Tuberculosis (TB) remains one of the world’s deadliest infectious killers, spread through inhaling tiny droplets from the cough or sneeze of an infected person.

According to the World Health Organization’s global TB report 2021, the COVID-19 pandemic caused an increase in TB deaths—1.5 million in 2020 vs. 1.4 million in 2019—due to a lack of efficient diagnosis and treatment.

While TB is a serious contagious disease, it’s both preventable and curable with proper treatment. However, the search for a highly effective vaccine for tuberculosis—the world’s leading cause of death from an infectious agent—has been somewhat elusive. 

But researchers are making headway as they turn to high-performance computing (HPC) to better understand the disease.

HPC shines a light on elusive immune cells.

Published in Frontiers of Immunology, research led by Professor Denise Kirschner from the University of Michigan (UM) Medical School shed much-needed light on a particular group of cells called neutrophils. 

Neutrophils, produced in the bone marrow, are naturally-occurring immune cells responsible for killing off Mycobacterium tuberculosis—a species of pathogenic bacteria that causes TB—when they are detected in the body.

Studying the behaviour of neutrophils can help researchers design better drugs and treatments to treat TB. But this process has historically been tricky, as neutrophils are unstable cells with short life spans when grown in the lab.

Now, with access to supercomputers, UM researchers can carry out predictive simulations which allow them to peek into the cells of TB granulomas. Granulomas are the pathological hallmarks of TB—dense, spherical collections of immune cells that serve to protect the host by isolating bacteria, which also simultaneously provide a place for bacterial survival and growth. With this newfound ability to open a window into the cells, the researchers can create high-resolution models illustrating how neutrophils react when a host is infected with TB.

Forging a path to better TB vaccines.

As the immune system is made of many cells working together to fight off microbial invaders, being able to closely image these cells in the granuloma allowed the researchers to inform their model.

The simulations revealed the dual role of neutrophils—spreading and containing the infection. With new knowledge on both mechanisms and information regarding the role of neutrophils in the immune response to TB, the computational models could show how the host process contributes to immune and drug dynamics—from the molecular level to the entire host.

While there is a vaccine for TB (BCG vaccine—not widely used due to its variable efficacy), and a few others in trial, this computational approach will help narrow the “vaccine design space”. Developing and testing the models, and using them to make critical predictions about TB treatment and prevention will bring researchers much closer to a globally effective TB vaccine.

HPC is increasingly important in biological studies.

This work would’t have been possible on a desktop computer. The researchers ran their complex code on the Expanse supercomputer at the San Diego Supercomputer Center, where thousands of runs of a sequential simulation model were needed to produce results. Check out the technical details of the HPC system here.

As big data permeates the realm of life sciences, we are witnessing an unprecedented growth of HPC demand in the field. For instance, studying the human brain, which contains over 86 billion neurons, requires advanced computational and storage technologies to effectively decode and ascertain the mechanisms responsible for brain function at a cellular level. Imaging an entire brain at cellular resolutions produces petabytes of data. The electron microscopy of a brain would amount to more than one exabyte of data!

From genomics and vaccine development to neuroscience and bioinformatics, HPC is becoming an increasingly crucial tool in the quest to formulate better treatments, develop effective disease prevention and advance human health. The ability to solve challenges in these areas will rest on the cooperation and collaboration of many different industries and research disciplines.

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