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Varma, M. M.

Publications and source records attributed to Varma, M. M..

3 recordsLinked to original sources

Nanopore Electrometry Resolves Peptide Charge Patterns beyond Ionic-Current Blockade

Localized measurements of electric fields offer a promising route to expand the information content of nanopore-based single-molecule sensing beyond conventional ionic-current blockade. Here, using all-atom molecular dynamics simulations with virtual electric-field probes placed around a graphene nanopore, we show that the local electric-field captures the presence, and distribution of charged amino acids as the peptides translocate through the pore. These field signatures create reproducible peptide-specific fingerprints across independent translocation events and enable substantially improved discrimination between peptides compared with ionic-current traces obtained under the same simulation conditions. Our results suggest that localized nanopore electrometry can provide a complementary, information-rich readout of peptide charge order that is largely inaccessible to conventional current blockade-based measurement. This study establishes a simulation-guided framework for integrating nanoscale electrometry with nanopore platforms for future peptide and protein analysis.

biophysics↗

Caenorhabditis elegans sensory neurons modulate pathogen specific responses via HLH-30/TFEB transcription factor and FSHR-1 GPCR axes of immunity

Pattern recognition receptors allow animals to sense microbe associated molecular patterns and mount effective immune responses. It is not clear how Caenorhabditis elegans recognizes pathogenic microbes in absence of classical pattern recognition pathways. Here, we asked if sensory neurons of C. elegans allow it to distinguish between pathogens. Exposure of C. elegans to a Gram positive bacterium Enterococcus faecalis or to a Gram negative bacterium Pseudomonas aeruginosa showed predominantly pathogen-specific signatures. Using nematodes defective in sensory perception, we show that neuronal sensing is essential to mount pathogen specific immune response. OSM-6 expressing, ciliated neurons exert non-cell autonomous control of immune effector production via an OSM-6-FSHR-1 GPCR axis as well as an OSM-6-HLH-30/TFEB transcription factor axis during E. faecalis infection. OSM-6-FSHR-1 axis also controls immune response to P. aeruginosa. In all, this study delineates essential role of sensory perception in the regulation of pathogen-specific immunity in C. elegans.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC=\"FIGDIR/small/609610_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@33aa54org.highwire.dtl.DTLVardef@1f38464org.highwire.dtl.DTLVardef@78c656org.highwire.dtl.DTLVardef@1256266_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Two-component systems regulate swarming in Pseudomonas aeruginosa PA14

Swarming in Pseudomonas aeruginosa is a quorum-dependant motility over semi-solid surfaces. On soft agar, P. aeruginosa exhibits a dendritic swarm pattern, with multiple levels of branching. Swarm patterns vary considerably depending upon the experimental design. In the present study, we show that the swarm pattern is plastic and media dependent. We define several quantifiable, macroscale features of the swarm to study the plasticity observed across media. Further, through a targeted screen of 113 genes encoding two-component system (TCS) components, we show that 44 TCS genes regulate PA14 swarming in a contextual fashion. However, only four TCS genes are essential for swarming. Many swarming-defective TCS mutants are highly efficient in biofilm formation indicating an antagonistic relationship between swarming and biofilm states in P. aeruginosa.

microbiology↗