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Biology
at Millsaps
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.
Wild Type Conidiphore
Mutant Conidiophore
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.
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