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Carolina Salguero

College: Hunter College
Awards: National Science Foundation Graduate Research Fellowship, 2012

Taking the H (Harm) Out of HIV

The human immunodeficiency virus (HIV) is a single strand of trouble. A bundle of viral RNA invades host cells, hijacks the cells' machinery to copy itself and assembles new viral particles to invade other cells. Left unchecked, HIV is a death sentence. Drugs can prevent it from developing into full-blown AIDS, but the virus survives, ever waiting for the chance to emerge and wreak havoc.

Carolina Salguero (Hunter College, BA in biochemistry, minor in economics, 2011), now a doctoral student in molecular and cell biology at Harvard University, sees a way to render HIV harmless..

The virus has only nine genes (compared to more than 500 in a bacterium and more than 20,000 in a human). Three of them - named gag, pol and env - make proteins involved in infrastructure and replication of new viral particles; the other six code for proteins that control HIV's ability to infect a cell and enhance replication.

When two of the genes, gag and pol, are not translated in the proper ratio - that is, when the production of proteins coded by those genes is knocked awry - the assembly, replication and infectivity of new viral particles are impaired.

The National Science Foundation has granted Salguero a 2012 Graduate Research Fellowship to explore this approach at neutering HIV. She will undertake structural and functional studies to reveal the mechanisms by which retroviruses, like HIV, use three-dimensional RNA as a regulatory structure that maintains the correct ratio of gag and pol.

"I hope this approach will lead to a breakthrough," she says. Salguero has support not only from the National Science Foundation - whose $126,000 grant over three years is the most prestigious award a graduate student in the STEM disciplines (science, technology, engineering and mathematics) can win - but also from Merck, the pharmaceutical giant. "They see the potential in our research," she says.

Salguero took the long road to get to the lab. When she was 12, living in her native Bogotá, Colombia, she read about how the Human Genome Project would unlock the basic mechanism behind the human species, and she longed to take part in that quest. By the time she finished a public technical high school, the human genome had been decoded, but her interest in math, chemistry and biology had only grown. "I knew this was the field I wanted to be in," she says.

When she graduated at 16, her parents sent her to the United States to study. "My father was unable to attend high school because he was obligated to work to help support his family since the age of 9," Salguero says. Although he could not pay to educate his eight children, "he relentlessly encouraged us to pursue a college education."

It took her 11 years to finish her undergraduate degree because she needed to work full time to support herself. "Because I paid for my own college education, I always made an effort to maximize my learning experience," she says. She earned an associate degree in California, managed a college preparation center in Miami and worked as a private tutor for K-12 students in New York City in topics ranging from algebra to chemistry to personal finance.

Her baccalaureate training set her on the path to the doctoral work she is undertaking at Harvard. She started at Hunter College in 2008 and got into laboratory research with the support of federally funded programs like Minority Access to Research Careers, Minority Biomedical Research Support and the Research Initiative for Scientific Enhancement. This led to three years of lab work at Hunter.

For two years, she worked with chemistry Associate Professor Akira Kawamura, assisting in a graduate student's research. In one self-contained project, she used a photoactive probe to selectively label and separate adenine-binding proteins from a complex protein mixture. Kawamura's lab uses "photoaffinity-labeling" to find targets for therapeutic drugs. "Identification of new proteins targeted by small molecules is important because it opens up new opportunities for therapeutic intervention of various diseases using small molecules," his website says.

Salguero says that this research developed her critical-thinking skills, honed her basic laboratory skills and got her fascinated with proteomics (the study of expressed proteins under defined conditions), "especially in the intrinsic relationship of protein structure and function."

In her last year at Hunter, Salguero also worked with structural biology Professor Nancy Greenbaum, an expert in RNA, investigating the features of an RNA loop structure that forms prior to gene splicing. "Working with Doctor Greenbaum, I was able to appreciate that answering biochemical and biophysical questions not only requires the analysis of the nature and structure of the molecules involved, but it also involves a deep analysis of the dynamics and energetics of chemical and biological interactions," she says.

Salguero is a CUNY Jonas E. Salk Scholar, and she was the first Hunter student to receive the Rosalyn Yalow Achievement in Science Award. She also had two significant summer internships. In 2009, she was at Harvard, where she used nuclear magnetic resonance to solve the structure of the RNA that regulates the gag and pol ratio in Murine Leukemia Virus (MLV). She conducted experiments of mutant constructs, which helped demonstrate that regulation of the gag and pol ratio in MLV requires a change in the shape of the regulatory RNA. This led to a third-authorship on a paper.

Her other summer internship was at Yale, where she purified the human blue pigment opsin, one of the photoreceptors responsible for color vision, using nanoscale lipid disks. She continued working to purify the blue opsin on weekends during the fall semester while she was taking classes and working in a lab at Hunter. Her work at Yale led to a first-authorship on a manuscript that is in preparation.

Although completion of her doctoral research is perhaps four years away, Salguero is considering education beyond that - perhaps a master's in public health, which would enable her to better combine her knowledge of the molecular basis of infectious diseases with real-world implications for underprivileged populations.