TSRI - News & Views, Best of Both Worlds By Eric Sauter When she was 17, Susana Valente, a new assistant professor in Scripps Florida's Department of Infectology, spent a year in Ohio as an exchange student, a good introduction to the United States even though she was already a U.S. citizen. Valente, who was born in Austin, Texas, while her Portuguese parents studied for their Ph.D.s, spent most of her childhood and teenage years in Lisbon. "During my time as an exchange student, I learned that everything is possible in the United States," she said. "If you have the will you can make it. You don't need a diploma, as in Europe. Everybody I spoke with would insist that there were no limits; you could do whatever you wanted to do with your life. That was very interesting." She brought that can-do attitude to her life's passion – science. Valente was introduced to science at an early age through her mother, a professor in Lisbon who started out as a physicist before going into education, and her father, who was a geologist with his own company and consulted with Portugal's national railroad. When Valente was young, her mother would take her and her siblings – she has two sisters and a brother – to various scientific conferences. "I was surrounded by the mentality of science," she said. "We were raised with science – that empirical attitude – so I was attracted to logic and the rigors of proof. When I was a kid if I couldn't understand something I would get pretty upset and my mother would explain, 'Hey, it's just a chemistry problem.' But for me, things had to make sense." In Portugal, like in other European countries, students choose what profession to pursue when they reach ninth grade. For Valente, the decision seemed ready-made: "I was better in chemistry and biology and not so gifted in philosophy. The choice was easy." In the end, Valente managed to gain the equivalent of three master's degrees in science, studying at the University of Paris, Montfort University in Leicester (U.K.), the Institut Cochin Genetique Moleculaire, Paris, and Hogeschool West-Brabant in the Netherlands. After all this travel and learning, Valente eventually decided to specialize in virology. "I decided on virology because I was very curious about the intricate ways that viruses exploit their host cell, besides I loved to look at acutely infected HIV cells under the microscope!" she said. "It was fascinating, it was exciting, and there was actually money available for research. What I liked most of all, and still do, is that viruses make you think in directions you're not expecting. The virus is in a relationship with the cell and you have to follow where it will lead. Because of that, you're always renewing yourself and your science." After postdoctoral work at Columbia University, Valente looked for a place where she could follow where the research led her. She found Scripps Florida. Finding New Ways to Stop HIV At Scripps Florida, Valente has focused on investigating those parts of the host machinery that HIV needs to complete its replication in the body. In a study published last October in the journal Molecular Cell, Valente and her colleagues focused on genetic screening for genes and even gene fragments to identify those host factors that were critical to HIV replication and those that might inhibit it. What she found was that an initiation factor called eIF3f (eukaryotic initiation factor 3 subunit f), which is key to turning a gene's message into a protein by translating messenger RNA (mRNA) into an amino acid chain, also had the power to block HIV replication by reducing the processing of the viral messenger RNA. Without mRNA, the virus cannot successfully replicate, making these factors a tantalizing target for potential therapeutics. Although complex in its details, in a lot of respects the paper is very simple, Valente said. "I wanted to find cell factors that could block HIV replication, so we took an approach involving the genetic screen of certain cDNA libraries, and with one of those screens we identified a pair of factors that blocked the virus," she said. "The study also reveals several other factors involved in the viral RNA processing mechanism that we weren't aware of before. Even better, we can manipulate them for our own purposes without damaging the cell activity, which is very important if your eventual goal is to look for lead drug candidates." This is an area that she intends to focus on at Scripps Florida. "Now we're trying to discover with more detail the mechanism by which the identified factors block HIV-1 replication and screen for compounds that will affect the virus and not the host cell," she said. "We also want to pursue the search for more of these factors that are critical for viral replication by continuing the genetic screens that have already proven successful." It has been a challenge starting her own laboratory but, as it turns out, not an onerous one. "Things work out," she said. "You start working and producing data, and it's this mountain you have to climb, but you do it. Scripps Florida has made it easier. Everybody is here to help. Besides, it's Florida and it's a beautiful place to live and work. We all get seduced by Florida." Send comments to: mikaono[at]scripps.edu



	Vol 10. Issue 10 / March 22, 2010



