Digvijay Singh
K99 & Damon Runyon Postdoctoral Fellow
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I am fascinated by biology at the molecular level. The key to some of the most pressing challenges in healthcare lies in a thorough understanding of the molecular basis of life-forming biomolecular complexes. The two critical components of the molecular basis are how these complexes work in real-time (i.e., their function and assembly) and what they look like at the molecular or submolecular level (Structural Biology). Good knowledge of these two components enhances our understanding of fundamental biology. Furthermore, this understanding gives us a blueprint for the therapeutic strategies to control/manage the behavior of these complexes and, in turn, the fate of the cell/organism itself.

Investigating these dual components is akin to playing legos at the molecular level, i.e., a play of seeing which parts of a complex are joined together or interact and what they look like. For investigations into these dual components, I specialize in the following two techniques:

  • Single-molecule biophysics
  • Cryo-electron microscopy, chiefly the In situ tomography using cryo-focused ion beam milling

On a personal front, I enjoy spending time with my family, playing Tennis, and Swimming. Some of the issues I care about are Animal welfare, Democratization of science, Climate change, Minimalism, and Anti-Wastage.


My academic geneology (incomplete)

Publications

Cryo-Focused Ion Beam Milling of Cells

The Molecular Architecture of the Nuclear Basket

Integrative spatiotemporal map of nucleocytoplasmic transport

Comprehensive structure and functional adaptations of the yeast nuclear pore complex

A viral genome packaging ring-ATPase is a flexibly coordinated pentamer

Effects of individual base-pairs on in vivo target search and destruction kinetics of bacterial small RNA

HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells

The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein

Real-time observation of Cas9 postcatalytic domain motions

Preparing samples from whole cells using focused-ion-beam milling for cryo-electron tomography

Single molecule analysis of effects of non-canonical guide RNAs and specificity-enhancing mutations on Cas9-induced DNA unwinding

Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a)

Mechanisms of improved specificity of engineered Cas9s revealed by single-molecule FRET analysis

Understanding the Molecular Mechanisms of the CRISPR Toolbox Using Single Molecule Approaches

The Single-Molecule Centroid Localization Algorithm Improves the Accuracy of Fluorescence Binding Assays

Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9

Determination of in vivo target search kinetics of regulatory noncoding RNA

An Improved Surface Passivation Method for Single-Molecule Studies

Protein stability and folding kinetics in the nucleus and endoplasmic reticulum of eucaryotic cells