A career in academia comes with the understanding that one’s literal path in life will be somewhat defined by Following the Work.
Embarking on one such significant change of scenery, Jaya Rajaiya, PhD, associate professor in The University of New Mexico Department of Molecular Genetics & Microbiology, moved to Albuquerque last September from Boston, when her spouse was hired as chair of UNM’s Department of Ophthalmology & Visual Sciences.
While spousal hires are not uncommon, what Rajaiya brought with her is a unique and powerful addition to the research being conducted at UNM: her own third-cycle RO1 grant through the National Institutes of Health (NIH).
“My work focuses on viral entry and trafficking. We specifically work on viruses that cause conjunctivitis, commonly known as pink eye,” Rajaiya says.
“Caused by adenoviruses, they are non-enveloped DNA viruses that we use to study basic cell biology processes. Adenoviruses are famous, in the sense that they taught us a lot about human biology – splicing, cancer studies – a lot of information came through the study of adenoviruses.”
Rajaiya previously worked at the Massachusetts Eye and Ear Infirmary (affiliated with Harvard Medical School), and her grant comes from the National Eye Institute branch of the NIH. Her lab focuses on how adenoviruses enter the cell and hijack normal cellular mechanisms to propagate and produce more viruses. Her research is not translational, which is to say the focus is not on how to cure conjunctivitis, in part because the condition is "self-limiting."
“If you get pink eye, you might be uncomfortable for the first few days or so, but eventually it goes away," Rajaiya says. "It’s not a life-threatening disease. But it is an excellent system to understand how our cells function.”
Once we know how immune cells come into the eye in response to the virus, we can then use inhibitors to block these immune cells trafficking into the cornea, and possibly prevent blurred vision.
Rajaiya’s lab utilizes donor corneas that aren’t suitable for transplants, from people who elect to donate their organs to science. Rajaiya and her fellow scientists grow cells from the corneal tissue and then infect them with the virus and study the cell biology. This is done through a process known as a three-dimensional culture – a “cornea in a test tube”.
“Because corneas are made up of several cell layers, to understand how the infection functions we study all three layers of corneal tissue to see how the entire system of the eye is impacted,” Rajaiya says.
This method of “building” a cornea is somewhat unique. Most corneal research uses a monolayer (single layer) approach to conduct experiments, but Rajaiya and her team want to really understand the full picture. One researcher went so far as to introduce nerve cells into their work, in order to recreate the most accurate corneal facsimile.
When it comes to the function of this research, Rajaiya points out that basic science is what leads to translational science. This is her third RO1 grant cycle, having renewed the grant twice to continue with deeper dives into the work.
“The three-dimensional culture is a very versatile system,” Rajaiya says, “so once we know how immune cells come into the eye in response to the virus, we can then use inhibitors to block these immune cells trafficking into the cornea, and possibly prevent blurred vision.”
Within the scientific community, part of the traditional dogma of virus entry is that there are specific pathways that have previously been identified by other researchers – and those foundations persist used today. Rajaiya’s approach has always been to break away from the confines of dogmas that don’t add up or make sense.
“Traditionally, scientists work with cell lines,” Rajaiya says. “(Most people) have probably heard about the HeLa cell line, which became very famous because it was taken from a patient (Henrietta Lacks) without permission, who was then never given the credit – and it’s the cell line that the whole world uses.
“These cell lines are immortalized, and they are not primary cells. They are not typically the cells that the virus infects. So, when I started my work, I wanted to try and find out: why and how does specific viral entry occur? These are viruses that infect the eye, so they enter through a very specific pathway only in the cells of the eye.”
The pathways are important because how a virus enters the cells also dictates the downstream events, which then leads to cellular responses like the inflammation process. If you start with a standard cell line that isn’t what the virus typically infects, you get a completely different pathway, which can distort your treatment plan.
Rajaiya had to fight to break the constraints of previous studies, which used cell lines that didn’t employ her desired level of specificity, to show that it’s a virus- and-cell-specific process. Moving further down this line of focused study could help lead to finding targeted therapies (for example, treating an infection in your eye vs. one in your knee).
This unique approach may be part of what helped Rajaiya’s work stand out in order to secure funding. NIH grants award a significant amount of money – typically $250,000 per year for three to five years per cycle, along with an additional institutional percentage. Only around 20 percent of grants submitted to the NIH receive funding – a data point that Rajaiya says is a little skewed because every grant gets two submission opportunities.
“So, I can submit my grant and if I don’t receive funding the first time, I have another chance to submit it again,” she says. “Which means the numbers are actually fewer than 20 percent – possibly as low as 10 to 12 percent.”
Rajaiya initially got funding for her grant on her second submission, and also had to submit it a second time to renew funding. It wasn’t until the third grant cycle that she received funding on the first try. To that end, she wants to remind younger researchers to not be discouraged – that the process is highly competitive and can take some time.
“It used to be that by age 35 or 40 people were able to get their first grant, but that average has moved up to 45,” Rajaiya says. “So you’re OK if you get your first grant at 45.”
Despite the daunting statistics, Rajaiya emphasizes that there’s a lot to feel good about in terms of parity.
“NIH grant funding is still very competitive and hard to get, but the distribution of funding is now equal between women and men,” Rajaiya says. “I was very excited to see that part of the data.”