Zaghloul, Norann Amir, PhD
Functional annotation of type 2 diabetes associated loci
General Research Subject: Type 2 Diabetes
Focus: Genetics, Genetics\Type 2 Diabetes, Islet Biology, Islet Biology\Beta Cell Growth and Differentiation, Other
Type of Grant: Innovation
Project Start Date: January 1, 2013
Project End Date: December 31, 2014
Diabetes Type: Type 2 diabetes
Understanding the role of genetics in type 2 diabetes (T2D) is one of the major challenges facing the field of diabetes research. Advances in genome-wide screening technologies have identified genes associated with the disorder, but an understanding of how these genes contribute to disease mechanism has been difficult due to the challenges of assessing gene function in a large scale manner. To address this question, the proposed study will use the zebrafish to systematically investigate the function of each T2D-associated gene in the production of beta cells. These cells are the insulin-producing cells of the body making them critical for control of blood glucose.
Furthermore, T2D patients typically exhibit a loss of these cells making them central to the etiology of disease. It will be important, therefore, to understand how genes that confer susceptibility to the disease contribute to the production and maintenance of beta cells. We propose to achieve this understanding by using a model, zebrafish, that is amenable to large scale functional genetic investigation and a process, beta cell production, that is directly related to disease.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and curing diabetes?
This project investigates the function of genes associated with T2D by studying their role in beta cell development. We are using a transgenic zebrafish line with beta cells specifically labeled for observation in live embryos. By knocking down each gene individually, we will understand how it affects the development of these insulin-producing cells. Our hope is to understand how changes in production of beta cells, either initially during development or later during regeneration in diabetic adults, can contribute to genetic susceptibility to the disease.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
This project will help us understand what it means to be genetically at-risk for T2D. By achieving that understanding, we will learn about the processes that are abnormal in susceptible individuals and target them for intervention.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
My father was diagnosed with T2D over 20 years ago and continues to struggle with the disease. Additionally, nearly all of his siblings are also afflicted with the disease. Having witnessed firsthand how the disease progresses and how it differs between individuals even within the same family, I am very interested in understanding how the genes responsible contribute to the pathology of the disease. This award will allow us to conduct a large scale investigation of all genes associated with T2D and understand their function with respect to disease etiology.
In what direction do you see the future of diabetes research going?
With the tremendous progress in genetics, we are now witnessing the possibility of truly deciphering the complex mechanisms that contribute to diabetes. As we continue to identify disease genes, the challenge that faces us will be how to decipher the roles of each of those genes. I believe we will continue to uncover the fundamental biological disruptions associated with the disease and, with that, better understand the interaction of our inherent biology with environmental influences.
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