Influence of epigenetic modifications in the clinical remission phase (honeymoon period) of adult-onset Type 1 Diabetes

**New Projects On Offer for 2025** Type 1 diabetes (T1D) is an organ-specific autoimmune disease that leads to the destruction of pancreatic islet β cells, resulting in glucose dysregulation and a life-long dependence on exogenous insulin treatment. At diagnosis most individuals with T1D retain some level of functioning β cells, however the rate of β cell loss varies for some and the preservation of these functional β cells is associated with fewer clinical complications. During the disease, some patients experience this phase of Partial Clinical Remission also known as the "honeymoon-period". This is a transitory period that is characterized by insulin production by the remaining β cells following diabetes diagnosis and the initiation of insulin therapy. The regulatory mechanisms of partial clinical remission are poorly understood. The aim of our study is to identify the epigenetic modifications that influence clinical remission. The modification of DNA plays key roles in regulating gene expression in human health and disease. Understanding these modifications and how they contribute to disease and/or predict disease progression is a focus of the Human Epigenetics Laboratory. One of the most widespread genomic modifications is 5-methylcytosine (5mC), which most frequently occurs at CG dinucleotides. Examining this modification on a genome wide scale has typically involved bisulfite conversion or 5mC affinity enrichment methods for detection using common high-throughput sequencing methods. This project will use Nanopore sequencing to distinguish DNA modifications associated with partial clinical remission in T1D. The technology achieves this by-passing nucleotide strands through a protein nanopore that detects unique disruption in voltage / current corresponding to individual bases. Nanopore sequencing also enables detection of other base modifications such as 5hmC with application of specific base-calling algorithms. This project will apply Nanopore sequencing to examine the potential role of DNA methylation in regulation of “honeymoon period” of clinical remission.