A5078636404- Advanced Fluorescence Microscopy Techniques
- Photosynthetic Processes and Mechanisms
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Cellular transport and secretion
- Biotin and Related Studies
- Microtubule and mitosis dynamics
- Plant Molecular Biology Research
- Click Chemistry and Applications
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- Epigenetics and DNA Methylation
- Lipid metabolism and biosynthesis
- Neuroscience of respiration and sleep
- Plant Reproductive Biology
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Metabolomics and Mass Spectrometry Studies
- Molecular Junctions and Nanostructures
Johns Hopkins University
2016-2023
All India Institute of Medical Sciences
2023
Johns Hopkins Medicine
2016-2018
University of Illinois Urbana-Champaign
2014-2017
Center for Genomic Science
2014
Tata Institute of Fundamental Research
2011
The mammalian target of rapamycin (mTOR) kinase is a master regulator cellular, developmental, and metabolic processes. Deregulation mTOR signaling implicated in numerous human diseases including cancer diabetes. functions as part either the two multisubunit complexes, mTORC1 mTORC2, but molecular details about assembly oligomerization mTORCs are currently lacking. We use single-molecule pulldown (SiMPull) assay that combines principles conventional assays with fluorescence microscopy to...
Protein folding and unfolding are complex phenomena, it is accepted that multidomain proteins generally follow multiple pathways. Maltose-binding protein (MBP) a large (a two-domain, 370-amino acid residue) bacterial periplasmic involved in maltose uptake. Despite the size, has been shown to exhibit an apparent two-state equilibrium bulk experiments. Single-molecule studies can uncover rare events masked by averaging studies. Here, we use single-molecule force spectroscopy study mechanical...
Heterochromatic domains are enriched with repressive histone marks, including H3 lysine 9 methylation, written by methyltransferases (KMTs). The pre-replication complex protein, origin recognition complex-associated (ORCA/LRWD1), preferentially localizes to heterochromatic regions in post-replicated cells. Its role heterochromatin organization remained elusive. ORCA recognizes methylated H3K9 marks and interacts KMTs, G9a/GLP Suv39H1 a chromatin context-dependent manner. Single-molecule...
Significance Transcriptional regulation of the rDNA cluster is a tightly regulated process owing to cellular demand for ribosomal subunits. Dysregulation biogenesis associated with genomic instability and tumor progression. Nucleolar-remodeling complex (NoRC) has emerged as key in maintenance repression. However, mechanisms that regulate association NoRC gene loci are yet be understood. We unravel role B ANP, E 5R, N ac1 (BEN) domain-containing transcription repressor, BEND3, regulating...
Abstract The CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIPIII) transcription factors (TFs) were repeatedly deployed over 725 million years of evolution to regulate central developmental innovations. START domain this pivotal class regulators was recognized 20 ago, but its putative ligands and functional contributions remain unknown. Here, we demonstrate that the promotes HD-ZIPIII TF homodimerization increases transcriptional potency. Effects on output can be ported onto heterologous TFs,...
Abstract Deciphering complex biological processes markedly benefits from approaches that directly assess the underlying biomolecular interactions. Most commonly used to monitor protein-protein interactions typically provide nonquantitative readouts lack statistical power and do not yield information on heterogeneity or stoichiometry of protein complexes. Single-molecule pull-down (SiMPull) uses single-molecule fluorescence detection mitigate these disadvantages can quantitatively interrogate...
Cellular contractility is governed by a control system of proteins that integrates internal and external cues to drive diverse shape change processes. This controller includes myosin II motors, actin crosslinkers protein scaffolds, which exhibit robust cooperative mechanoaccumulation. However, the biochemical interactions feedback mechanisms remain unknown. Here, we use proteomics approach identify direct interactors two key nodes in social amoeba Dictyostelium discoideum: crosslinker...
Recognition of signaling phospholipids by proteins is a critical requirement for the targeting and initiation many cascades. Most biophysical methods measuring protein interactions with use purified proteins, which do not take into account effect post-translational modifications other cellular components on these interactions. To potentially circumvent problems, we have developed single-molecule fluorescence approach to analyzing lipid-protein in crude cell extracts. As proof principle this...
Telomeres are maintained by telomerase or in a subset of cancer cells homologous recombination (HR)-based mechanism, Alternative Lengthening (ALT). The mechanisms regulating telomere-homeostasis ALT remain unclear. We report that replication initiator protein, Origin Recognition Complex-Associated (ORCA/LRWD1), localizing at the ALT-telomeres, modulates HR activity. ORCA's localization to ALT-telomeres is facilitated its interaction SUMOylated shelterin components. loss ORCA ALT-positive...
The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and 2 to maintain cellular organismal homeostasis. Failure finely tune activity results in metabolic dysregulation disease. While there is substantial understanding molecular events leading mTORC1 activation at lysosome, remarkably little known about what terminates signaling. Here, we show that AAA + ATPase Thorase directly binds mTOR, thereby orchestrating disassembly inactivation mTORC1. disrupts...
Background: Prospective evaluation of optical coherence tomography (OCT) and OCT angiography (OCT-A) characteristics in different stages papilledema idiopathic intracranial hypertension (IIH). Methods: In this prospective, observational study patients IIH with were recruited divided into 3 groups—early/established (Group 1), chronic 2), atrophic 3). Peripapillary retinal nerve fiber layer (RNFL) macular ganglion cell inner plexiform (GC-IPL) recorded on OCT. perfusion was documented at...
Abstract HD-ZIPIII transcription factors (TFs) were repeatedly deployed over 725 million years of evolution to regulate central developmental innovations. The START domain this pivotal class regulators was recognized twenty ago, but its putative ligands and functional contributions remain unknown. Here, we demonstrate that the promotes TF homodimerization increases transcriptional potency. Effects on output can be ported onto heterologous TFs, consistent with principles via capture. We also...
Sudden Infant Death Syndrome (SIDS) is the sudden, unexplained passing of an infant during sleep within first year life. The diagnosis SIDS one exclusion, with no plausible explanation following autopsy and investigation death scene. Most our present understanding comes from epidemiological studies, much less known about molecular etiology. One candidate mechanism that abnormalities in brainstem biochemistry cause altered neural control breathing, leading to rousing defect apparent SIDS....
Protein kinase B (PKB)/AKT is a serine/threonine with wide range of essential functions in cell proliferation, survival, differentiation, and metabolism. Growth factor stimulation phosphoinositide‐3 (PI3K) results generation phosphatidylinositol‐3,4,5‐trisphosphate [PI(3,4,5)P 3 ] or PI(3,4)P 2 at the plasma membrane, which recruits AKT. At membrane AKT phosphorylated activated, subsequently dissociates from translocates to cytoplasm nucleus order phosphorylate its targets. Hence, it...