yeast genetics post-doctoral positions at duke

John McCusker mccusker at abacus.mc.duke.edu
Wed Feb 3 01:28:56 EST 1999


Post-doctoral positions are available to study Phase Variation in
Saccharomyces cerevisiae.
	S. cerevisiae phase variation, which is distinct from pseudohyphal
formation, MAT switching, Ty elements, and silencing, is a novel eukaryotic
microbial model for cellular differentiation and gene regulation.  Phase
variation, which has been extensively characterized in bacteria, involves
the regulation of gene expression through reversible DNA sequence changes
(reviewed in Trends in Genetics 8:422-427 (1992), Adv. Microb. Ecol.
13:263-300 (1993), Curr. Biol. 4:24-33 (1994), Micro. Mol. Biol. Rev.
61:281-294 (1997)); specific genes are phase variable and specific regions
of these genes are highly mutable.  Many phase variable genes are important
for pathogenesis.  One of the most common mechanisms of bacterial phase
variation involves changes in simple repetitive sequences -- similar to a
number of human genetic diseases.
	Although there are other profound phenotypic effects, bacterial
phase variation is commonly manifested by reversible changes in colony
morphology.  In pathogenic fungi such as Candida albicans, "colony
morphology switching" appears to be the fungal equivalent of bacterial
phase variation; as for bacteria, fungal phase variation is important for
pathogenesis.  However, fungal phase variation is not well understood
primarily because of the poor genetics in the human pathogens; for example,
C. albicans is diploid and lacks a sexual cycle.
	I have found that clinical isolates of S. cerevisiae undergo phase
variation.  S. cerevisiae phase variation is likely to play a role in
pathogenesis given (i) the relevance of fungal phase variation to
pathogenesis and (ii) the fact that phase variation is not seen in S.
cerevisiae laboratory strains but is seen in clinical isolates.  The tools
available in S. cerevisiae (genetic analysis, genome sequence, whole genome
analysis) will greatly facilitate the study of phase variation.
	There are multiple phase variable loci in S. cerevisiae with each
locus having distinct phenotypic effects.  For example, in addition to
effects on colony morphology, S. cerevisiae phase variation has profound
effects on phenotype, such as the utilization of novel carbon sources, and
on global gene expression.  This work will be a detailed characterization
of phase variation including (i) the mechanism of phase variation at each
locus and (ii) the regulation by phase variable gene products of gene
expression.  This work will involve whole genome analysis to map the
multiple phase variable loci for positional cloning (1) and to examine
global phase variable gene expression (2).

1.) Winzeler, E.A., D. Richards, A. Conway, A.L. Goldstein, S. Kalman, M.J.
McCullough, J.H. McCusker, D.A. Stevens, L. Wodicka, D.J. Lockhart, and
R.W. Davis. 1998. Direct allelic variation scanning of the yeast genome.
Science 281:1194-1197.
2.) Lashkari, D.A., J.L. DeRisi, J.H. McCusker, A.F. Namath, C. Gentile, S.
Hwang, P.O. Brown, and R.W. Davis. 1997. Yeast micro-arrays for genome wide
parallel genetic and gene expression analysis. PNAS 94:13057-13062.
3.) Lashkari, D.A., J.H. McCusker, R.W. Davis. 1997. Whole genome analysis:
experimental access to all genome sequenced segments through larger scale
efficient oligonucleotide synthesis and PCR. PNAS 94:8945-8947.
4.) McCusker, J.H., K.V. Clemons, D.A. Stevens and R.W. Davis. 1994.
Saccharomyces cerevisiae virulence phenotype as determined in CD-1 mice is
associated with the ability to grow at 42ºC and form pseudohyphae. Infec.
Immun. 62:5447-5455.
5.) McCusker, J.H., K.V. Clemons, D.A. Stevens and R.W. Davis. 1994.
Genetic characterization of pathogenic Saccharomyces cerevisiae isolates.
Genetics 136:1261-1269.

	Extensive molecular biology expertise is required and yeast/fungal
genetics experience is highly desirable.  Start dates are flexible.  Send
curriculum vitae (preferably by e-mail) with contact information for three
references to:

Dr. John H. McCusker
Dept. of Microbiology, 3020
Duke University Medical Center
Durham, NC 27710
e-mail: mccusker at abacus.mc.duke.edu

*****************************************************************************
John H. McCusker, Asst. Prof.
Dept. of Microbiology, 3020
Duke University Medical Center
Durham, NC 27710

phone:  (919) 681-6744
fax:    (919) 684-8735
e-mail: mccusker at abacus.mc.duke.edu






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