Drosophila Eye Model to Study Neurodegeneration

Date of Award

2018

Degree Name

Ph.D. in Biology

Department

Department of Biology

Advisor/Chair

Advisor: Amit Singh

Abstract

The term neurodegeneration refers to the progressive loss of neurons leading to the onset of irreversible neurodegenerative disorders like the Alzheimer's disease (AD). We have harnessed the genetics of the Drosophila melanogaster a.k.a fruit fly to elucidate the complex network of genetic and molecular mechanisms underlying neurodegeneration. We exploited the vast plethora of sophisticated genetic tools available at our disposal to mimic the neurodegenerative disease in the fly eye.Alzheimer's disease is a common form of dementia with no cure to date. One of the hallmarks of this disease is the accumulation of Amyloid plaques that triggers neuronal death. The Amyloid Precursor Protein (APP) is a trans-membrane protein which when properly cleaved forms a 40 amino acid long polypeptide but when improperly cleaved forms a 42 amino acid long polypeptide (A▀42) which is hydrophobic in nature. We believe that once these A▀42 plaques are formed they emanate certain signals that cause the healthy neurons to die. Thus it is important to identify these signals in order to delay the onset of the A▀42 mediated neurodegeneration. In order to ascertain the molecular and genetic mechanisms underlying the A▀42 mediated neurodegeneration in Alzheimer's disease several animal models have been developed. We have utilized the Drosophila eye model to understand the etiology of the disease by identifying genetic and chemical modifiers that could ameliorate the A▀42 mediated neurodegenerative phenotype. Here we discuss about one such modifier Wingless (Wg) which when downregulated or blocked rescues the A▀42 mediated neurodegeneration.A complete understanding of a disease-associated brain requires the analysis of the individual neurons. Studies till now have focused on understanding the onset of Alzheimer's disease by misexpressing the Alzheimer associated proteins in a certain group of cells with the help of the yeast derived GAL4-UAS system. In order to understand how the A▀42 plaques produced in a small group of neurons slowly spreads across the entire brain, we must understand the crosstalk between the plaque forming neurons and the surrounding healthy neurons. We thus have generated a two-clone system in order to study the fate of the surrounding wild type neurons and have seen that the A▀42 misexpressed neurons grow at the expense of the adjacent wild type neurons.

Keywords

Biology, Genetics, Neurosciences, Neurodegeneration, Drosophila, eye

Rights Statement

Copyright © 2018, author

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