TSRI Study Points Way to Better Vaccines and New Autoimmune Therapies
A new international collaboration involving scientists at The Scripps Research Institute (TSRI) opens a door to influencing the immune system, which would be useful to boost the effectiveness of vaccines or to counter autoimmune diseases such as lupus and rheumatoid arthritis.
The research, published August 1, 2016, in The Journal of Experimental Medicine, focused on a molecule called microRNA-155 (miR-155), a key player in the immune system’s production of disease-fighting antibodies.
“It’s very exciting to see exactly how this molecule works in the body,” said TSRI Associate Professor Changchun Xiao, who co-led the study with Professor Wen-Hsien Liu of Xiamen University in Fuijan province, China.
An Immune System Tango
Our cells rely on molecules called microRNAs (miRNAs) as a sort of “dimmer switches” to carefully regulate protein levels and combat disease.
“People know miRNAs are involved in immune response, but they don’t know which miRNAs and how exactly,” explained TSRI Research Associate Zhe Huang, study co-first author with Liu and Seung Goo Kang of TSRI and Kangwon National University.
In the new study, the researchers focused on the roles of miRNAs during the critical period when the immune system first detects “invaders” such as viruses or bacteria. At this time, cells called T follicular helpers proliferate and migrate to a different area of the lymph organs to interact with B cells.
“They do a sort of tango,” said Xiao.
This interaction prompts B cells to mature and produce effective antibodies, eventually offering long-term protection against infection.
“The next time you encounter that virus, for example, the body can respond quickly,” said Xiao.
Identifying a Dancer
Using a technique called deep sequencing, the team identified miR-155 as a potential part of this process. Studies in mouse models suggested that miR-155 works by repressing a protein called Peli1. This leaves a molecule called c-Rel free to jump in and promote normal T cell proliferation.
This finding could help scientists improve current vaccines. While vaccines are life-saving, some vaccines wear off after a decade or only cover around 80 percent of those vaccinated.
“If you could increase T cell proliferation using a molecule that mimics miR-155, maybe you could boost that to 90 to 95 percent,” said Xiao. He also sees potential for using miR-155 to help in creating longer-lasting vaccines.
The research may also apply to treating autoimmune diseases, which occur when antibodies mistakenly attack the body’s own tissues. Xiao and his colleagues think an mRNA inhibitor could dial back miR-155’s response when T cell proliferation and antibody production is in overdrive.
For the next stage of this research, Xiao plans to collaborate with scientists on the Florida campus of TSRI to test possible miRNA inhibitors against autoimmune disease.
Researchers uncover molecular switch to make effective sugar-responsive, insulin-releasing cells in a dish, offering hope for diabetes therapy
Salk scientists have solved a longstanding problem in the effort to create replacement cells for diabetic patients. The team uncovered a hidden energy switch that, when flipped, powers up pancreatic cells to respond to glucose, a step that eluded previous research. The result is the production of hundreds of millions of lab-produced human beta cells—able to relieve diabetes in mice.
For more than a decade, scientists across the globe strived to replace failing pancreatic beta cells linked to immune destruction in children (type 1 diabetes) or obesity-associated diabetes in adults (type 2 diabetes). Although cells made in a dish were able to produce insulin, they were sluggish or simply unable to respond to glucose.
“We found the missing energy switch needed to produce robust and functional human beta cells, potentially turning this discovery into a viable treatment for human diabetes,” says Ronald Evans, co-senior author and director of the Gene Expression Laboratory at Salk. The new work was published in Cell Metabolism on April 12, 2016.
The Salk Institute for Biological Studies is an independent, non-profit, scientific research institute located in La Jolla, California.
It was founded in 1960 by Jonas Salk, the developer of the polio vaccine; among the founding consultants were Jacob Bronowski and Francis Crick. Building did not start until spring of 1962. The institute consistently ranks among the top institutions in the US in terms of research output and quality in the life sciences. In 2004, the Times Higher Education Supplement ranked Salk as the world’s top biomedicine research institute, and in 2009 it was ranked number one globally by ScienceWatch in the neuroscience and behavior areas.
The institute employs 850 researchers in 60 research groups and focuses its research in three areas: Molecular Biology and Genetics; Neurosciences; and Plant Biology. Research topics include cancer, diabetes, birth defects, Alzheimer’s disease, Parkinson’s disease, AIDS, and the neurobiology of American Sign Language. The March of Dimes provided the initial funding and continues to support the institute. Current research is funded by a variety of organizations, such as the NIH, the HHMI and private organizations such as Paris-based Ipsen and the Waitt Family Foundation. In addition, the internally administered Innovation Grants Program encourages cutting-edge high-risk research. The institute appointed genome biologist Eric Lander and stem cell biologist Irving Weissman as non-resident fellows in November 2009.
The campus was designed by Louis Kahn. Salk had sought to make a beautiful campus in order to draw the best researchers in the world. Salk and Kahn having both descended from Russian Jewish parents that had immigrated to the United States had a deeper connection than just mere partners on an architectural project. The results of their connection is seen in the design that resulted from their collaboration. The original buildings of the Salk Institute were designated as a historical landmark in 1991. The entire 27-acre (11 ha) site was deemed eligible by the California Historical Resources Commission in 2006 for listing on the National Register of Historic Places.
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- One injection stops diabetes in its tracks – July 17, 2014
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