Molecular Biophysics Unit (MBU)
Recent Submissions
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Studies on the promoter specificity determinants and modulators of the prokaryotic transcription machinery
Bacteria adapt to a wide range of environmental conditions by synchronizing transcription with changes in the extracellular environment. This is achieved by the synchronized action of two-component systems, Extra Cytoplasmic ... -
Solution structures and interaction studies of mycobacterial MazEF6 toxin-antitoxin system
Toxin-Antitoxin (TA) systems are stress response systems found on plasmids and chromosomes of bacteria and archaea. They are involved in important functions such as plasmid maintenance, programmed cell death, persister ... -
Structural and biochemical studies on mycobacterial Uracil-DNA glycosylase (Ung) and MutT1, key proteins involved in maintaining the genomic integrity in Mycobacteria
Maintaining genomic integrity is indispensable for the survival and propagation of an organism. Failure to do so can cause mutations involving structural and functional aberrations, leading to severe diseases. The causative ... -
Structural insights into assembly and regulation of HigBA toxin-antitoxin system from Escherichia coli
In the last few decades, bacterial Toxin-antitoxin (TA) systems have been identified to play crucial roles in bacterial survival under stressful conditions and virulence. TA systems are pair of genetic elements where one ... -
Insights into the conformational stability & pharmacology of peptides through side chain and backbone modification
The first part of the work presented in the thesis deals with CH-pi interaction, which is a lesser-known non-covalent interaction in proteins. We identified several CH-pi donor-acceptor pairs involving amino acids side ... -
Homeostasis of cyclic-di-AMP in Mycobacterium smegmatis: Functional and structural contributions of c-di-AMP synthase (MsDisA) and hydrolase (MsPDE)
In bacteria, cyclic-di-nucleotide based second messengers regulate various physiological processes including the stress response. For the past decades, cyclic diadenosine monophosphate (c-di-AMP) has emerged as a crucial ... -
Mutational sensitivity of CcdB mutants in their native operonic context
Determining the precise effects of thousands of point mutants on protein structure, stability, and activity is a challenging task. Chapter 1 introduces how next-generation sequencing technologies exploit phenotypic screens ... -
Robustness of Neural Activity Dynamics in the Medial Entorhinal Cortex
Biological systems exhibit considerable heterogeneity in their constitutive components and encounter stochasticity across all scales of analysis. Therefore, central questions that span all biological systems are: (a) How ... -
Mechanistic insights into protein stabilization and protein-protein interactions
Most amino acid substitutions in a protein either lead to partial loss of function or are near neutral. Several studies have shown the existence of second-site mutations that can rescue the defects caused by diverse loss ... -
Structural, mechanistic and pharmacological studies of inhibitory neurotransmitter transporters
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). The synaptic levels of GABA are controlled by the activity of GABA transporters (GATs) present in the presynaptic ... -
Structural and Biophysical studies to evaluate the influence of oligomerization on biomolecular function
Oligomeric proteins are more common than monomers. This aspect of molecular evolution substantially contributes to functional diversity and the acquisition of features such as cooperativity and regulatory mechanisms. Not ... -
Structural and functional insights of biological macromolecules associated with infectious diseases – single particle cryo-electron microscopy based studies
In the global context, particularly in India, the two most important infectious diseases among many others are Tuberculosis (TB), an age-old disease and COVID-19, a new-age disease. This thesis focuses on some of the key ... -
First thorough characterization of the structure, interactions and specificity of an archeal lectin with implication for TB infection
Decades long studies on plant lectins carried out in this laboratory have contributed substantially to glycobiology and helped in the initiation and development of macromolecular crystallography in India. Subsequently the ... -
Probing Protein Sequence-Function Relationships using Deep Mutational Scanning
Deep Mutational Scanning (DMS) approaches help elucidate sequence-function-phenotype relationships in proteins, which ultimately improves our understanding of residue (or nucleotide)-specific contributions to protein ... -
Exploring Nature's Inventory: Investigating the Role of Amide to Thioamide Substitution on Protein Stability
The peptide backbone holds a protein together and plays a crucial role in guiding its three-dimentional structure. The tertiary structure of proteins regulates several biological processes. Therefore, peptide bond modification ... -
Identification, characterization, structure, and assembly of type III toxin-antitoxin systems from Escherichia coli
Bacteria adopt several defense strategies to enable their survival against the environmental threats they encounter from time to time. Toxin-antitoxin (TA) systems are being understood as a key bacterial defense mechanism ... -
Integrative modeling of NS3 helicase function with molecular kinetics, molecular simulations and machine learning
The viral NS3 helicase is a crucial enzyme involved in the RNA replication of positive strand ssRNA viruses of the Flaviviridae family. The NS3 is an active motor that binds RNA and couples ATP hydrolysis to the mechanical ... -
HIV-1 and SARS-CoV-2 immunogen design
Human Immunodeficiency Virus (HIV-1) is the aetiologic agent of AIDS. Presently there are ~38 million HIV-1 infected individuals worldwide and ~1 million deaths in 2019. Since its discovery, the quest for vaccine candidate ... -
Development of quantitative RNA sequencing methods to understand RNA variant diversity.
The advent of next-generation sequencing (NGS) has accelerated biological research by providing the opportunity to connect genome level sequence information to function. One key application of NGS has been analysis of gene ... -
Protein-small molecule interactions: Structural insights and applications in computational drug discovery
Deviation from normal healthy conditions, termed as disease, can often be triggered due to the malfunctioning of proteins. Modulating the functions of proteins by administering therapeutic agents (drugs) may alleviate the ...