Nebraska scientist in race to create immune systems
Lincoln, Nebraska, February 7, 2022 – A renewed National Institutes of Health grant will allow a University of Nebraska-Lincoln researcher to continue developing a tool that sheds light on the complex, multi-scale interaction of the many components of the immune system.
Tomas Helikar, Susan J. Rosowski Associate Professor of Biochemistry, will use the five-year, $1.8 million grant from the NIH’s Maximizing Investigators’ Research Award program to advance his work on a virtual immune system aimed at increasing our understanding of immune system diseases and accelerating the speed and efficiency of drug development.
Helikar believes the model could significantly reduce the time and cost of a drug’s journey from lab to market, which often takes more than 10 years and costs about $1.3 billion.
“By being able to map, model and simulate the human immune system, the goal is to identify more effective drug targets and eliminate the wrong assumptions that could lead you down a rabbit hole that leads nowhere. “, said Helikar. .
The model would fill a gap in the science of human health. Although the immune system is arguably one of the most complex “machines” in the human body, there is no computer representation of it that allows scientists to test hypotheses in a low-stakes environment.
“One way to think about it is that we have models of engines and rockets that we simulate before using them, and we are able to predict the different parameters that will make them work,” he said. “On the human health side, we don’t really have that equivalent. Our long-term goal is to develop a tool like this.
It’s a daunting task: the immune system includes organs, tissues, antibodies, cells, genes and more that constantly influence each other’s behavior. These interactions take place at different scales: in different parts of the body, at different points in time and at different levels of organization.
To demonstrate the viability of including each of the scales in a single model, Helikar and a team of Husker collaborators – whose expertise includes software and technology development, immunology, biology, biochemistry and au beyond – used the first installment of the MIRA grant to build computational methods and a tool focused on a single type of immune cell. They selected CD4+ T cells, which are “helpers” of the immune system that stimulate other cells to fight pathogens.
As detailed in a study recently published in PLOS Computational Biology, the team successfully built a model based on CD4+ T cells incorporating four different mathematical approaches, three spatial scales and different immune tissues.
The team’s success in launching this model was critical, Helikar said, because it established a method to mathematically and computationally connect the different scales of the immune system. But expanding the model to include more cell types, molecules, genes and organs will require linking an even larger number of mathematical approaches in a computationally efficient way. Removing this obstacle by improving the speed and efficiency of the model’s algorithms is a major goal for the next five years.
Helikar also plans to allow the model to account for the physiology of an individual person or a particular demographic group. This step can open the door to personalized medicine, where doctors can tailor treatment regimens based on a particular patient’s immune function.
Although the scale of the project is daunting, Helikar is motivated by his experiences as a father. In 2014, his son was born with a rare genetic mutation that required a double lung transplant at the age of nine weeks, making him the second youngest human to have had the procedure.
The transplant has so far given Helikar’s son seven years of life, two years longer than the average life expectancy for lung transplant recipients. But one of the costs of the procedure is a weakened immune system: when a patient undergoes a transplant, their immune system may view the new organ as an invader and attack it.
To dampen this response, transplant recipients take immunosuppressive drugs. But these drugs universally weaken the immune system, making patients more susceptible to infectious diseases and cancer.
The trick, Helikar said, is to fine-tune the immune system so that it doesn’t destroy the transplanted organ, but retains its ability to protect recipients from everything else. Seeing firsthand the need to strike this delicate balance, he nurtured his research ambitions.
“With my son, it allowed me to focus on the immune system,” Helikar said. “I see the importance of fully understanding how the immune system works and how we can actually rewire and reprogram it to do what we need it to.”
With support from the University of Nebraska Collaborative Initiative, Helikar is partnering with physicians at the University of Nebraska Medical Center, including a liver transplant expert, to explore how his model can help recipients of graft.
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