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6 Month Update
Our efforts have yielded promising results in optimizing conditions for the enrichment of IgA+ populations. All the samples have already been sorted and stored at -20°C for further steps. This phase of the project underscores our commitment to methodological refinement and precision in experimental design. For the next six months, I plan to standardize the library preparation process by utilizing different kits to achieve better and more uniform results. Once the standardization is complete, all samples will be used for library preparation for shotgun sequencing. This will include IgA-targeted, non-targeted, and pre-sorted microbes from the controls and T1D samples by August 2024. The bioinformatics analysis will be completed by September 2024. Based on our data, we will select and evaluate species that are more IgA+ targeted in the population in T1D progressors and controls. This will help us decipher the intricate interplay between IgA+ gut commensals and the onset of T1D. This plan not only aims to advance our understanding of IgA+ populations but also sets the stage for potential breakthroughs in understanding the microbial factors influencing T1D progression. We extend our heartfelt gratitude to the Diabetes Research Connection for their unwavering support throughout this project.
Project Description
Type 1 diabetes (T1D) is a condition where the immune system attacks and destroys insulin-producing beta cells, leading to a deficiency in insulin production and elevated blood sugar levels. Genetics alone cannot explain the increased incidence of diabetes worldwide, indicating the role of environmental factors. These factors include viral infections, dietary components, and gut microbiome that are potentially playing a role in disease progression in genetically susceptible individuals.
In this project, I will determine the role of the immune interaction of gut microbes in T1D, focusing on immunoglobulin A (IgA). IgA is a crucial antibody in the immune system that defends our body against pathogens. It is primarily found in mucosal areas such as the gastrointestinal, respiratory, and urogenital tracts, saliva, tears, and breast milk. IgA works by binding to and neutralizing harmful pathogens, protecting the body from infections. Moreover, IgA also shapes the gut microbiome composition by coating beneficial bacteria and preventing them from being attacked by the host immune system. Alterations in IgA have been shown to increase the risk of several autoimmune diseases; however, there is limited data about IgA response in the gut microbiome of T1D patients.
Research showed that IgA levels are higher in T1D patients. However, we don’t know precisely how IgA and the bacteria interact and contribute to the disease. Therefore, the goal of my project is to determine the IgA-coated bacteria in T1D and study their role in disease development. In this study, we obtained stool samples from children at ages 1, 2.5, and 5. We will compare their gut microbiome composition and the targets of the IgA, comparing healthy individuals to children who developed T1D later in life (T1D progressors).
Additionally, we will use a mouse model of T1D to study the role of IgA-coated bacteria on disease onset. The hypothesis is that IgA-coated bacteria play a crucial role in T1D pathophysiology. If we determine a causal link between these gut microbes and T1D onset, it will guide us to develop new therapeutics that specifically target these bacteria to prevent T1D onset in the future. Additionally, beneficial bacterial species can be used for probiotics for the prevention of T1D. I am very excited about this project, and I remain deeply grateful to the DRC and the donors for the support extended to us through this prestigious award and recognition.
