How to conceive a parasite - - the role of centrosome in the cytoskeletal biogenesis of toxoplasma gondii
This proposal a:uns to understand how the structural information for building the cytoskeleton is stored and propagated through cell replication in a protozoan parasite, Toxoplasma gondii. T. gondii is the most conunon cause of congenital neurological defects in humans. This parasite causes diseases only when it replicates, and its replication is entirely dependent on the proper assembly of its cytoskeleton during cell division. Besides its importance in pathogenesis, the cytoskeleton of T. gondii is rich in marvelous and novel structures, and is built in a very unique way. During each round of its replication, the cortical cytoskeletons of the daughters are built to become exact replicas of their mother. Interestingly, this construction process occurs virtually de novo, without any contribution from the existing mother cortical cytoskeletal array. How can such a complicated assembly be precisely reproduced from scratch during each generation? I hypothesize that in order to propagate the structural information for rebuilding the T. gondii cortical cytoskeleton, the information needs to be stored in the centrosome, the only cytoskeletal organelle in T. gondii that is capable of accurately replicating itself and whose replication cycle spatially and temporally correlates with the initiation of daughter cortical cytoskeleton. In this study, I will focus on elucidating the structural and functional role of the centrosome in the initiation of daughter cortical cytoskeleton construction in T. gondii. This study will help us uncover the most crucial steps of the cytoskeletal biogenesis in T. gondii, which will be valuable for not only the rational selection of novel chemotherapeutic targets, but also for understanding the fundamental rules for constructing complicated cytoskeletal structures.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.