Cooperation with researcher Charles Rice, winner of the 2020 Nobel Prize in Medicine, is at the root of innovative lines of research at the Oswaldo Cruz Institute (IOC/Fiocruz). The partnership began in the 1980s, when the researcher from IOC Ricardo Galler completed his training in molecular virology in the United States. The two met at the California Institute of Technology (Caltech), where they were both postdoctoral fellows supervised by James Strauss, a reference in the field of virology.
Galler held two postdocs in the US. He arrived at Caltech in 1985, the same year that Rice and Strauss published the first complete genome sequencing of the yellow fever vaccine virus. In 1987, he moved on to Washington University in Saint Louis, where Rice had established his own laboratory. In 1989, Galler was part of the team led by Rice that published one of the first articles to describe the obtainment of synthetic viruses by reverse genetics, applying the methodology to the yellow fever vaccine virus.
Back to IOC, the researcher founded the Flavivirus Molecular Biology Laboratory, where he began research focusing on the use of the yellow fever vaccine virus as an expression vector and on the development of recombinant viral vaccines. Both approaches have reverse genetics as their starting point, which facilitates manipulation of the viral genome, allowing, for example, researchers to insert genes from other pathogens into the genetic code of the yellow fever vaccine virus. In this way, the microorganism begins to express proteins from other infectious agents and can become a platform for immunization against different diseases.
“My focus during the post-doctorate was always the use of the yellow fever vaccine virus as an expression vector, understanding that this would be an important technology for Brazil, which already produced the vaccine and could use it against other diseases”, explains Galler. “Even after completing the post-doctorate, the collaboration with Charles [Rice] was very fruitful for carrying out research, such as the genetic sequencing of the yellow fever vaccine virus in Brazil and virulence studies, and for staff training” , adds the scientist.
The work carried out at the Flavivirus Molecular Biology Laboratory led to an innovative technology for the production of recombinant vaccines, recognized with patents in the United States, Germany, France, the United Kingdom and the Netherlands and applied to produce vaccines against dengue, malaria and HIV. “Galler's training in molecular virology with Rice's group was very important for the creation of a laboratory with this capacity for technological development”, says researcher Myrna Bonaldo, current head of the Flavivirus Molecular Biology Laboratory, who developed the methodology patented together with Galler.
Announced on October 5, the Nobel Prize in Medicine recognized Rice's work in unveiling the last pieces of the puzzle about the hepatitis C virus. The methodology of viral synthesis by reverse genetics was one of the techniques used by the scientist to identify the final sequence of the genome of the microorganism. The Nobel Prize was shared with researchers Harvey Alter and Michael Houghton, considering that the discoveries made by the three scientists were fundamental for the characterization of the pathogen, which allowed the development of diagnostic tests and treatments for the disease.
Announced on October 7, the Nobel Prize in Chemistry recognized the work of researchers Emmanuelle Charpentier and Jennifer Doudna for the development of the CRISPR-Cas9 genome editing method. The tool can be described as genetic scissors, which allows scientists to cut DNA precisely and easily. The cut made at the exact point guided by an RNA guide molecule can be used both to interrupt the expression of a gene and to insert new sequences in the genome. Published just eight years ago, the methodology is considered revolutionary and has already contributed to new cancer therapies, in addition to opening doors to the cure of hereditary genetic diseases.
No IOC, projects use the technique to discover the function of proteins that may play an important role in diseases and to develop new therapies. At the Thymus Research Laboratory, four lines of research are ongoing. Among them is the investigation into the VLA-4 integrin in defense cells called T lymphocytes, which was selected in the Inova F Program Knowledge Generation public noticeiocroz. Present on the cell surface, the molecule acts on the adhesion of lymphocytes to the wall of blood vessels. The process is important for the migration of these cells to sites of infection, but it is also involved in inflammatory diseases such as multiple sclerosis.
The CRISPR-Cas9 methodology is used to investigate other functions of the VLA-4 molecule in the biology of T lymphocytes. “In the first phase of the work, we used CRISPR to silence one of the VLA-4 genes, interrupting the expression of the molecule in the cells. This makes it possible to answer cell biology questions that are important from a clinical point of view”, says researcher Vinicius Cotta de Almeida, head of the Thymus Research Laboratory and project leader. In the next stage of the work, the genetic editing technique will be applied to obtain cell lines with variations in one of the genes that encode VLA-4 that are found in the population, thus investigating possible pathogenic effects.
At the Molecular Virology Laboratory of the IOC, the tool is a bet for new treatments for infections. Researcher Vanessa de Paula, head of the Laboratory, explains that, in this case, the CRISPR-Cas9 genetic scissors are introduced into the cells, but the RNA guide molecule directs the cut to the virus genome. “In virology, the main advantage of CRISPR-Cas9 is the possibility of editing the viral genome and, consequently, of inhibiting virus replication, which opens doors to the cure or treatment of diseases”, says the scientist.
Among the projects initiated, the most advanced targets herpetic keratitis, an eye infection caused by the herpes 1 virus.iocroz. In cell culture, the researchers managed to block viral replication through CRISPR-Cas9. In the next step, the therapy will be evaluated in mice, considered as a model for studying the condition. “We are going to compare CRISPR-Cas9 therapy with standard treatment for herpes viruses”, points out Vanessa, who is coordinating the research.
