Research Projects

Neuroblastoma (NB) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of paediatric cancer deaths and it originates from undifferentiated Neural Crest Cells (NCCs). NCCs are multipotent cells that are formed in the early vertebrate embryos and they are known to migrate to diverse locations in the embryo via Epithelial to Mesenchymal Transition (EMT) and differentiate into many diverse vertebrate lineages such as the osteocytes, smooth muscle cells, adipocytes, melanocytes and sympathoadrenal cells, to name a few. EMT is influenced by epigenetic mechanisms such as DNA methylation and histone modifications and apart from its role in normal embryonic development, EMT has also been associated with cancer progression. One factor that is associated with both, epigenetic regulation and cancer, is folate. DNA methylation pattern can get altered due to nutritional influence and folate being one of the important component required for methionine cycle is one such micronutrient that can alter DNA methylation pattern and chromatin configuration. It will be of immense importance to expand our understanding of molecular events responsible for neural crest development from epigenetic point of view. To understand the mechanism of NCC derived embryonic cancer, a question “How is cell fate programmed due to altered epigenetic pattern under folate deprived condition, leading to embryonic cancer?” needs to be answered. To response to this question, time line study of embryonic hours’ onset of NCC and its lineage specific differentiation needs to be studied. For spatiotemporal study of developing embryo, zebrafish is the reliable model organism. Employing suitable model, current project is aimed to understand the role of folate in epigenetic gene regulation of NCC lineage differentiation and neoplasm during fetal programming. sAt experimental ‘0’ hr morpholino will be injected into zygote. These embryos will be used to study NC formation, NCC differentiation and migration at different time interval. Bisulfite DNA methylation and chromosome conformation capture (3C) for three-dimensional conformation of chromatin by examining chromatin looping will be performed. Localization will be done by in situ hybridization.

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