Krishna Roskin, PhD, a new informaticist and immunobiologist at Cincinnati Children’s, is pairing computational methods with immunobiology to improve our understanding of the human immune system.
One of his big ideas is to aggregate immune system data into an atlas to serve as a reference. “The number of distinct antibodies, while large, is finite, and therefore tabulable,” he says. “If we could create an antibody dictionary that associates antibodies with their antigens, we would be able to analyze the blood sample of a person with an unknown infection to make a diagnosis or look for signs of past antigen exposure. Such a dictionary would also be useful in reverse engineering vaccines.”
“I want to be a bridge between immunology and informatics,” he says. In his newly established lab, he is excited about applying emerging analytical and computational techniques to the study of immunological samples from humans.
“My background is in computational biology. I want to diversify that view,” says Roskin. “My hope is that clinicians will help keep me grounded in my research. To me, it’s data. To them, it’s patients. ‘That’s a real person. I saw them in the clinic last week.’ When clinicians mention that, it’s a reminder for me: they actually see these patients and care for them. They are real people, not just data.”
Mouse genome and human immunity
Roskin picked a good time and place to enter the field of genomic research. He began his studies at the University of California Santa Cruz when the first draft of the human genome was completed and mammalian comparative genomics, in the form of the Mouse and Rat Genome Projects, was being born.
At that time, Roskin’s work centered on analyzing the mouse genome and comparing it to the human genome. The results distinguished functional regions of the human genome that help us better understand disease susceptibility and provided an estimate of the fraction of the human genome that was under selection. These results were later refined with the addition of the rat genome. Studies on these topics are still active to this day.
Along the way, Roskin became particularly interested in the immunoglobin and T cell receptor loci that play a central role in our adaptive immune system. He wondered what we could learn about immune diseases from the way antibody genes mutate or were selected. To find some answers, Roskin joined the laboratory of Dr. Scott Boyd at Stanford University, where he used computational sequence analysis to better understand the range of human immune responses.
Wet lab and single-cell sequencing
He is now applying the computational skills and insights he gained from full genome comparative analysis to sequence-based immune monitoring.
Emerging sequencing technologies are moving this area forward rapidly. “I’m applying that to cells of the immune system. Every antibody producing cell can have its own genome,” says Roskin. “There’s a lot of interest in single-cell sequencing and expression. If we want to start creating drugs or testing for specific characteristics, single-cell sequencing will help us identify antibodies of interest.”
Some of these questions couldn’t be answered by studying immunity in animal models. So, to get those all-important human samples, Roskin is establishing a wet lab—meaning one that is equipped to handle and process biological samples—a somewhat unusual capability for an informaticist. “My goal is to be an attractive collaborator,” says Roskin. “Having a wet lab makes it much easier to connect with someone who has interesting samples—they can just provide me the samples, and my lab can handle the processing and data generation. There will be a lot more possibilities to collaborate with people who don’t have time to do all the processing steps themselves.”
Immune memory and bone marrow
Blood is the most commonly used human sample, and for good reason—it’s easy to get. But new studies suggest that blood samples may be leaving out important clues about human immunology.
“Blood circulates, samples, and tastes a lot of what’s going on in the body,” says Roskin. “But if you want to look at immune memory, that information might be hidden in other tissues. Immune memory cells do circulate, but in much smaller numbers that can be difficult to detect. It’s hard to pick out one scout in a whole army. That cell could be hiding out in the bone marrow and be much easier to find there.”
Bone marrow samples may not be easy to come by, but Roskin hopes that his lab will attract clinicians with access to samples. In the wet lab, Roskin and his team will have the necessary tools in place to study a wide variety of both animal and human samples. The more samples they can study, the more they can uncover about the human immune system.
Immunology is about understanding the interactions that cause a certain response. With the collaboration between informaticists, immunologists, and clinicians in Krishna Roskin’s lab, he hopes to get a different kind of interaction— “Good synergies,” he says.