of type 1 diabetes--one of the most common chron- ic childhood diseases, which results from an auto- 1990, the Insulin-Dependent Diabetes Mellitus Sardinia Project has been investigating preclinical phases of type 1 diabetes in a large cohort of people. The goal is to learn why some people who are genetically at risk for type 1 dia- betes don't develop the disease. data mining for this and other projects because of its isolat- ed population. It's simpler to investigate the environmental, is linked to genes in the major histocompatibili- ty complex (MHC) called human leukocyte anti- regulate the immune system. "There are HLA class I and class II genes, and the class II genes have a stronger link to autoimmunity," she adds. Although 50 percent of genetic components are linked to HLA molecules, other genes in the MHC are also involved. "Because HLAs occur in so many different forms, the diversity makes them difficult to study in terms of autoimmune disease," says Dr. Denzin. The Sardinian team was interested in knowing if not only HLA class II genes but also other genes encoded within the type 1 diabetes. that Dr. Denzin's laboratory works on--called DM--is associated with protection from type 1 diabetes. DM con- trols the presentation of HLA class II proteins at the cell surface--known to trigger immunity. Finding a specific allele of DM that is mediating protection from type 1 dia- betes suggests that this allele--or version of DM--might in fact alter this process, thereby leading to protection. Francesco Cucca, MD, professor of medical genet- ics, University of Sassari, Italy, and director of the Biomedical Research, and Valeria Orrú, PhD, permanent researcher, University of Cagliari, Italy. "We received an email from Dr. Orrú expressing an interest in our mouse model results--where we showed if we altered activity of the DM protein, we could protect a non-obese diabetic mouse from diabetes," says Dr. Denzin. "They suggested to us that modulating DM activity could be the mechanism by which the people in the Sardinian study are protected from type I diabetes." dent of Dr. Orrú's, became part of the project, working in Dr. Denzin's lab as a postdoctoral research fellow. Dr. Virdis's goal is to use biochemical and cell biological assays established in Dr. Denzin's lab to answer the question of altered activity. "If we can show that this DM has altered function, we could make a significant discovery in type 1 diabetes," says Dr. Denzin. Target for Type 1 Diabetes tion, so you can't simply get rid of them. What's important about this idea is that rather than try- function," says Dr. Denzin. "DM could be a druggable target. Potentially changing the way the molecule works might be enough." A protective genetic variant could lead to a useful treatment. "Usually people are looking for lots O E M R S O |