Son’s health issues fuel UNL researcher’s interest in building virtual immune system | Health and fitness
For decades, engineers have used computer models to simulate engine and rocket operation before launch, and today’s passenger aircraft engines have computer replicas that alert airlines when repairs are needed. required.
A researcher at the University of Nebraska-Lincoln is working to develop a similar tool for one of the most complex machines in the human body – the immune system.
Tomáš Helikar, associate professor of biochemistry at UNL, said having a computer replica of the immune system could help researchers better understand and even personalize the treatment of immune system-related diseases and increase the speed and the efficiency of drug development.
Helikar and his team have already developed a model based on one type of immune cell – the CD4+ T cell, the so-called helpers that stimulate other cells to fight off pathogens.
His next goal: to extend the model to cover the entire immune system. It’s a tough challenge, but Helikar has a powerful motivation. Her son, Liam, now 7½, was born in 2014 with a genetic condition that prevented his lungs from working. Liam underwent a double lung transplant when he was 9 weeks old.
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The lung transplant solved the problem, but the drugs Liam takes to prevent his body from attacking his lungs compromised his immune system.
Helikar, from the Czech Republic, said Liam is a passionate, loving and happy child who is bilingual and loves skiing. He started first year in the Czech Republic while Helikar was on sabbatical there for the last six months of 2021. He now attends school in Lincoln.
“He does all kinds of things that other kids do that wouldn’t have been possible without the lung transplant,” Helikar said. “But of course there were many challenges along the way due to immunosuppression.”
In fact, Liam contracted COVID-19 in the Czech Republic in December and was hospitalized there. He required aggressive treatment.
“It fuels my interest in the immune system,” Helikar said. “I think the immune system can be understood as a system, and it can be changed and reprogrammed more strategically to achieve a healthy state.”
The pandemic has opened many eyes to the importance of the immune system, he said. Although scientists know what each type of cell in the system does, it is difficult to predict how this system will behave when these cells begin to interact.
Liam’s drugs, for example, suppress CD4+ T cells, Helikar said. But because these cells are part of a complex network, deleting them has the potential to affect other immune cells in ways that can impact the body and health.
No two people have the same immune system, he said. Everyone is conditioned differently by exposure to different diseases and environmental factors. As a result, each person’s immune system reacts differently to pathogens.
The UNL researchers tested their model’s ability to predict cell behavior in response to influenza infection, and the results were published in August in PLOS Computational Biology. Since then, they’ve used a similar model to identify candidate flu drugs, and they’re now testing them.
“We are seeing very good results,” Helikar said. “We have two drugs that, when given together, really inhibit virus replication.”
Although the researchers haven’t tested the drugs against other viruses, they think they might work on other viral infections.
Currently, the process of moving a new drug candidate through the development pipeline takes about a decade and costs, on average, between $1.2 billion and $2.5 billion, Helikar said. And many failures occur along the way, with only a 7% chance of any given drug making it to phase 1 human clinical trials.
“These very poor odds for drug development are what makes drug development so expensive and why it takes so long,” he said.
Helikar’s team plans to expand the model to include more types of cells, molecules, genes and organs and the mechanisms they use to communicate with each other.
It’s a big challenge. The original single CD4+ T cell model incorporated four different modeling approaches to integrate three-level processes in different tissues.
“We go from the molecular level to the cellular level to the whole body level,” Helikar said. “And computationally and mathematically, that’s a very difficult task to accomplish.”
A five-year, $1.8 million grant from the National Institutes of Health Maximizing Investigators Fellowship Program will help the team take some of the next steps. An earlier grant of $1.77 million under the program funded the initial work. The team now has 15 members who have expertise in areas such as software development, computational biology and immunology.
Among its next steps, Helikar envisions enabling the model to account for the physiology of an individual or demographic group, a step that could open the door to personalized medicine.
Helikar is not alone in seeking to create models of the immune system. He is also part of a task force, formed at the request of the NIH at the start of the pandemic, which proposed the development of an immune digital twin for use in viral infections such as COVID.
James Glazier, one of the group’s two organizers and a professor in Indiana University’s Department of Intelligent Systems Engineering, said the group was formed because little modeling work was being done to understand what happened once a person was infected with the virus. Most of the modeling available instead focuses on pandemic epidemiology, trying to understand things like the number of people infected and the effects of masking and distancing.
Reinhard Laubenbacher, the group’s other organizer and professor of systems medicine at the University of Florida, said the questions include why a healthy 25-year-old can die of COVID-19 in a short time and an 85-year-old diabetic. survives with the equivalent of a bad cold.
Such a model, Laubenbacher said, could also allow a doctor to determine which drugs will work for a particular COVID patient, simplifying hospital operations and potentially saving lives.
Says Glazier, “What we need to do now is predict the immune status within an individual rather than in a population.”
Computational models currently available in healthcare allow doctors to determine if blockages are affecting blood flow through cardiac vessels and simulate the effects of interventions such as surgery on these flows. They also power the latest insulin pumps, which monitor the blood sugar levels of diabetics in real time.
But the researchers want to push the models further. Glazier said Helikar’s work on T-cell modeling “is exactly the type of combined modeling and experimentation work that we believe is essential to advancing the understanding of the human immune response.”
Helikar is also partnering with doctors at the University of Nebraska Medical Center to explore how his model can help transplant recipients. And he’s part of a National Institute for Strategic Research team doing Department of Defense work to develop drugs to protect military personnel from the effects of radiation exposure.
These two collaborations put him on familiar ground. Helikar earned his undergraduate degree at the University of Nebraska in Omaha’s new bioinformatics program and his Ph.D. in biochemistry at UNMC. He completed a post-doctoral program in the Department of Mathematics at the UN.
Helikar has also developed a web-based computer simulation platform called Cell Collective to model biological networks in science research and education.
Glazier, who develops modeling tools focused on solid tissues, said such work encourages collaboration in the field.
“I really admire Tom as someone who combines fantastic science with a real commitment to the community,” he said. “It’s not such a common thing.”