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Iyer, S. S.

Publications and source records attributed to Iyer, S. S..

21 records · Page 2Linked to original sources

Intrinsic Disorder and Degeneracy in Molecular Scale Organization of Biological Membrane

The scale-rich spatiotemporal organization in biological membrane dictates the \"molecular encounter\" and in turn the larger scale biological processes such as molecular transport, trafficking and cellular signalling. In this work, we explore the degeneracy in lateral organization in lipid bilayer systems from the perspective of energy landscape theory. Our analysis on molecular trajectories show that bilayers with lipids having in-vivo characteristics have a highly frustrated energy landscape as opposed to a funnel-like energy landscape in in-vitro systems. Lattice evolution simulations, with Hamiltonian trained from atomistic trajectories using lipids topology and non-affine displacement measures to characterize the extent of order-disorder in the bilayer, show that the inherent frustration in in-vivo like systems renders them with the ability to access a wide range of nanoscale patterns with equivalent energy penalty. We posit that this structural degeneracy could provide for a larger repository to functionally important molecular organization in in-vivo settings.

biophysics↗

The NSL complex mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise

Nucleosomal organization at gene promoters is critical for transcription, with a nucleosome-depleted region (NDR) at transcription start sites (TSSs) being required for transcription initiation. How NDR and the precise positioning of the +1 nucleosome is maintained on active genes remains unclear. Here, we report that the Drosophila Non-Specific Lethal (NSL) complex is necessary to maintain this stereotypical nucleosomal organization at promoters. Upon NSL1 depletion, nucleosomes invade the NDRs at TSSs of NSL-bound genes. NSL complex member NSL3 binds to TATA-less promoters in a sequence-dependent manner. The NSL complex interacts with the NURF chromatin remodeling complex and is necessary and sufficient to recruit NURF to target promoters. The NSL complex is not only essential for transcription but is required for accurate TSS selection for genes with multiple TSSs. Further, loss of NSL complex leads to an increase in transcriptional noise. Thus, the NSL complex establishes a canonical nucleosomal organization that enables transcription and determines TSS fidelity.

genomics↗

Using Topological Rearrangements to Characterize De-mixed Liquid Phases in Bio-membranes

Lateral heterogeneities in biomembranes play a crucial role in various physiological functions of the cell. Such heterogeneities lead to demixing of lipid constituents and formation of distinct liquid domains in the membrane. We study lateral heterogeneities in terms of topological rearrangements of lipids to identify the liquid-liquid phase coexistence in model membranes. By quantifying the degree of non-affine deformation associated with individual lipid, we are able to characterize the liquid ordered (Lo) and liquid disordered (Ld) phases in model lipid bilayers, without any prior knowledge about the chemical identity of the lipids. We explore the usage of this method on all atom and coarse-grained lipid bilayer trajectories. This method is helpful in defining the instantaneous Lo-Ld domain boundaries in complex multi-component bilayer systems.\n\nThe characterization is also used to highlight the effect of line-active molecules on the phase boundaries and domain mixing. Overall, we propose a framework to explore the molecular origin of spatial and dynamical heterogeneity in biomembrane systems, which can be exploited not only in computer simulations but also in experiments.

biophysics↗