Our model system ~ Drosophila melanogaster
The fruit fly, Drosophila is an excellent genetic model organism. It shows remarkable similarity of genes, basic molecular and cellular mechanisms, metabolic pathways and physiological systems with higher organisms like mammals. Our group is trying to identify novel factors involved in the physiological maintenance of nutrient and energy balance using fruit flies. We use a combination of approaches in our lab:
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Large-scale genetic screens.
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Genetic tools including RNAi libraries, microRNA sponge libraries.
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Tissue and stage-specific drivers.
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In-vivo reporters for signalling pathways and neural activity.
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Metabolic assays - triglyceride, glycogen and hemolymph glucose assays.
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Various molecular biology and biochemical techniques.
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Cell biology and imaging techniques.
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Automated Drosophila activity monitors and behavioral assays.
Drosophila insulin-producing neurons and fatbody
In higher vertebrates, the hypothalamic arcuate nucleus, a key region of the brain, controls food intake and energy utilization. A region functionally and developmentally similar to hypothalamus exists in the Pars intercerebralis region of Drosophila brain, which is rich in neurosecretory cells. Among these neurosecretory cells (NSCs), a group of 14 insulin-producing cells (IPCs) play prominent roles in regulating growth, metabolism, life-span, fecundity and stress resistance. Ablation of these neurons leads to phenotypes in flies that resembles diabetes and obesity. Drosophila genome encodes for 8 insulin-like peptide (dilp) genes, of which dilp2, dilp3 and dilp5 are expressed almost exclusively by the neuronal IPCs. The IPCs receive signals regarding nutrient and metabolic status of the organism from the fatbody, an organ functionally orthologous to mammalian liver and adipocytes. Further, the fatbody derived signals regulate the expression of dilp genes and secretion of DILPs from the IPCs. Insulin signalling mechanisms are highly conserved in metazoans, similar to insulin in other higher vertebrates DILPs acts on various insulin responsive cells in the nutrient storage, neural and endocrine tissues, through the insulin receptor (InR) and activate a complex cell-signalling cascade resulting in growth and regulation of metabolic pathways. Insulin is also known to act as a satiety hormone, has been implicated in learning, memory, ageing and neurodegeneration across a wide-range of species. Drosophila, classically used for developmental studies, thus provides a fantastic model system to study the genetic mechanisms of physiology and metabolism.
We are currently investigating novel signaling pathways and gene regulatory mechanisms that control the functions of Drosophila insulin-producing cells and fatbody during phases of growth, maturation and ageing. We are also investigating the neural and endocrine mechanisms that regulate hunger induced behavior and activity in adult flies. Our group’s research focuses on mechanisms that are conserved in bilaterians, which will help us in understanding the evolution of genetic processes that maintain nutrient and energy homeostasis. Furthermore, our approaches will help to unravel novel regulatory mechanisms and neural circuitry that aids in nutrient balance. Thus, a central theme in biology will be addressed in my lab, which may enable us to understand metabolic diseases better.
Keywords: Drosophila, nutrition, metabolic pathways, microRNAs, insulin-signaling, ecdysone, neural regulation, feeding behavior, ageing, neurodegeneration
