Sérgio Schenkman

sergiopictureFull Professor and
member of the Brazilian Academy of Sciences
Federal University of São Paulo
São Paulo, Brazil
http://www.ecb.epm.br/~sschenkman/

Our laboratory investigates mechanisms involved in growth control and differentiation of protozoan parasites of the Trypanosoma genus. We have studied the signaling events involved in translation initiation and replication control. These include protein phosphorylation and acetylation by protein kinases and acetylases/deacetylases. We have demonstrated that phosphorylation of the eukaryotic initiation factor 2 (eIF2a) is required for nutritional stress-induced differentiation of Trypanosoma cruzi, the agent of Chagas’ disease. We have shown that heme is as a key molecule involved in activation of an endosomal eIF2alpha kinase that phosphorylates eIF2a. Trypanosomes also have four different Target of Rapamycin (TOR) kinases that in eukaryotes control cellular growth. We have found that one of the TOR kinases, containing a unique PDZ domain, is required for survival in hyperosmotic conditions in Trypanosoma brucei, the agent of African Trypanosomiasis. We have also detected variable histone acetylation in differentiated forms and during the T. cruzi division cycle. We found that histone acetylation is related to chromatin assembly during the replication stages of Trypanosomes. In addition, different levels of acetylation were found in cytosolic and mitochondrial proteins, as revealed by proteomic analysis, in different stages of T. cruzi and T. brucei. Taken as a whole, these studies will help to understand how this group of organisms adapt and survive different environmental conditions, which is an essential step in developing novel anti-parasitic drugs.