George A. Marzluf
Professor
Phone: 614-292-9471
Fax: 614-292-6773
email: marzluf.1@osu.edu
Webpage: None
Research Interests:
The research program of my laboratory is directed at an understanding
of the regulation of gene expression in eukaryotic organisms. We employ
parallel biochemical, genetic and molecular approaches to study genetic
regulation in the model lower eukaryote, Neurospora crassa. Of particular
interest is the molecular mechanisms by which major regulatory genes
exert control over entire sets of unlinked structural genes. Our work
is focused upon two regulatory circuits, one which controls the expression
of many enzymes of multiple pathways central to nitrogen metabolism,
and a second control circuit which governs multiple genes of sulfur
assimilation. In each of these circuits a major control gene encodes
a nuclear DNA-binding protein that regulates the expression of an entire
family of related but separate genes. We have cloned, using recombinant
DNA techniques, the important regulatory genes of these control circuits
as well as representative structural genes. Our work is devoted to an
analysis of the regulatory proteins, their expression and structure,
and DNA binding activity, as well as deciphering the DNA elements recognized
by each transcription factor. Site-directed mutagenesis and protein
engineering experiments are used to manipulate these genes which are
then analyzed in vitro and in vivo to understand the mechanisms responsible
for specific protein-protein and DNA-protein interactions.
Our laboratory also is investigating a serious human genetic disease,
Kennedy's disease, for which no treatment is available. Kennedy's disease
results from an expanded glutamine stretch in the androgen receptor,
a DNA-binding protein that controls gene expression in response to hormonal
stimulation. The DNA binding activity of the androgen receptor is similar
to regulatory proteins we have studied in detail in the model eukaryote.
The altered androgen receptor protein causes a severe neurological syndrome,
leading to nerve cell death and serious muscle loss. We are comparing
protein-protein interactions of the normal androgen receptor with those
of the altered receptor from patients to determine the basis for the
severe disease state.
Selected publications from the last 5 years:
Mo., X. and Marzluf , G.A. (2003) "Cooperative action of the NIT2
and NIT4 transcription factors upon gene expression in Neurospora crassa." Curr,
Genet. 42, 260-7.
Harrison, K.A. and Marzluf , G.A. (2002) "Characterization of DNA
binding and the cysteine rich region of SRE, a GATA factor in Neurospora
crassa involved in siderophore synthesis." Biochemistry 41, 15288-95.
Marzluf , G.A. (2001) "Metabolic regulation in fungi." Applied
Mycology and Biotechnology (Eds. G. Khachatourians and D. Arora)
pp. 55-72.
Feng, B. and Marzluf , G.A. (2000). "ASD4 a new GATA factor of Neurospora
crassa, displays sequence-specific DNA binding and functions
in ascus and ascospore development." Biochemistry 39,
11065-11073.
B. Tudzynski, V. Homann, B. Feng, and Marzluf
, G.A. (1999). "Isolation,
characterization, and disruption of the areA nitrogen regulatory gene
of Gibberella fukikuroi." Mol. Gen. Genetics 261:
106-114.
L. W. Zhou, and Marzluf , G.A. (1999). "Functional analysis of
the two zinc fingers of SRE, a GATA-type factor that negatively regulates
siderophore synthesis in Neurospora crassa." Biochemistry 38:
4335-4341.
Y. Tao, and Marzluf , G.A. (1999). "The NIT2 nitrogen regulatory
protein of Neurospora: expression and stability ofnit-2 mRNA
and protein." Curr. Genet. 36: 153-158.
Zhou, L.W., H. Haas, and Marzluf , G.A. (1998) "Isolation and
characterization of a new gene, sre, which encodes a GATA-type regulatory
protein that controls iron transport in Neurospora crassa." Mol.
Gen. Genetics 259: 532-540.
Tao, Y. and Marzluf , G.A. (1998) "Analysis of a distal cluster
of binding elements and other unusual features of the promoter of the
highly regulated nit-3 gene of Neurospora crassa." Biochemistry 37:
11136-11142.
Feng, B. and Marzluf , G.A. (1998) "Interaction between major
nitrogen regulatory protein NIT2 and pathway-specific regulatory factor
NIT4 is required for their synergistic activation of gene expression
in Neurospora crassa." Mol. Cell. Biol. 18: 3983-3990.
Coulter, K.R. and Marzluf , G.A. (1998) "Functional analysis of
different regions of the positive-acting CYS3 regulatory protein of Neurospora
crassa." Curr. Genet. 33: 395-405.
Tao, Y. and Marzluf , G.A. (1998) "Synthesis and differential turnover
of the CYS3 regulatory protein of Neurospora crassa are subject
to sulfur control. of Neurospora crassa." J. Bacteriol. 180:
478-482.
