|
|
|
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.
|
|
 |
|
