Disease is a perturbation of normal biology. A disease model allows us to probe the relationship between the genetic cause, the molecular consequences and physiological symptoms of the disease. Systems such as zebrafish, in addition, are excellently suited for drug discovery screens. In the lab we focus on two classes of diseases. Iron Regulatory Disorders: Iron is an essential metabolite required in the body. Iron is involved in the oxidative phosphorylation, transport of oxygen from lungs to the tissues and also in muscles for diffusion and storage of oxygen. Chronic inflammation due to diseases such as Tuberculosis and AIDS cause systemic iron deficiency and Anemia of Inflammation. Excess iron is toxic to the cells as it causes oxidative damage to macromolecules. Mutations in the iron regulatory network genes are known to cause a class of diseases known as Hereditary Hemochromatosis. These two models help us understand systemic iron homeostasis in vertebrates. Using drug screens in these models we have discovered drug candidates that reverse the disease phenotypes and recover iron levels. Birth Defects: CHARGE syndrome is a birth defect that affects a number of different tissues. C: Coloboma of the eye H: Heart anomalies A: Atresia of choanae R: Retardation of growth and development E: Ear abnormailes The genetic model of CHARGE syndrome in zebrafish exhibits defects in the same tissues. The molecular dissection of this model has helped us discover hitherto unknown functions of the gene. |
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