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| Research themes in the TROP Unit |
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Drug development
Trypanosomes are characterized by a unique form
of metabolic compartmentation; the majority of the enzymes
of the glycolytic pathway is sequestered in peroxisome-like
organelles called glycosomes. Therefore the glycolytic
pathway is considered a validated and promising target
for new drugs to be designed. Since many years the TROP
Unit studies the kinetic and structural properties of
the glycolytic enzymes of Trypanosoma brucei
and closely related parasites such as T. cruzi
and Leishmania mexicana, and uses the collected
information for the design of effective and selective
inhibitors by structure-based and catalytic mechanism-based
approaches.
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Glycosome biogenesis
The unique compartmentation of the glycolytic
pathway inside glycosomes, renders these organelles
excellent targets for drug interference. Any drug that
would interfere with the biogenesis of the organelle
would have a direct effect on the parasite's glycolytic
capacity. It is for this reason that the TROP Unit studies
the biogenesis of glycosomes and is characterizing all
the components involved in their biogenesis and their
degradation.
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Glycosome turnover
The different life-cycle stages of the trypanosome
are characterized by strikingly different forms of energy
metabolism. These changes involve both the trypanosome's
mitochondrion and its glycosomes. During the differentiation
of one life-cycle stage into another existing glycosomes
are being degraded by a process called autophagy and replaced
by newly formed glycosomes. The different processes leading
to glycosome biogenesis and degradation are being studied.
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Genomics and proteomics
With the completion of the TriTryp genome-sequencing
projects (T. brucei, T. cruzi and L. major)
, it is now possible to chart the metabolic capacities
of these three organisms and to compare them not only
with each other, but also with the human host. Sequence
analysis, identification of metabolic enzymes and the
elucidation of metabolic capacities by using both bioinformatic
tools and proteomics, are quickly leading to a better
understanding of the metabolic capacities of these organisms.
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