Researchers at the University of California San Diego School of Medicine have been awarded nearly $9 million in grants to fund two research projects that will examine the cellular causes of Type 1 diabetes.
The researchers hope to use human pluripotent stem cells, CRISPR and human organoids to dissect beta-cell defects and create a human cell model of Type 1 diabetes.
In doing so, they hope to identify the elusive cellular actions that lead to disease onset.
“We are using technology that, for the first time, allows us to create human conditions that mimic Type 1 diabetes in a culture dish in order to understand the mechanism or genes by which beta cells are killed,” said Dr. Maike Sander, professor in the departments of Pediatrics and Cellular and Molecular Medicine at UC San Diego School of Medicine and co-principal investigator on both grants.
“Our hope is that we can generate the information we need to eventually make beta cells survive in people living with Type 1 diabetes,” he added.
The two multi-year special statutory grants from the National Institute of Diabetes and Digestive and Kidney Diseases are part of the National Institutes of Health (NIH).
Type 1 diabetes is an autoimmune disease that destroys pancreatic beta cells and affects more than 1 million people in the United States.
Pancreatic beta cells, found in groups called islets of Langerhans, help maintain normal blood glucose levels by producing the hormone insulin — the master regulator of energy (glucose). Impairment and the loss of beta cells reduce insulin production, leading to Types 1 and 2 diabetes.
Sanders and Dr. Kyle Gaulton will first try to decipher the function of genes associated with genetic risk for Type 1 diabetes using a high-resolution reference map of pancreatic cells.
After identifying genes associated with beta-cell function, the team, including Dr. Prashant Mali, Dr. Wenxian Fu, and Dr. Graham McVicker, will use CRISPR to validate which genes are promoting cell survival and which are causing cell death.
This information can then be tested using an islet-on-a-chip (human organoid) being developed with the second part of the NIH grant to study the immune attack on beta cells in the dish. Human organoids are miniaturized, 3D versions of an organ.
“We will activate and deactivate genes we think are involved in whether beta cells live or die. We want to know what causes the attack on beta cells because no one has been able to identify it,” said Sander, who is also director of the Pediatric Diabetes Research Center, co-director of the Center on Diabetes in the Institute of Engineering in Medicine and a member of the Sanford Stem Cell Clinical Center.
“We recognize that people who are living with Type 1 may still have beta cells. If we can rescue those cells we may be able to help with blood glucose management and provide a clinical improvement.”
- U.C. San Diego News Center. (2019, August 16). UC San Diego Receives $9 Million in Grants to Pinpoint Cellular Cause of Type 1 Diabetes. Retrieved August 16, 2019, from https://ucsdnews.ucsd.edu/pressrelease/uc-san-diego-receives-9-million-in-grants-to-pinpoint-cellular-cause-of-type-1-diabetes