Best of Both Worlds By Eric Sauter When she was 17, Susana Valente, a new assistant professor in Scripps Florida's Department of Infectology, spent a year in Ohio as an exchange student, a good introduction to the United States even though she was already a U.S. citizen. Valente, who was born in Austin, Texas, while her Portuguese parents studied for their Ph.D.s, spent most of her childhood and teenage years in Lisbon. "During my time as an exchange student, I learned that everything is possible in the United States," she said. "If you have the will you can make it. You don't need a diploma, as in Europe. Everybody I spoke with would insist that there were no limits; you could do whatever you wanted to do with your life. That was very interesting." She brought that can-do attitude to her life's passion – science. Valente was introduced to science at an early age through her mother, a professor in Lisbon who started out as a physicist before going into education, and her father, who was a geologist with his own company and consulted with Portugal's national railroad. When Valente was young, her mother would take her and her siblings – she has two sisters and a brother – to various scientific conferences. "I was surrounded by the mentality of science," she said. "We were raised with science – that empirical attitude – so I was attracted to logic and the rigors of proof. When I was a kid if I couldn't understand something I would get pretty upset and my mother would explain, 'Hey, it's just a chemistry problem.' But for me, things had to make sense." In Portugal, like in other European countries, students choose what profession to pursue when they reach ninth grade. For Valente, the decision seemed ready-made: "I was better in chemistry and biology and not so gifted in philosophy. The choice was easy." In the end, Valente managed to gain the equivalent of three master's degrees in science, studying at the University of Paris, Montfort University in Leicester (U.K.), the Institut Cochin Genetique Moleculaire, Paris, and Hogeschool West-Brabant in the Netherlands. After all this travel and learning, Valente eventually decided to specialize in virology. "I decided on virology because I was very curious about the intricate ways that viruses exploit their host cell, besides I loved to look at acutely infected HIV cells under the microscope!" she said. "It was fascinating, it was exciting, and there was actually money available for research. What I liked most of all, and still do, is that viruses make you think in directions you're not expecting. The virus is in a relationship with the cell and you have to follow where it will lead. Because of that, you're always renewing yourself and your science." After postdoctoral work at Columbia University, Valente looked for a place where she could follow where the research led her. She found Scripps Florida. Finding New Ways to Stop HIV At Scripps Florida, Valente has focused on investigating those parts of the host machinery that HIV needs to complete its replication in the body. In a study published last October in the journal Molecular Cell, Valente and her colleagues focused on genetic screening for genes and even gene fragments to identify those host factors that were critical to HIV replication and those that might inhibit it. What she found was that an initiation factor called eIF3f (eukaryotic initiation factor 3 subunit f), which is key to turning a gene's message into a protein by translating messenger RNA (mRNA) into an amino acid chain, also had the power to block HIV replication by reducing the processing of the viral messenger RNA. Without mRNA, the virus cannot successfully replicate, making these factors a tantalizing target for potential therapeutics. Although complex in its details, in a lot of respects the paper is very simple, Valente said. "I wanted to find cell factors that could block HIV replication, so we took an approach involving the genetic screen of certain cDNA libraries, and with one of those screens we identified a pair of factors that blocked the virus," she said. "The study also reveals several other factors involved in the viral RNA processing mechanism that we weren't aware of before. Even better, we can manipulate them for our own purposes without damaging the cell activity, which is very important if your eventual goal is to look for lead drug candidates." This is an area that she intends to focus on at Scripps Florida. "Now we're trying to discover with more detail the mechanism by which the identified factors block HIV-1 replication and screen for compounds that will affect the virus and not the host cell," she said. "We also want to pursue the search for more of these factors that are critical for viral replication by continuing the genetic screens that have already proven successful." It has been a challenge starting her own laboratory but, as it turns out, not an onerous one. "Things work out," she said. "You start working and producing data, and it's this mountain you have to climb, but you do it. Scripps Florida has made it easier. Everybody is here to help. Besides, it's Florida and it's a beautiful place to live and work. We all get seduced by Florida." Send comments to: mikaono[at]scripps.edu		"I decided on virology because I was very curious about the intricate ways that viruses exploit their host cell," says Scripps Florida Assistant Professor Susana Valente. (Photo by James McEntee)