Seattle BioMed, a U.S. independent nonprofit focused solely on infectious disease research, has been awarded a grant from the National Institute of Allergy and Infectious Diseases, part of the NIH, which will take a comprehensive systems approach to tuberculosis (TB) infection, harnessing the power of technology and systems biology to examine the progression from latent infection to disease. The grant will total up to $16.6 million over a five-year period.

One third of the world's population latently carries the bacterium that causes TB, and 8.7 million new cases of TB are diagnosed each year. The research will be focused on predicting which carriers will become actively ill with TB.

"Research in TB has never been more critical, and this collaboration represents an important change in how disease research is done, making a move from a ‘trial and error' approach to predictive modeling," said Alan Aderem, Ph.D., president of Seattle BioMed. "By drawing on our collective expertise, and by taking advantage of the predictive power of systems biology, we can tackle the problem of TB in an entirely new way, potentially elucidating new drug targets or informing vaccine development."

The grant integrates the experience of several scientists at Seattle BioMed, in collaboration with the Institute for Systems Biology (ISB) and ETH Zurich. The team comprises researchers from both the host side of the disease and the pathogen side, along with researchers in systems biology and biotechnology.

TB's transition from a latent infection to active disease is a complex process involving nuanced interactions between the bacterium that causes disease and the human immune system. The grant, titled "Omics of TB Disease Progression," will for the first time allow researchers to study many sides of TB infection simultaneously, uncovering the mysteries of how and in whom TB causes illness.

"We hope to identify genes in both humans and bugs that work together to cause disease," said David Sherman, Ph.D., Co-Principal Investigator (Co-PI) of the program and Co-PI of the Pathogen Project. "It will give us the first comprehensive picture of how TB, a notoriously elusive pathogen, progresses to disease."

Globally, someone develops active TB disease every four seconds, and someone dies from TB every 20 seconds. Drug resistance is an enormous challenge in treatment, with 3.7% of new cases and 20% of previously treated cases resistant to at least one course of drug treatment. Totally drug resistant TB has also emerged in several countries. Additionally, HIV facilitates the latent-to-active transmissions of TB because it weakens the immune system. Although TB is the second-leading infectious disease killer worldwide, and the biggest disease killer of HIV-positive people, it receives far less research funding than either HIV/AIDS or malaria.