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CSIR-NCL, Pune

From Sequence to Function: Decoding Biological Mysteries and Personalized Therapies at NCL Pune

The Bioinformatics Center at CSIR-NCL, Pune, serves as a comprehensive resource center dedicated to teaching and engaging in the modeling and data analysis of biology across various scales. The center's focus is to tackle diverse challenges in biology by effectively employing sequence analysis, molecular modeling, network analysis, and reaction modeling. One of the primary objectives is to develop methodologies addressing gene regulation, encompassing expression and post-translational modifications. Researchers are actively involved in analyzing NFkB post-translational regulation https://doi.org/10.1093/genetics/iyac081 and modeling the impact of mutant VAMP-associated protein on dimerization and tetramerization properties. To enhance accessibility to research findings, the center is developing web resources for curating and analyzing datasets from simulations, experiments, and clinical data. They have established a resource for predicting essential genes https://presgene.ncl.res.in/ preprint at doi.org/10.1101/2022.11.25.517801 .

The center has introduced PRESGENE, a machine learning-based web application designed for predicting essential genes in unexplored eukaryotic and prokaryotic organisms. Through molecular modeling, they have elucidated the roles of post translational modifications, specifically palmitoylation in GLP 1R, a G protein-coupled receptor (GPCR) crucial in diabetes treatment. The web-based tool, PRESGENE is a combination of supervised and semi-supervised machine learning pipelines for predicting essential genes with high accuracy. The algorithms mitigate the problems of training dataset imbalance and limited availability of experimentally labelled data for essential genes. The center excels in applying modeling and data analysis approaches across various scales, from molecular fragments to proteins, cells, and organisms, with particular expertise in sequence analysis.

Collaborating with teams at IISER Pune and CSIR-IGIB, New Delhi, the Center engages in National Network Programs (NNPs) that integrate experimental and theoretical/computational approaches to study biological systems. Operational since November 2022, the center has initiated work on developing integrative models for gene regulation, collaborated with experimentalists on new models for biological pathways, and created online tools for executing previously published algorithms for identifying essential genes. In addition to research activities, the center is establishing outreach programs and workshops to train students, fostering connections with industries. They have organized lectures by researchers from both industry and academia and conducted a one-day hands-on training session for 50 participants.

The center collaborates with IISER Pune and CSIR-IGIB, New Delhi, to investigate the misregulation of GATA transcription factors. This family of transcription factors is implicated in multiple disorders prevalent in the Indian population, including myocardial infarction, cancer, susceptibility to infections, and certain developmental defects. Given that misregulation can occur at various stages of gene expression, the center employs a multi-pronged systems-understanding approach, with the hope of contributing to the development of appropriate, personalized therapies.

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Some of the participants and instructors at DBT-BIC@NCL workshop on modeling using ODEs

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