In the 1995 movie Outbreak, a fictional, Ebola-like virus emerges in Zaire (now the Democratic Republic of Congo) and spreads to the United States. As a teenager growing up in Melbourne, Australia, Lachlan Gray was inspired by the movie. Working with dangerous viruses like Ebola “always sparked my curiosity, and I guess I wanted to figure out how something so small and insignificant can ultimately lead to the downfall of an organism as complex as the human,” he says.
Today, Gray, a senior postdoctoral fellow at the Burnet Institute in Melbourne, studies a virus—HIV—which, while it is no longer the death sentence it was when it was first discovered 3 decades ago, is proving extremely difficult to eradicate. Gray is one of a small number of scientists worldwide trying to shed light on how HIV spreads to the brain, where it can cause neurocognitive disorders and establish viral reservoirs that make it resistant to the available drugs. Gray, who is 34, has already won awards for his work while balancing the demands of research with a strong commitment to family.
Patients are 'living with the virus longer, so there is a greater opportunity for the virus eventually to take off in the brain.'
An interest in dangerous viruses
Gray obtained a Bachelor of Science degree in 2002 from the University of Melbourne with majors in virology, immunology, and genetics. He spent the following year in Paul Gorry’s HIV Molecular Pathogenesis Laboratory at the Burnet Institute, doing an honor’s research project supported by an award from The Australasian Society for HIV Medicine. During that first research experience, Gray worked to understand why a cohort of patients infected with an attenuated strain of HIV-1—the Sydney Blood Bank Cohort—had never progressed to full-blown AIDS. “I was really trying to characterize what is it about their virus that delays progression or stops progression, and can we exploit that for the use of the wider HIV-infected population,” Gray says. Gray would go on to do a Ph.D. in Gorry’s lab, but it wasn’t a decision he made lightly. His hesitation was partly a result of self-doubt, but he was also concerned about work-life balance. Gray met his wife when he was in his late teens and describes himself as a family man. He wanted to make sure he could commit sufficient time and dedication to a Ph.D. project while reserving time for family. Before embarking on a Ph.D., you must consider “whether that’s going to work with your life expectations and what you want to do outside of work,” he says.
So, Gray delayed his Ph.D., spending another year in Gorry’s lab as a research assistant. His work-life balance concerns were assuaged, and during these 2 years, he “showed that he was extraordinarily capable in the lab and produced stunning data that we published in several papers that have had considerable impact in the field,” Gorry writes in an e-mail to Science Careers. Gray went on to win a Dora Lush Biomedical Research Postgraduate Scholarship from the Australian National Health and Medical Research Council (NHMRC).
Homing in on HIV in the brain
All HIV-infected patients harbor virus within their brains, although nowadays only 10 to 20% show symptoms of brain infection or neurocognitive impairment, Gray estimates. That’s down from about 50% prior to the advent of combination antiretroviral therapy, but the problem of HIV brain infection is expected to get worse again, Gray says, because patients are “living with the virus longer, so there is a greater opportunity for the virus to … take off in the brain.” Many currently available anti-HIV drugs are unable to penetrate into the brain, and the drugs that can are not as effective at combating infection there as they are in other parts of the body, Gray says.
As a Ph.D. candidate, Gray investigated the properties of the virus that permit infection and damage in the brain by comparing brain virus with blood virus from the same patient. He wanted to know “what [we can] learn in terms of really characterizing … brain virus, and how we can use that knowledge to … prevent brain infection or alleviate symptoms or pathogenesis,” Gray says. Gorry, who continues to collaborate with Gray, writes that “Lachlan became expert at molecular and functional analysis of HIV-1 envelope glycoproteins, and he showed how these glycoproteins evolve in viruses isolated from patients during disease progression, and also within the brain.”
For his postdoc, which he supported with an NHMRC postdoctoral fellowship, Gray chose to go to the Monash University lab of Steve Wesselingh. Gray’s decision to stay near home, instead of traveling overseas, was deliberate. While he acknowledges the benefits of doing a postdoc abroad, he prioritized settling down and starting a family. He tried to compensate for the lack of overseas experience by trying to be as productive as possible.
HIV’s ability to hide in latent viral reservoirs, and then to rebound from them as soon as the drugs are stopped, is a major barrier to curing HIV/AIDS and to the even more ambitious goal of eradicating HIV. During his postdoc, Gray studied how HIV replicates in brain cells, focusing on the region of the virus—the promoter—responsible for kick-starting the production of all the viral proteins. His work won 19 awards, including the Special HIV Cure Prize given out at the 2013 International AIDS Society meeting in Malaysia; the award recognized work in which he identified mechanisms that allow HIV to establish reservoirs within the brain.
Weighing his options
Gray has found his research niche. “Not a lot of people … work on HIV brain infection,” and that, he says, gives him more space to become a leader and improves his chances of getting funded. Gray is applying for fellowships to help him establish an independent group, including the Career Development Fellowship from NHMRC and the Mathilde Krim Fellowship in Basic Biomedical Research from The Foundation for AIDS Research
Gray’s professional activities aren’t limited to research. He often talks to the press, and in 2010, he joined the Early-Mid Career Researcher Committee at the Alfred Medical Research and Education Precinct, which includes Monash University, the Burnet Institute, and the Baker institute. One of the goals of the committee, which he has chaired since 2012, is to offer better career support to Ph.D. students and postdocs. Over the years, the committee has set up a mentoring scheme; seminars teaching statistics, leadership, and writing skills; a 2-day retreat to promote career and professional development and networking; and collaborative seed grants for young scientists within the precinct. For postdocs, especially, “it’s a critical stage,” he says. They need to develop their skill sets in order to become a lab heads, “but there’s not that much support there for them.”
Gorry and Melissa Churchill—Churchill co-supervised Gray’s Ph.D. thesis and heads his new postdoctoral lab, the HIV Neuropathogenesis Laboratory at the Burnet Institute—both believe that Gray has what it takes to succeed in academia. Yet Gray has never considered academia his only option. “I’m still of two minds, whether I stay within basic science or … move sideways into industry,” he says.
Part of that indecision is probably his self-doubt kicking in again. Even though his research field gives him an edge, funding has become so competitive that “it’s really only going to be the excellent, exceptional people which will continue and stay in the long term,” he says, adding that he sees himself as good but not exceptional. But the main reason for his hesitation is academia’s poor job security. “Because you are grants-based, you’re constantly applying for new funds, and when you’re the major bread winner in the family, it’s tough,” says Gray, now father to a 3-year-old and 1-year-old. Gray enjoys his science and the flexibility it offers, he says, but “family to me is probably the most important.”
Gray “would make an exceptional academic,” Churchill writes. But “I honestly believe with his attitude and skill level, [he] would succeed in any field he decided to move into.”