Inherited human peroxisomal diseases such as Zellweger syndrome often lead to problems in neuronal development
and to neurodegeneration. In addition to containing enzymes catalyzing reactions involving molecular oxygen and
for metabolising hydrogen peroxide, peroxisomes are also involved in degrading fatty acids. An established model
organism for studies on neural development and maintenance is represented by the nematode Caenorhabditis
elegans. The neural network in C. elegans has been thoroughly studied, and its genome has now been sequenced.
However, little is known about peroxisomes or fatty acid degradation in this organism. Hence, as a first step in
assessing whether nematodes could serve as an appropriate model system for studying the potential role of
peroxisomes and peroxisomal functions in neurodegeneration, more information must be obtained about the
nematode peroxisomal compartment as well as the identity of the biochemical processes contained therein. To
identify nematode ?-oxidation protein genes, a system based on the yeast Saccharomyces cerevisiae has been
developed.
We plan
to clone novel C. elegans open reading frames postulated to encode ?-oxidation enzymes;
to produce these novel proteins and enzymatically characterise them;
to clarify their subcellular location using reporter proteins expressed in yeast cells;
to demonstrate a physiological function of these novel nematode proteins by expressing them in appropriate yeast
mutants and monitor functional complementation