On Dec. 13, 2023, In a study of historic scale, scientists at Gladstone Institutes announced that they had created an intricate map of how the immune system functions, examining the molecular structures governing human T cells using the next-generation CRISPR tool known as base editing.

Led by Gladstone Senior Investigator Alex Marson, MD, PhD, the team dove deep into the DNA of T cells, pinpointing specific nucleotides—the basic units of genetic information in DNA—that influence how immune cells respond to stimuli. In all, they scrutinized more than 100,000 sites across nearly 400 genes found in functioning human T cells.

Nucleotides serve as the basic code for constructing proteins in cells, so by identifying these specific units of DNA, the scientists now have clarity into exact locations within proteins that tune immune responses critical for health. The results serve as a bullseye, marking sites that can be targeted with future immune-modulating drugs.

With immense pools of data generated from the more-than-100,000 sites on T cells, computational genomics became a critical piece of the study. Carl Ward, PhD, a Gladstone postdoctoral researcher and co-first author, led the team’s efforts in this area, keying in on important measures of cell function to create what he hopes can serve as an indispensable resource for immunologists and drug developers alike.

Their findings, published in Nature, uncover detailed information that could help overcome the limitations of today’s immunotherapies and identify new drug targets for a wide range of conditions, including autoimmune diseases and cancer.