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Biomedical Area

Applications of the science developed at the CIGB have been supported by the results of basic research with significant usefulness for the world scientific community. The study of the pathogenic bacterium Neisseria meningitidis leads to the finding of the highly conserved lpdA gene codifying for P64k protein. This result was a valuable discovery to obtain a protein carrier useful for vaccine design. Appropriate carriers to activate the immune system against poorly immunogenic antigens are highly useful for developing vaccines. After characterizing P64k, the CIGB researchers tested it as a protein carrier conjugated to weak immunogens. These results have born an exceptionally heavy burden of work. P64k protein has been used in experiments on the immune response against cyclic synthetic peptides and envelope fragments of the dengue-1 and dengue-2 viruses. This protein carrier has also been used in a cancer vaccine and a polysaccharide-protein conjugate vaccine. In addition, its safety profile has been already evaluated in humans.
The Laboratory of Molecular Oncology (LMO) has actively been searching for pathways of human oncogenesis inhibition. Starting with a relevant hypothesis and screening a random cyclic peptide phage display library, the LMO?s research staff found a peptide (P15-Tat) with anti-tumor effect and this is now in Phase-I clinical trials. This research provided proof-of-concept that P15-Tat or other molecules that block protein kinase 2 phosphorylation (CK2) could be used in cancer therapy.
The life cycle of the hepatitis C virus (HCV) has been extensively studied by the CIGB?s researchers to explain host-viral interactions. The lack of appropriate protocols to determine subcellular location of HCV in hepatocytes gave rise to investigations of the HCV core protein and nucleocapsid-like particles by electron microscopy. For the first time, the HCV core protein and nucleocapsid-like particles were localized in the nuclei of hepatocytes which are important to understand functions of the viral proteins during HCV infection and to find targets for drug design. Further studies on the localization of HCV components in extrahepatic cells gave some important evidence that will contribute to explain the mechanism of HCV pathogenesis.
Discovery activity at the CIGB has been driven by the researchers? interest to get a deeper understanding of disease mechanisms and in turn to find useful therapeutic and prophylactic drugs. Useful techniques for the study of biological systems and their molecules have been developed for decades at the institution. The development of a methodology to evaluate modeling software is one of the most relevant. The scientific community has reported in more than 60 papers, since 1998, the application of the method for homology modeling, quality evaluation and protein models evaluation. Such methods have been an essential tool for research projects that involve determining protein structure when experimental procedures can not be applied, contributing to reduce the difference between the number of known gene sequences and the number of solved protein structures.
Life sciences scientists usually work with complex biological samples to isolate a few molecules by using validated protocols, and trying to keep the integrity of the separated entities. The development of a technique for intact protein isolation is certainly a most promising direction in proteomics. A procedure for the isolation of proteins by reverse staining was developed by the CIGB?s scientists. The result was a protocol with sensitivity higher than the Coomassie blue acrylamide gel staining method and was faster and adequate for the handling of proteins at low concentrations. The method was improved during 10 years at the Laboratory of Physical Chemistry and optimized procedures for the detection and analysis of proteins were published. This method does not compromise the integrity and activity of unmodified proteins, which is of high significance for analysis and applications of the isolated molecule. These studies have also contributed to a better understanding of the separation mechanism and its applications in proteomics.
Antibody generation and novel production methods are other important fields of investigation for the CIGB researchers. Technological platforms involving expression of recombinant antibody fragments and full antibodies in E. coli, yeast and transgenic plants, and several human antibody fragment libraries, displayed on filamentous phage, are among the most important.
Cuban discoveries and methodologies available in published literature shown that Cuban contributions are firmly rooted in current research methods (the CIGB has published 680 peer-reviewed papers in scientific journals, from 1986 to 2006). It is also worth noting that the CIGB's articles have been cited in more than 3000 papers.