Dr.
Sarah Lea McGuire
Research
in Fungal Genetics and the Eukaryotic Cell Cycle
One
of my earliest interests in biology was in understanding how cancer
cells divide uncontrollably while normal cell division is very
strictly controlled. Sparked by this interest, I began to study
the regulation of the eukaryotic cell cycle as a graduate student
at Baylor College of Medicine. Because cell division is very highly
conserved in all eukaryotes, the genes and proteins which control
it are very similar from fungi to humans. This allows research
on the cell cycle performed in lower eukaryotes to be applied
to higher eukaryotes. I have continued these studies as a member
of the Millsaps College Biology Department.
My
laboratory uses the filamentous fungus Aspergillus nidulans
as a tool to study the eukaryotic cell cycle. Aspergillus nidulans
is an ideal organism for use at a small undergraduate institution,
as it is easily cultured, is non-pathogenic, and has well-defined
genetic and molecular systems. The laboratory is currently funded
by an AREA grant from the National Institutes of Health to generate
and study extragenic suppressors of nimXcdc2
mutations in Aspergillus nidulans. The p34cdc2 protein (encoded
by nimXcdc2) is a protein kinase which controls
entry into mitosis in all eukaryotes, and in Aspergillus nidulans
also controls the G1/S transition as well as progression through
S phase of the cell cycle. The generation of extragenic suppressors
of known mutations is a genetic tool that is often used to identify
genes/proteins which interact with the original mutant protein,
so in our case we are attempting to identify genes/proteins which
interact with the cell cycle regulatory protein p34cdc2. This
project has several phases, the first of which, generation of
the suppressors, has been completed. Candidate suppressors were
screened genetically to determine if they were extragenic, and
all extragenic suppressors have been analyzed and characterized
phenotypically. These will then be cloned and sequenced, and the
sequences compared to those of previously identified genes/proteins.
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Wild Type Conidiphore
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Mutant Conidiophore
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This
analysis has led to the identification of at least three new genes
involved in cell cycle control. Each of these affects the overall
biology of the organism in a different way: One affects cell cycle
control, one affects cell growth and morphogenesis, and one affects
development. These mutations thus give us the tools to study not
only control of nuclear division but also how nuclear division
is related to and interacts with morphogenesis and development.
The facilities and instrumentation and the support for undergraduate
research available at Millsaps College have allowed us to be successful
in these endeavors. The micrographs shown here are scanning electron
micrographs taken at Millsaps of wild type and mutant strains
of Aspergillus nidulans and are one example of the types
of alterations in developmental morphology which we have identified
as being related to cell cycle control. Our task now is to complete
the molecular cloning and biochemical analyses of these mutant
strains and determine how this information affects our understanding
of cell cycle control.