Cooperation with researcher Charles Rice, winner of the 2020 Nobel Prize in Medicine, is at the root of innovative lines of research at the Oswaldo Cruz Institute (IOC/Fiocruz). The partnership began in the 1980s, when the researcher from IOC Ricardo Galler completed his training in molecular virology in the United States. The two met at the California Institute of Technology (Caltech), where they were both postdoctoral fellows supervised by James Strauss, a reference in the field of virology.
Galler held two postdocs in the US. He arrived at Caltech in 1985, the same year that Rice and Strauss published the first complete genome sequencing of the yellow fever vaccine virus. In 1987, he moved on to Washington University in Saint Louis, where Rice had established his own laboratory. In 1989, Galler was part of the team led by Rice that published one of the first articles to describe the obtainment of synthetic viruses by reverse genetics, applying the methodology to the yellow fever vaccine virus.
Back to IOC, the researcher founded the Flavivirus Molecular Biology Laboratory, where he began research focusing on the use of the yellow fever vaccine virus as an expression vector and on the development of recombinant viral vaccines. Both approaches have reverse genetics as their starting point, which facilitates manipulation of the viral genome, allowing, for example, researchers to insert genes from other pathogens into the genetic code of the yellow fever vaccine virus. In this way, the microorganism begins to express proteins from other infectious agents and can become a platform for immunization against different diseases.
“My focus during the post-doctorate was always the use of the yellow fever vaccine virus as an expression vector, understanding that this would be an important technology for Brazil, which already produced the vaccine and could use it against other diseases”, explains Galler. “Even after completing the post-doctorate, the collaboration with Charles [Rice] was very fruitful for carrying out research, such as the genetic sequencing of the yellow fever vaccine virus in Brazil and virulence studies, and for staff training” , adds the scientist.
The work carried out at the Flavivirus Molecular Biology Laboratory led to an innovative technology for the production of recombinant vaccines, recognized with patents in the United States, Germany, France, the United Kingdom and the Netherlands and applied to produce vaccines against dengue, malaria and HIV. “Galler's training in molecular virology with Rice's group was very important for the creation of a laboratory with this capacity for technological development”, says researcher Myrna Bonaldo, current head of the Flavivirus Molecular Biology Laboratory, who developed the methodology patented together with Galler.
Announced on October 5, the Nobel Prize in Medicine recognized Rice's work in unveiling the last pieces of the puzzle about the hepatitis C virus. The methodology of viral synthesis by reverse genetics was one of the techniques used by the scientist to identify the final sequence of the genome of the microorganism. The Nobel Prize was shared with researchers Harvey Alter and Michael Houghton, considering that the discoveries made by the three scientists were fundamental for the characterization of the pathogen, which allowed the development of diagnostic tests and treatments for the disease.
Announced on October 7, the Nobel Prize in Chemistry recognized the work of researchers Emmanuelle Charpentier and Jennifer Doudna for the development of the CRISPR-Cas9 genome editing method. The tool can be described as genetic scissors, which allows scientists to cut DNA precisely and easily. The cut made at the exact point guided by an RNA guide molecule can be used both to interrupt the expression of a gene and to insert new sequences in the genome. Published just eight years ago, the methodology is considered revolutionary and has already contributed to new cancer therapies, in addition to opening doors to the cure of hereditary genetic diseases.
No IOC, projects use the technique to discover the function of proteins that may play an important role in diseases and to develop new therapies. At the Thymus Research Laboratory, four lines of research are ongoing. Among them is the investigation into the VLA-4 integrin in defense cells called T lymphocytes, which was selected in the Inova F Program Knowledge Generation public noticeiocroz. Present on the cell surface, the molecule acts on the adhesion of lymphocytes to the wall of blood vessels. The process is important for the migration of these cells to sites of infection, but it is also involved in inflammatory diseases such as multiple sclerosis.
The CRISPR-Cas9 methodology is used to investigate other functions of the VLA-4 molecule in the biology of T lymphocytes. “In the first phase of the work, we used CRISPR to silence one of the VLA-4 genes, interrupting the expression of the molecule in the cells. This makes it possible to answer cell biology questions that are important from a clinical point of view”, says researcher Vinicius Cotta de Almeida, head of the Thymus Research Laboratory and project leader. In the next stage of the work, the genetic editing technique will be applied to obtain cell lines with variations in one of the genes that encode VLA-4 that are found in the population, thus investigating possible pathogenic effects.
At the Molecular Virology Laboratory of the IOC, the tool is a bet for new treatments for infections. Researcher Vanessa de Paula, head of the Laboratory, explains that, in this case, the CRISPR-Cas9 genetic scissors are introduced into the cells, but the RNA guide molecule directs the cut to the virus genome. “In virology, the main advantage of CRISPR-Cas9 is the possibility of editing the viral genome and, consequently, of inhibiting virus replication, which opens doors to the cure or treatment of diseases”, says the scientist.
Among the projects initiated, the most advanced targets herpetic keratitis, an eye infection caused by the herpes 1 virus.iocroz. In cell culture, the researchers managed to block viral replication through CRISPR-Cas9. In the next step, the therapy will be evaluated in mice, considered as a model for studying the condition. “We are going to compare CRISPR-Cas9 therapy with standard treatment for herpes viruses”, points out Vanessa, who is coordinating the research.
The non-profit reproduction of the text is allowed as long as the source is cited (Comunicação / Instituto Oswaldo Cruz)
 |
 |
