworm,
Bombyx mori , and human disease vectors including
Aedes aegypti and Anopheles stephensi
, may now be transgenically engineered with relative
facility, allowing the analysis of gene identity,
expression, and function.
Research
Emphasis in Molecular Virology
The Molecular Virology aspects of our research include
exploring genetic strategies for suppressing Flavivirus
infections in mosquito cells. Flaviviruses include
the disease agents for Dengue Fever, Yellow Fever,
and West Nile Fever. These are among the most devastating
disease agents of humankind. Our current research
effort involves exploring transgenic approaches to
effecting intracellular immunity to these viruses.
If successful, this approach could be used to eliminate
a mosquito’s capacity to transmit a virus pathogen.
Research Emphasis in Transgenic
Engineering
The Invertebrate Transgenesis aspects of our research
effort involve applications in significant Lepidopteran
and Dipteran insects. Among Lepidopteran insects,
we seek to improve caterpillars as bioreactors for
the production of human therapeutic gene products.
This involves various transgenic approaches that serve
to alter properties of the insect cell that limit
its utility for these purposes, and enhance those
properties that are attractive. Research in this direction
involves a significant effort to uncover strategies
for optimization and controlled expression of genes
in these insect systems.
Among the Dipteran insects, our principal effort involves
the development of strategies for transgenic modification
of mosquito vectors to reduce their capacity for vectoring
human disease agents, particularly Flavivirus disease
agents like Dengue Fever Virus. While transposon vectors
such as piggyBac remain a significant tool
in these transgenesis applications, our lab also explores
alternative approaches to effecting transgenesis of
these mosquito vectors to provide a versatile “toolbox”
for functional genomics in these important disease
arthropods. While Drosophila melanogaster
is not a focus of our research it remains a significant
model genetic system that we utilize to validate our
transgenesis approaches prior to testing them in other
insect systems. |
Occlusion
of Baculovirus virions in the growing paracrystalline matrix
of the polyhedrin protein.
Selected
Publications:
Fraser, M.J.,
L.Carey, K. Boonvisudhi, and H.G.H. Wang. (1995) Assay for
movement of Lepidepteran transposon IFP2 in insect cells
using a Baculovirus genome as a target DNA. Virology 211:397-407.
Elick, T.A., C.A. Bauser & M.J. Fraser. (1996) Excision
of the piggyBac transposable element in vitro is a precise
event that is enhanced by the expression of its encoded
transposase. Genetica 00:1-00.
Elick, T.A., N. Lobo, & M.J. Fraser. (1997) Analysis
of the cis-acting DNA elements required for piggyBac transposable
element excision. Mol Gen Genet 255:605-610.
A.M. Handler, S.D. McCombs, M.J. Fraser, S.J. Saul. (1998)
The lepidopteran transposon vector, piggyBac, mediates germ-line
transformation in the Mediterranean fruit fly. Proc. Natl.
Acad. Sci. USA 95:7520-7525.
T. Tamura, C. Thibert, C. Royer, T. Karda, E. Abraham, M.
Kamba, N. Komoto, J. Thomas, B. Mauchamp, G. Chavancy, P.
Shirk, M. Fraser, J. Prudhomme, and P. Couble. (2000).
Germline transformation of the pilleworm Bombyx mori L.
using a piggyBac transposon-derived vector. Nat. Biotech,
18:81-84.
N. Lobo, A. Hua-Van, X. Li, B. M. Nolan and M. J. Fraser
(2002). Germ live transformation of the yellow fever
mosquito, Aedes aegypti, mediated by transpositional insertion
of a piggyBc vector. Ins. Mol. Biol., 11:133-139.
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