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  • Genome-wide study in fruit flies to identify genetic risk factors for Type 2 diabetes

Research team to conduct genome-wide study in fruit flies to identify genetic risk factors for Type 2 diabetes

Wednesday, August 2, 2023

Fruit fly (Drosophila melanogaster) on banana fruit surface.
Fruit fly (Drosophila melanogaster) on banana. Photo by Arif_Vector, Adobe Stock 449994398

The number of people suffering from diabetes is constantly increasing worldwide, with more than 1 in 10 individuals now living with some form of this disease. Among those nearly 550 million diabetes patients, most of these individuals are assumed to have Type 2 diabetes.

Type 2 diabetes (T2D) is a progressive disease that is caused by defects in the ability of our bodies to produce and/or respond to the hormone insulin. While the negative medical outcomes surrounding T2D have been extensively studied, the mechanisms by which lifestyle, nutrition, and genetic risk factors jointly interact to trigger the onset and early progression of T2D remain poorly understood.

In order to better understand how individual genes contribute to the early stages of T2D, the National Institutes of Health has awarded nearly $3 million to an international research team led by Jason Tennessen, an associate professor in the College of Arts and Sciences’ Department of Biology at Indiana University Bloomington. The goal of this award is to determine how genetic risk factors, gene-by-diet interactions, and disruptions of tissue-specific gene function induce the onset and progression of T2D.

Jason Tennessen.
Jason Tennessen. Photo by James Brosher

The Tennessen lab—in collaboration with the labs of Angelo D’Alessandro (University of Colorado School of Medicine) and Norbert Perrimon (Harvard Medical School), as well as Steven Marygold at FlyBase/University of Cambridge and the Bloomington Drosophila Stock Center (IU Bloomington)—will use this award to conduct a large-scale study of metabolic genes in the fruit fly Drosophila melanogaster. The researchers will use multi-omics to conduct a genome-wide study of metabolic genes in the fruit fly Drosophila melanogaster with the goal of identifying metabolic enzymes and small molecule transporters that contribute to onset and progression of T2D. More simply said, they will seek the conserved genes that protect against a high sugar diet and prevent Type 2 diabetes.

Tennessen and his team chose to conduct this study in D. melanogaster because flies, like humans, are at risk of developing T2D when fed a high sugar diet. Moreover, many of the same hormone signals and metabolic pathways that regulate sugar metabolism in humans are conserved in flies. For example, insulin is the key regulator of blood sugar levels in flies, just as it is in humans. Using recent technological advances that enable the rapid and precise measurement of carbohydrate metabolism and gene expression, the team will disrupt expression of over a thousand individual genes and determine how loss of any single gene affects the onset of T2D in flies fed a high-sugar diet.

This study is only possible due to the collaborative team that includes three of the world’s premier genetic resource centers.

  1. The DRSC Functional Genomics Resources/Transgenetic RNAi Project at Harvard Medical School generated the genetic strains being used in the project.
  2. These lines are maintained by Bloomington Drosophila Stock Center, which is located within the IU Bloomington Department of Biology and houses over 80,000 D. melanogaster strains.
Shelves filled with clear glass vials of live fruit flies. White cotton stoppers close each vial. Vials are grouped in labelled trays. Individual vials are each marked with a white tag.  Yellow, pink, blue, or green index cards with data about the flies stick out from the front of each tray.
The Bloomington Drosophila Stock Center at Indiana University Bloomington maintains a living stock collection of over 80,000 genetically defined strains of D. melanogaster. Photo by Terri Greene
  1. Finally, the data generated by this project will be used to inform metabolic pathway models that will be curated by FlyBase, the official Drosophila knowledgebase that is jointly run by Indiana University Bloomington, Harvard Medical School, and the University of Cambridge.

Upon completion of their research, Tennessen and his collaborators will have generated one of the most comprehensive in vivo metabolic studies ever conducted in animals. Moreover, the results will significantly advance our understanding of how excess sugar consumption rewires the metabolism of individual cell types and identify the metabolic mechanism by which excess sugar consumption contributes to Type 2 diabetes and other metabolic diseases.

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