Biology subjects

Sudhanand, M.

Publications and source records attributed to Sudhanand, M..

3 recordsLinked to original sources

bioRxiv2026

Leucine Regulates Neuronal Health During Nutrient Deprivation in Caenorhabditis elegans

Alterations in nutrient availability induce changes in neuronal structure and connectivity across species, ultimately leading to nervous system plasticity and behavioural changes. However, it remains unclear how prolonged acute nutrient deprivation affects the integrity and function of the nervous system. Using the nematode Caenorhabditis elegans, we uncovered that prolonged macronutrient deprivation profoundly impacts neuronal health. Across developmental stages, multiple sensory neuron classes in the C. elegans nervous system, including polymodal IL2, volatile odor-sensing AWB and AWC, and CO2-sensing BAG neurons, display extensive dendritic and axonal blebbing, severely disorganized dendritic, axonal, and cell body morphologies, and severely disrupted chemical and electrical synaptic organization during prolonged nutrient deprivation. The severity of these defects increases progressively with the duration of nutrient deprivation, ultimately affecting animal behaviours. Our results show that the availability of a particular macronutrient, specifically the branched-chain amino acid leucine alone, in the absence of any other macronutrients, although insufficient to support animal growth, is sufficient to completely prevent nutrient-deprivation-mediated neuronal damage and the decline in animal behavioural responses. Moreover, leucine supplementation alone is sufficient to reverse nutrient-deprivation-mediated neuronal abnormalities. These findings suggest that the availability of leucine, rather than absolute caloric intake, is crucial for maintaining neuronal health and function under adverse conditions.

neuroscience↗

bioRxiv2026

An Improved Protocol for High-Efficiency and Cost-Effective CRISPR/Cas9-Mediated Knock-ins in C. elegans

CRISPR/Cas9-mediated homology-directed precise genome editing using long single-stranded DNA (ssDNA) donors has expanded the possibilities for generating defined genetic modifications. However, the required ssDNA donor preparation can be technically demanding and often requires extensive locus-specific sequence design. Here, we examined parameters influencing ssDNA donor-mediated genome editing and developed approaches to simplify donor preparation using {lambda}-exonuclease-mediated ssDNA generation. By evaluating donor designs across multiple genomic loci, we found that efficient genome editing can be achieved with relatively short homology regions for a range of insertion sizes. These findings provide a basis for simplifying ssDNA donor preparation and the overall gene-editing pipeline, potentially facilitating its application across species.

molecular biology↗

bioRxiv2025

Molecular Configuration, Regulation and Function of Heterochannel Electrical Synapses

Neuron-specific expression of particular gap junction channel components defines the configuration and functional properties of electrical synapses. However, how a neuron utilises multiple, simultaneously expressed channel proteins - connexins or innexins -to make meaningful connections with distinct synaptic partners remains largely unknown. Using the posterior mechanosensory circuit in C. elegans, we discovered that individual electrical synapses can be formed by clustering together molecularly distinct gap junction channel-types made of three different innexin proteins, INX-1, UNC-7, and UNC-9. In this previously unknown configuration, which we term as heterochannel synapses, molecularly distinct gap junction channel types functionally collaborate to regulate posterior touch sensory behaviour, enhancing functional robustness. We show that the synaptic trafficking of the molecularly different channel types within a heterochannel synapse is independently regulated by discrete and conserved kinesin motor proteins, while distinct molecular pathways involving channel-specific retrograde kinesins regulate their turnover. These independent, channel-specific regulations also make individual synapse-level alterations in the composition of heterochannel synapses possible under altered environmental conditions, providing a novel mechanism for electrical synapse plasticity. Finally, we present evidence of heterochannel electrical synapses in C. elegans locomotory circuits and in the cerebellar Purkinje neurons of zebrafish larvae. Altogether, we demonstrate a novel heterochannel organization of electrical synapses, their regulation, and functional importance, which may be a conserved feature of metazoan nervous system.

neuroscience↗