Biology subjects

Krishnamurthy, V.

Publications and source records attributed to Krishnamurthy, V..

4 recordsLinked to original sources

bioRxiv2026

Interplay of mechanics, growth and viral infection dynamics in a spatially expanding bacterial colony

We investigate the dynamics of the spread of the infection due to a phage- during the range expansion of an E coli colony. We find a rich panoply of spatio-temporal dynamics at large colony-level length scales, arising due to the interplay of mechanical forces, growth and viral infection dynamics at smaller cellular length scales. Strikingly, the phages "surf" the front of the growing bacterial colony by hitchhiking on E coli that are advected due to the growth of bacteria in the colony, resulting in an anisotropic spread of the phages. We identify microscopic processes - of the phage release during lysis (occurring on short millisecond timescales at length scales close to that of a single bacterium) and local nematic alignment of the rod-like E coli bacteria (occurring on timescales comparable to the bacterial growth rate and the length scales of a few bacterial cells) - that enhance the advective effects driving the hitchhiking behavior. Combining our experiments with a mathematical model, we explain the multiple spatio-temporal dynamical regimes - from the coexistence of uninfected bacteria, resistant (lysogenic) cells and phages, to fixed points where the entire population turns resistant or remains uninfected. Our work broaches a new frontier in the investigation of eco-evolutionary processes arising from the mechanical and ecological forces due to the interactions between viruses and their hosts.

biophysics↗

bioRxiv2026

Functional Reorganization of Motor Subcircuits in Parkinson's disease

Parkinsons disease disrupts motor control across multiple body parts, yet the neural mechanisms underlying these impairments remain incompletely defined. We compared resting-state functional connectivity in people with mild-to-moderate Parkinsons disease (n = 58) and neurotypical older adults (n = 24), focusing on regions implicated in internally generated (IG) and externally generated (EG) movement pathways. For our analysis, we leveraged the reproducible NeuroMark independent component template and motor effector-specific mapping of primary motor cortex (M1). Our results reveal both increased and decreased connectivity patterns in Parkinsons disease: M1 subregions associated with control of the leg, hand, and larynx showed robust increases in connectivity exclusively with cerebellar territories, particularly Crus II and Lobules VIIIa/VIIIb. The postcentral gyrus (primary somatosensory cortex) showed primarily increased connectivity with cerebellar regions and the insula. In contrast, the caudate nucleus displayed a mixed profile, with increased connectivity to the superior temporal gyrus and decreased connectivity to the superior medial frontal gyrus and cerebellar Crus II. Our motor effector-specific analysis of disease severity scores (MDS-UPDRS) in people with Parkinsons disease revealed mild impairments across all categories (leg, hand, larynx) but disproportionately greater hand-related deficits, suggesting that some of the observed M1 connectivity differences may be influenced by these behavioral asymmetries. These anatomically precise, effector-specific alterations suggest compensatory recruitment of cerebellar circuits in Parkinsons disease and provide a framework for targeting motor subcircuits in rehabilitation, including dance-based interventions.

neuroscience↗

bioRxiv2023

A Nanoparticle RIG-I Agonist for Cancer Immunotherapy

Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving response to immune checkpoint inhibitors (ICI). However, the potency and clinical efficacy of 5-triphosphate RNA (3pRNA) agonists of RIG-I is hindered by multiple pharmacological barriers, including poor pharmacokinetics, nuclease degradation, and inefficient delivery to the cytosol where RIG-I is localized. Here, we address these challenges through the design and evaluation of ionizable lipid nanoparticles (LNPs) for the delivery of 3p-modified stem-loop RNAs (SLRs). Packaging of SLRs into LNPs (SLR-LNPs) yielded surface charge-neutral nanoparticles with a size of [~]100 nm that activated RIG-I signaling in vitro and in vivo. SLR-LNPs were safely administered to mice via both intratumoral and intravenous routes, resulting in RIG-I activation in the tumor microenvironment (TME) and inhibition of tumor growth in mouse models of poorly immunogenic melanoma and breast cancer. Significantly, we found that systemic administration of SLR-LNPs reprogrammed the breast TME to enhance the infiltration of CD8+ and CD4+ T cells with antitumor function, resulting in enhanced response to PD-1 ICI in an orthotopic EO771 model of triple negative breast cancer. Therapeutic efficacy was further demonstrated in a metastatic B16.F10 melanoma model, with systemically administered SLR-LNPs significantly reducing lung metastatic burden compared to combined PD-1 + CTLA-4 ICI. Collectively, these studies have established SLR-LNPs as a translationally promising immunotherapeutic nanomedicine for potent and selective activation of RIG-I with potential to enhance response to ICIs and other immunotherapeutic modalities.

bioengineering↗

bioRxiv2022

Actomyosin cables position cell cohorts during Drosophila germband retraction by entraining their morphodynamic and mechanical properties

The unfolding and displacement of the germband during Drosophila germband retraction (GBR) accomplish the straightening of the embryonic anterior-posterior axis. The failure of GBR reduces embryonic viability and results in the mispositioning of the embryonic segments and the gastrointestinal tract. Despite its importance, the cellular, molecular and physical mechanisms that govern the unfolding of the germband and ensure the accurate positioning of cell fields within it remain poorly understood. Here, we uncover the requirement of planar polarized, supracellular, tensile actomyosin cables for entraining cellular morphodynamics, cell field positioning and retraction kinematics. Circumferential, non-constricting cables that form during early retraction ensure the coherence of placode-like cell cohorts, pattern medio-lateral gradients in cell shape and sidedness within it, and dampen retraction speed. Linear, constricting cables that power displacement at the end of retraction enable sequential, multi-tissue, collective T1 transitions to reposition medial cell fields to more posterior locations. Together, our results reveal how the spatiotemporally regulated deployment of actomyosin structures, functioning either as barricades or as purse strings, modulate the speed of tissue unfolding and enable cell field positioning by influencing the morphodynamic and mechanical properties of cell cohorts during morphogenesis.

cell biology↗