Principal Investigator (PI)
IBR-CONICET_UNR Instituto de Biología Molecular y Celular de Rosario
The Foundation is providing £113,599 in support.
Luis Emilio Tavernelli
GSK will give us access to a library of potential bromodomain inhibitors, as well to humans BRD proteins. On the other hand, GSK will let us introduce us in the field of high/medium throughput screening in which we lack expertise.
The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease stands as a fundamental need, since available drugs have significant toxic side effects and a variable efficacy against the life-threatening symptomatic chronic stage of the disease. Bromodomains are protein modules that bind to acetylated lysine residues. Their interaction with histone proteins suggests their role in interpreting the histone code. However, protein acetylation is not a phenomenon restricted to the nuclear proteins. Bromodomain-containing proteins are often found as components of larger protein complexes with roles in fundamental cellular process including transcription, cell cycle regulation, among others. In 2010 two BET bromodomains ligands were described demonstrating that small molecules could inhibit the bromodomain-acetyl-lysine interaction. These molecules display strong phenotypic effects in a number of cell lines and affect a range of cancers in vivo. Recent reports showed that bromodomain inhibitors affect T. cruzi viability and deregulate the expression of stage-specific proteins in T. brucei. The overall objective of this project is to search for bromodomain inhibitors in T. cruzi, by assaying essentials bromodomains previously established in a collaborative GSK-sponsored research project between Esteban Serra’s and Roberto Docampo’s labs. From this project three bromodomains from T. cruzi were selected as putative targets against Chagas disease.