Nucleic Knowledge

What does it take to turn a once-terminal diagnosis into a manageable chronic health condition? In the four-plus decades since the onset of the HIV/AIDs epidemic, researchers have worked to discover the deadly virus’ secrets and understand what makes HIV-1 so challenging to treat. That progress has proved life-sustaining for patients, but scientists around the world continue to work in pursuit of a cure.

Within Florida State University’s Department of Biological Science, assistant professor Ashwanth Francis is leading the next generation of research to determine how HIV integrates itself into the nucleus of a human cell and becomes part of an individual’s DNA. What his team learns prompts further investigation into earlier identification of HIV-infected cells and how to arrest the virus’ replication more quickly.

“In the context of human evolution, understanding how retroviruses such as HIV can integrate themselves and become part of our human genome is extremely important, not only for present-day treatment options and fundamental ideas about the virus, but also for propelling research forward in anticipating how this virus changes with us,” Francis said.

Despite ongoing research, HIV remains a unique scientific phenomenon. Individuals infected may manifest a variety of complex symptoms including fever, headache, sore throat, and rash as the virus spreads rapidly — and stealthily — throughout the body.

When infiltrating a human cell, HIV camouflages itself as organic substances called nucleic acids that are transported from the cytoplasm, a gelatinous liquid that fills a cell, to gain access to a cell’s nucleus and thereby its genetic material, or DNA. Francis’ work focuses on the cloaking mechanism processes and how the virus evolves over the course of its journey within a cell.

“As the virus travels through the pores of a nucleus, it gathers host cellular proteins that stick to it, allowing HIV to infect a cell and start the replication process,” he explained. “Once the virus integrates itself into the DNA of a cell’s nucleus, it controls the cell’s regeneration and copies itself, spreading throughout the body.”

Francis was a child when HIV began sweeping the world, and he saw the devastating impact it had on people in developing nations including his hometown of Tamil Nadu, India. He was motivated to focus his fascination with science into a career helping advance knowledge of the virus.

“As an undergraduate, I began preliminary work on HIV while working in a pediatric ward in India,” Francis said. “I became attached to the work and decided to pursue a doctoral degree to continue my learning efforts.”

At the time, India did not have the technology available to facilitate Francis’ work, so he searched for educational opportunities abroad — a scholarship offer from Scuola Normale Superiore, a public university in Pisa, Italy, soon followed.

“I spent the next eight years adjusting to Italian culture and utilizing as many resources as possible to develop microscopy methods, which now allow us to see the HIV virus in its environments within a cell,” Francis said.

Upon earning his doctorate in 2014, Francis worked as a postdoctoral researcher and assistant professor at Emory University, in Atlanta, Georgia, before joining FSU’s faculty in March 2021.

Today, Francis and his team seek new technologies that allow them to better analyze HIV interactions with its host-environment at high-resolutions using FSU’s FEI Titan Krios transmission electron microscope. Francis plans to incorporate fluorescent tags he has developed into his lab work to help identify virus structures that correlate to HIV-1 infection. Developing new means to study the virus paves the way for new drug development, cultivating a pipeline of scientific efforts leading back to patient care.

“How the nucleus of a cell functions, which holds our DNA together, is still a big mystery in the science world, so my work allows scientists to discover exciting answers to complex questions regarding interactions between viruses and a cell’s nucleus,” Francis said.

“Francis brings immense energy and enthusiasm for science to our department. He is open about his research and always eager to share results. Analyzing data and discussing its meaning are my favorite things about doing science, so when Francis appears in my office doorway with an excited look on his face, I know I’m about to see something good.”

— Scott Stagg, Professor of Biological Science

The Titan microscope is among many cutting-edge technologies at FSU that allow Francis and others in the Stagg Laboratory, led by professor of biological science Scott Stagg, to capture 3-D images of how HIV changes the architecture of a cell’s nucleus. Stagg and Francis are co-primary investigators on projects that focus on developing new techniques that reveal the molecular details of how cell proteins and the virus interact within a single cell’s architecture.

“Francis brings immense energy and enthusiasm for science to our department. He is open about his research and always eager to share results,” Stagg said. “Analyzing data and discussing its meaning are my favorite things about doing science, so when Francis appears in my office doorway with an excited look on his face, I know I’m about to see something good.”

Because of the work of generations of scientists like Francis, the World Health Organization notes nearly 95 percent of people with HIV today can take prescribed antiretroviral treatment and live long, healthy lives with effectively no risk of transmitting the virus to others.

Hannah Fulk is an FSU alumna who earned a bachelor’s degree in public relations in 2022. She is currently pursuing a master's degree in media and communications studies with a certification in digital video production and is set to graduate in May 2024.