Life Sciences & Biotechnology
Title : | Delineation of the role of isoforms of kisspeptin in mammalian reproduction |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Antara Banerjee, ICMR- National Institute For Research In Reproductive And Child Health, Maharashtra |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | antarabnrj@gmail.com |
Equipments : | Minifuge |
Details
Executive Summary : | The neuropeptide kisspeptin-1 (KISS1) and its cognate G-protein coupled receptor (GPCR), the kisspeptin-1 receptor (KISS1R) are the gatekeepers of the hypothalamic-pituitary-gonadal (HPG) reproductive axis. The signaling of KISS1 through KISS1R triggers the secretion of gonadotrophin-releasing hormone (GnRH) in the hypothalamus, thus inducing puberty. KISS1-KISS1R interaction also modulates other reproductive functions in the life span of an individual like ovulation, implantation and placentation, menopause in females; spermatogenesis in males. Interestingly, KISS1 is a product of the KISS1 gene which undergoes proteolytic processing from an initial 145 amino acid peptide to give rise to 54-mer, 14-mer, 13-mer and 10-mer isoforms each sharing a common C-terminal decapeptide sequence.Not much is known about the physiological significance of these KISS1 isoforms. Thus, a detailed investigation into understanding the binding and signaling profiles of each of these KISS1 isoforms with the KISS1R is essential, given their central role in mammalian reproduction. Scientific objectives 1. To carry out in silico molecular docking of isoforms of KISS1 with KISS1R 2. To investigate the phospho protein signalling signatures downstream to activation of KISS1R with the isoforms of KISS1 3. To investigate the lipid signalling signatures downstream to activation of KISS1R with the isoforms of kisspeptin Hypothesis The neuropeptide KISS1 modulated the neuroendocrine control of fertility as well as metabolism. The presence of isoforms of KISS1 indicate that they may serve overlapping as well as discrete functions. However, this has not been studied in detail and needs to be explored in order to identify distinct signaling signatures that can be attributed to each isoform. Experiments Molecular docking of each isoform of KISS1 with KISS1R will be carried out in silico. The profile of protein kinases as well as the lipidome (lipid signaling pathways) downstream to activation of KISS1R expressing cells stimulated with each of the isoforms of KISS1 will be delineated. Significance of the study This study will help in characterizing the isoforms of kisspeptin by studying their receptor binding and signaling properties which may help in understanding their biological relevance. |
Total Budget (INR): | 31,81,787 |
Organizations involved