Immunogenetic regulation of progression to Type 1 diabetes
Dr Anna Long will draw on existing research and expertise from the Benaroya Institute in Seattle and from the University of Bristol to clarify the complex immune pathways that control the rate at which people develop Type 1 diabetes.
Background to research
Type 1 diabetes occurs when the immune system attacks insulin-producing cells in the islets of the pancreas. Slowing this attack to delay or prevent the onset of Type 1 diabetes could have significant benefits for those at risk, but recent clinical trials in this area have met with limited success. Greater knowledge of the immune pathways and signals that alter the rate at which diabetes develops could lead to more effective immune therapies. The Benaroya Institute in Seattle is a world leader in translating laboratory studies of the immune system into the clinic. Scientists there have recently uncovered important differences in the immune system regulation of people with immune markers of Type 1, when compared to those without them. At the same time, researchers at the University of Bristol have identified unique individuals who, despite having close relatives with Type 1 diabetes and multiple immune markers of the condition for more than ten years, have not developed it themselves. These ‘slow progressors’ are thought to be protected by increased activity among a particular kind of white blood cells, known as T-regulatory cells.
A joint Fulbright Diabetes UK Research Award and Moffat Travelling Fellowship (supported by a £90,000 donation from the Moffat Charitable Trust), will enable Dr Anna Long from the University of Bristol to spend two years at the Benaroya Research Institute in Seattle. There she will learn state-of-the-art techniques for measuring T cell function and the activity of immune signalling pathways. Using these techniques she will build on the Institute’s existing work by studying T cell activity in close relatives of people with Type 1 who have multiple immune markers of the condition, and comparing this to T cell activity in relatives without such markers. She will also study the T-regulatory cells in these individuals and explore the mechanisms by which they control the immune cells that kill islets in the pancreas. After two years, Dr Long will return to Bristol and apply what she has learned to measure T cell activity in people identified as ‘slow progressors’ to Type 1 diabetes and compare it with that in people who progress to Type 1 rapidly. She will also study the genes of people from each group to see if different genes are active in these two types of individual. Finally, Dr Long will draw on all of the knowledge she has gained to build a model that will clarify the immune pathways controlling the rate at which people develop Type 1 diabetes.
Potential benefit to people with diabetes
By identifying components of the immune system that delay the onset of Type 1 diabetes, this Fellowship will help us to understand why some people develop Type 1 diabetes in childhood, while others remain free from diabetes for decades, even though they have multiple markers of an immune attack on their insulin-producing islet cells. This knowledge will inform the development of new strategies to help scientists control the immune system and thereby delay or even prevent Type 1 diabetes in those at risk.