Research Projects

The neuro-architecture of brain, not only consists of neurons, but is provided with its developmental paradigm via the network of glial cells as well. It is known that after generation, neurons lose the mitotic nature of cell division whereas glial cells retain it. Evidence exists that glia act as neural progenitors and facilitators of synaptic plasticity as glia can regulate neuronal development and physiology. One of the challenges of studying genetic, molecular and mechanistic aspects related to glial cells, is the methodological limitations of being able to study nervous system related aspects in greater detail within higher mammalian models. Genetic models like C. elegans offer multiple advantages in terms of studying neuronal as well as glial cells in context of their functional aspects. The nervous system of C. elegans consists of 302 neurons, 50 glial cells derived from neuronal/epithelial progenitors, and six glial cells that are mesodermally derived. Glial processes are found at neuronal junctions at every level: at sensory receptive endings, at neuron-neuron synapses, and at neuromuscular junctions, raising the intriguing notion that glia in C. elegans may be primarily involved in intercellular information transfer, an idea that is supported by several lines of evidence. We propose to employ C. elegans model, that exhibits immense advantages in terms of studying neuronal as well as glial cells with profound ease of carrying out genetic manipulations towards identifying critical genetic and proteomic events providing key to understand whether it could be possible to counter neuronal death via “reprogramming glial cells to either trigger neurogenesis” or to “reprogram themselves as neurons”. More specifically, we wish to study the “basic helix loop helix transcription family” that not only guides embryonic neurogenesis and axon development, but its evolutionarily conserved members such as human Olig2 (C. elegans orthologue hlh-17) controls neurons over the entire life span. We also intend to study ptr-10, a protein that is specifically enriched in glial cells. Specifically we intend to address the following objectives: (1) To study the function of hlh-17 and ptr-10, which are expressed in CEPsh glia, in the context of protein aggregation and dopamine signaling in transgenic C. elegans. (2) To explore the role of ptr-10 and hlh-17, the two proteins enriched in C. elegans glial cells, in context of neurodegeneration/ neuronal repair and to study the transcriptomic profile under the knockdown condition of ptr-10 and hlh-17. (3) To carry out conditional activation of host factors towards studying reprogramming of glial cells into neurons within the conditions of dying neuronal subtypes.