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Jean E. Feagin, Ph.D.
Mission
Dr. Feagin studies mechanisms that regulate gene expression and function in apicomplexan parasites, with an emphasis on identifying differences between parasites and their human hosts that might be exploited for disease intervention.
Research
The Feagin laboratory studies gene
expression mechanisms in apicomplexan
parasites. We have studied ribosome
biogenesis and function in Plasmodium
falciparum, focusing mostly on the
structure of the unusual P. falciparum
mitochondrial ribosomal RNAs, which are
encoded as short fragments rather than
contiguous molecules. A total of 34 small
transcripts derive from the mitochondrial
genome, 25 of which can be assigned to
specific regions of rRNA. Many of them
encoded directly adjacent to other genes,
with no intervening sequence and we have
evidence for polycistronic transcription.
How they are cleaved from the precursor is
unknown but great precision must be needed.
We have recently embarked on analysis of pre-mRNA splicing
in P. falciparum. Introns in the malaria parasite lack discernable
branchpoint motifs. By experimentally mapping branchpoints, we have found that
P. falciparum introns can have more than one branchpoint and that some are us
instead of As.
In collaboration with the Parsons lab,
Dr. Feagin and her colleagues are examining protein trafficking pathways to an
apicomplexan organelle related to chloroplasts. This project employs
Toxoplasma gondii, which is more amenable to genetic manipulation than is
Plasmodium. While superficially disparate from the Plasmodium
project, the trafficking project nonetheless overlaps in its focus on
organelles.
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Themes |
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Organelle Biogenesis |
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Regulation of gene expression |
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Molecular genetics of
apicomplexans |
Program Accomplishments
Our work has focused on the
biogenesis and function of the mitochondrion
and apicoplast, especially as relates to
protein synthesis in the organelles and
trafficking cytoplasmically synthesized
products to them. Both organelles have
potential as drug targets. We have
recently begun examining:
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Identified and characterized the
mitochondrial RNA polymerase gene and its expression |
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Participated in initial testing of
potential antimalarial compounds |
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Completed mapping for 34 putative
mitochondrial rRNA fragments and assignment of 25 to rRNA structure. The
P. falciparum mitochondrial rRNAs correspond well to the small but
contiguous mitochondrial rRNAs of C. elegans and when modeled on
crystal structures of bacterial ribosomes, they cluster on adjoining faces
of the large and small subunit. |
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With collaborators in the Parsons lab,
we have analyzed trafficking of membrane proteins to the apicoplast in T.
gondii, and have obtained evidence for vesicular trafficking in that
pathway. |
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Identified branchpoints in P.
falciparum introns for the first time, showing that there are more than
one per intron, and that some are Us rather than the canonical As.
Identified potential alternate binding ligands for key splicing proteins. |
The National Institutes of Health (NIH) currently provides support for Dr. Feagin’s research.
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