Research Focus

Drosophila eye model to study axial patterning, cell survival & birth defects.

The fruit fly, Drosophila melanogaster, eye serves as an excellent model to study cell type specification during development. Drosophila eye has been extensively used to address diverse biological processes like patterning cell proliferation, cell death, cell survival, polarity and genetic basis of human diseases.  The compound eye of an adult fly develops from the primordium called eye imaginal disc harbored inside larva, which initiates from a group of 20- cells as early as an embryo.

The two major goals of my laboratory are: 

(I) Study the genetic basis of early eye patterning and growth with emphasis on axial patterning: Dorsal-Ventral patterning in Drosophila eye 

Axial patterning is a key aspect of organogenesis, transforming a single layer of cells into a complex three-dimensional organ. Dr. Singh’s lab is focused on the molecular genetic basis of dorso-ventral (DV) patterning, which represents the initial lineage restriction event in early eye development. DV patterning is crucial for the growth and organization of the eye disc, with distinct dorsal and ventral domains arising from the specific expression of dorsal selector genes and ventral growth-controlling genes. The lab aims to identify new components involved in DV patterning and their role in retinal determination. Their research seeks to enhance understanding of both the normal molecular and genetic processes of eye development and the genes and molecules whose alterations lead to eye birth defects. Our laboratory seeks to provide a better understanding of the molecular, genetic, and environmental basis of normal eye development, as well as elucidate the genes and molecules that when altered result in the genesis of birth defects in the eye. 

(II) Discern the mechanism of complex neuropathological diseases, like Alzheimer’s Disease (AD). 

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder prevalent among the aging population, characterized by a gradual decline in cognitive functions such as learning and memory due to the selective atrophy of specific neuronal populations. A major contributor to AD pathology is the accumulation of amyloid-beta plaques in the brain, specifically amyloid-beta 42 (Aß42), which is toxic and triggers neurodegeneration. Despite the presence of Aß42 in the body, the precise molecular genetic mechanisms leading to neurodegeneration are not fully understood.

To investigate these mechanisms, Dr. Singh’s lab employs a Drosophila eye model to explore the genetic circuitry involved in Aß42-mediated neurodegeneration. The lab’s long-term goals are to (a) identify genetic mutations that contribute to or trigger AD-related neuropathology, which could serve as biomarkers for early detection, and (b) discover potential drug targets that could block the cellular processes leading to amyloid plaque accumulation or prevent the oligomerization of Aß42.