Professor Dr. Prapon Wilairat TRF Senior Research Scholar (Biochemistry) Year 2000   Biography and Research Summary   Dr. Prapon Wilairat obtained his B.Sc. (Honours) degree in chemistry from the Australian National University under a scholarship from the Colombo Plan in 1966 and then pursued a Ph.D. in biochemistry at the University of Oregon. USA. with support from the Rockefeller Foundation.   Research in the laboratory of Professor Prapon Wilairat has been guided by the belief that it should be possible to explain living processes in chemical and physical terms. In other words, there is a molecular logic underlying the observed phenomena of cells and organisms, both normal and pathological.   Two diseases found in Thailand have been chosen for study, malaria and thalassemia (a hereditary anemia). These two topics are not unrelated as it is believed (but still not definitively proven) that the existence of thalassemic genes in the human population at polymorphic frequencies (i.e. greater than 1%) is due to protection of heterozygotes against malaria conferred by these genes. The carrier frequency of thalassemia in the Thai population has been estimated to be between 30-40% (18-24 million). with about 500,000 individuals having the disease. On the other hand, although malaria no longer poses a life-threatening menace to the Thai population, the most virulent species, Plasmodium falciparum (accounting for about 50% of all malaria cases), is fast becoming resistant to almost all currently used antimalarial drugs, and thus has the potential to become an important cause for increase in mortality.   The strategy taken to develop novel antimalarials is to focus attention on metabolic processes that are unique to the malaria parasite. The malaria parasite degrades red cell hemoglobin in an organelle known as the acidic food vacuole and detoxifies the undigested toxic heme moiety by converting in into a polymer. Knowledge of the molecular structures of parasite proteases (plasmepsins) in the acidic food vacuole will enable rational design of parasite specific and potent inhibitors. Previous studies from Professor Prapon Wilairat laboratory have shown that acridine compounds can be synthesized to target parasite DNA topoisomerases. As these drugs are also able to accumulate in acidic compartments of the cell, modifications will be made to enable them to inhibit the parasite heme polymerization process. Another approach that will be explored is to tests for compounds that reverse the resistance of Plasmodium falciparum to chloroquine. Proteases are also involved in the invasion of the red cell by the parasite and they can also be exploited as targets of antimalarials.   Understanding of the pathophysiology of thalassemia on molecular terms has lagged behind the exquisite knowledge of the mutations in the affected globin genes. Shortened life span of thalassemic red cells stems from oxidative damage accrued with binding of unmatched globin chains. One of the red cell membrane-bound enzyme affected is the calcium ATPase pump. In vitro models of the thalassemia enzyme will be developed in the hope that an understanding of the molecular changes will lead to therapeutic interventions that can improve the quality of life of the thalassemic patients. Furthermore, it has become increasingly apparent that knowledge of the mutations in thalassemic globin genes is not sufficient to predict the severity of the anemia. The existence of other confounding factors, viz aberrant RNA processing, enhancer mutations, need to be identified.