Researchers at UT Southwestern are advancing towards a comprehensive layout of the mammalian immune system.
In a significant leap forward in immunology research, a team led by Nobel Prize winner Bruce Beutler has identified 101 novel gene candidates with a high probability of being essential for immunity. The study, which is part of an ongoing research program aimed at identifying every mutation that may affect the mouse immune system, was published in the Proceedings of the National Academy of Sciences.
The research, conducted at the Center for the Genetics of Host Defense (CGHD) at UT Southwestern, used a software called Candidate Explorer (CE). This machine-learning algorithm analysed about 87,000 mutation/trait associations, ultimately identifying 2,336 mutations in 1,279 genes as good or excellent candidates for causation of traits related to immunity.
The CE software determines the probability that any mutation will be verified as causative after further testing. Over time, the program "learns" from experiments in which researchers re-create the mutation in a fresh pedigree and verify or exclude the hypothesis of causation.
Beutler, who is also the Regental Professor, professor of immunology and internal medicine at UT Southwestern, won the 2011 Nobel Prize in Physiology or Medicine for his discovery of an important family of receptors that allow mammals to quickly sense infection and trigger an inflammatory response. He holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr.
The study focused on changes in cells known to be tied to immunity, such as B cells, T cells, macrophages, and natural killer cells. Notably, the mouse and human genome are very similar in size and content of genes, with almost all mouse genes having a human counterpart, and vice versa.
The identified gene mutations were made available to the scientific community through a public repository, and the data supporting causation are viewable within the Candidate Explorer program on the CGHD website, Mutagenetix. UTSW co-authors include several researchers from various departments, and collaborators from Japan and China also contributed to the study.
However, the project led by researcher Rajewsky, who is working on genetic repair of T-cells in mouse models, faces funding difficulties for clinical trials due to the rarity of these diseases in humans. The exact support from the National Institutes of Health (NIH) for this project could not be confirmed from the available information.
The work received support from the National Institutes of Health (grants R01 AI125581 and U19 AI100627). The research team's ongoing efforts promise to continue unravelling the complexities of the immune system, potentially leading to breakthroughs in understanding and treating immune-related diseases.
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