Medical Students 
Graduate Medical Education
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Ann
L.
Beyer
Degree(s): PhD Graduate School: Vanderbilt University Primary Appointment: Professor, Microbiology, Immunology, and Cancer Biology Research Interests: Ribosomal RNA transcription & processing Email Address: alb4h@virginia.edu |
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Biomedical Sciences Graduate Program(s) Research Description Current research in my laboratory is focused on understanding the basic cellular
processes of ribosomal RNA (rRNA) transcription and ribosome biogenesis. We are
interested in these questions because ribosome synthesis is strictly regulated
and very tightly coupled to cell growth; it is up-regulated in cancer cells and
thus is a target of some chemotherapies.
We use an unusual electron microscopic approach called the Miller chromatin
spreading method that allows us to directly visualize active rRNA genes. All
of our studies are carried out in the yeast, Saccharomyces cerevisiae. In a
typical approach, we first characterize parameters of interest in control cells
and then compare them to the same parameters in cells with a genetic alteration
of interest, such as depletion of a particular protein involved in the process
being studied. This approach allows determination of the role of the protein
in the process being studied. For study of transcriptional regulation, we analyze
such parameters as the number of active rRNA genes in a nucleolus, transcription
initiation and elongation rates for active genes, and chromatin structures correlated
with various genetic activities. For the study of ribosome biogenesis, which
begins while ribosomal RNA is being transcribed, we characterize structural
details of early intermediates in small ribosomal subunit assembly that form
on nascent transcripts. The type of data we obtain is very difficult to obtain
using standard molecular biology approaches due to the multi-copy nature of
rRNA genes and to the very short-lived nature of ribosome intermediates, but
is very informative regarding molecular mechanism and structure. In recent studies
(several cited below), we studied rRNA genes after significantly decreasing
the number of rRNA genes per nucleolus, after interfering with the TOR signaling
pathway, after depleting an RNA polymerase subunit, and after depletion of individual
proteins essential for making ribosomes. Ongoing or planned studies are focusing
on characterization of the composition of several short-lived intermediates
in ribosome assembly, role of topoisomerases in rRNA transcription, role of
chromatin structure and chromatin remodeling in rRNA transcription, and links
between rRNA synthesis and nuclear export of ribosomal subunits. Selected Publications Intranet Profile [To add/update Intranet profile information, read these instructions.]
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