Biology subjects

Malaiwong, N.

Publications and source records attributed to Malaiwong, N..

7 recordsLinked to original sources

bioRxiv2026

An ancient monoaminergic signaling system coordinates contractility in a nerveless sponge

Chemical neurotransmission was a key animal innovation, enabling multicellular coordination of physiology and locomotion. Sponges are early-diverging animals that lack neurons and muscles, yet still coordinate contraction and relaxation of their filter-feeding water canals. Here, we show that Spongilla lacustris synthesizes the monoamines tryptamine, phenethylamine, and tyramine to elicit distinct canal behaviors. We identify previously uncharacterized decarboxylases and vesicular transporters coexpressed in secretory neuroid and metabolic cells. Using phosphoproteomics and label-free 3D imaging, we show that tryptamine activates GPCR signaling and Rho GTPases, remodeling adhesion and actomyosin networks in contractile canal epithelia to drive localized constrictions and whole-body deflations. Together, these findings define an ancestral monoaminergic system linking secretory and contractile cell types that predate neurons and was later elaborated for neuromodulation of synaptic transmission.

evolutionary biology↗

bioRxiv2026

Cell-specific roles for the conserved Galpha chaperone RIC-8 in cilia biology

Primary cilia exhibit conserved organization and contain structural and functional domains of unique molecular composition. The inversin compartment (InvC), which is found in the proximal ciliary segment of a subset of vertebrate and invertebrate cell types, concentrates different classes of signaling molecules. Mutations in genes encoding resident proteins of the InvC manifest in ciliopathies, highlighting the importance of the InvC in cilia biology. We previously showed that a chaperone of G proteins RIC-8 localizes to the InvC of C. elegans channel cilia; however, the mechanisms that regulate RIC-8 targeting to this ciliary sub-domain or RIC-8 function in the InvC remain unknown. Here, we build on our prior work to demonstrate that RIC-8 becomes restricted to the InvC during larval development and show that, while the RVxP motif and intact transition zone are required for its proper intraciliary distribution, RIC-8 localization to the cilium depends on intraflagellar transport. Using the ASH neuron as a model, we establish that RIC-8 modulates chemosensory responses mediated by channel cilia. Finally, we show that human RIC8A and RIC8B proteins are required for ciliogenesis in RPE-1 cells. Collectively, our results define ciliary trafficking mechanisms and novel functions for a highly conserved signaling protein.

cell biology↗

bioRxiv2026

FLInt 2.0: Robust and customizable single shot integration in C. elegans

Transgenesis in Caenorhabditis elegans has revolutionized biological research by enabling the precise control of expression of both endogenous and exogenous genes. The FLInt (Fluorescent Landmark Interference) method was developed to accelerate site-specific integration of transgenes, but persistent false-positive events during screening have emerged as a rate-limiting step. Here, we present an alternative FLInt strategy, FLInt 2.0, that reduces false positives by biasing Cas9 cutting of the tdTomato and Cbr unc-119(+) safe-harbor locus, adjacent to the untranslated region (3 UTR). The design preserves fluorescence during non-integrative repair events, such that only true integration of an extrachromosomal array abolishes tdTomato expression. We demonstrate that this targeted approach maintains high integration efficiency while significantly decreasing the proportion false positives observed in F1 progeny. Molecular and transmission analyses confirm that non-fluorescent F2 animals reliably represent stably integrated multi-copy transgenic lines, which can be tailored to desired expression levels using a simple subsequent Cas9 targeting approach. By exploiting coding-frame geometry to discriminate integration events from repair-induced artifacts, this method streamlines the identification of the true integrants, reducing labor-intensive screening and increasing experimental throughput. Our strategy provides a robust, visually guided, and efficient refinement of FLInt, offering a generalizable framework for improving site-specific transgene integration in C. elegans.

genetics↗

bioRxiv2025

Nuclear receptor-neurotransmitter coupling links behavior to metabolic state

Animals must flexibly respond to environmental stimuli to survive, and optimal responses critically depend on the organisms current needs. Many organisms have evolved both cell-intrinsic and intertissue signaling pathways that integrate metabolic status. However, how this information is encoded in molecular signals is currently not well understood. Here we show that the nematode C. elegans employs lipidated neurohormones that combine the neurotransmitter octopamine and fat metabolism-derived building blocks to relay information about lipid metabolic status and drive inhibition of aversive olfactory responses during food removal. Using targeted metabolomics, we show that lipidated neurohormone synthesis requires the carboxylesterase CEST-2.1, which links octopamine-glucosides with endogenous methyl-branched or diet-derived cyclopropane fatty acids that act as agonists of the nuclear receptor and master regulator of fat metabolism, NHR-49/PPAR. Loss of cest-2.1, loss of bacterial cyclopropane fatty acid production, or loss of endogenous biosynthesis of the methyl-branched fatty acid substrates of CEST-2.1 mimics the behavioral responses of animals lacking octopamine, indicating that regulation of neurotransmitter-dependent behavior is linked to the coordination of fat metabolism via NHR-49/PPAR. Biosynthesis and subsequent neuromodulation via lipidated neurohormone relies on an intertissue trafficking pathway in which octopamine is shuttled first into the intestine where it is chemically modified, which is likely followed by neuronal import and intracellular hydrolysis to finally release free octopamine. We propose that esterase-dependent synthesis and subsequent hydrolysis of lipidated neurohormones represents a chemical encoding mechanism by which animals integrate information from neurotransmitter signaling and lipid homeostasis to direct appropriate behaviors.

neuroscience↗

bioRxiv2024

Mechanical load conditions the spectrin network to `run-on' proteolysis and promotes early onset neurodegeneration

The correct homeostasis of the neuronal cytoskeleton and its dynamics is important for health and disease. Forces constantly act on the neurons in our body, leading to subtle axonal deformations and length changes. The spectrin cytoskeleton is known as a key player that protects neurons against mechanical damage. How the spectrin cytoskeleton changes with age and how it influences mechanoprotection in aging animals is not well understood. Using an interdisciplinary approach, we show that age causes a loss of proprioception during the first few days of adulthood in C. elegans via spectrin unfolding, loss of mechanical tension and degradation of the spectrin cytoskeleton. Guided by a proteomic screen to identify potential spectrin binding partners, we found that this early-onset neurodegeneration can be suppressed in clp-1 mutants and by targeted expression of an engineered chaperone derived from human B-crystallin. Our data suggest that the spectrin cytoskeleton is sensitized to proteolytic damage by calcium-sensitive proteases when mechanical stresses conspires with high-calcium concentrations as in proprioceptive signaling. These results may have implications for the etiology of diseases in which high calcium dynamics and mechanical stress co-incide.

neuroscience↗

bioRxiv2023

FLInt: Single Shot Safe Harbor Transgene Integration via Fluorescent Landmark Interference

The stable incorporation of transgenes and recombinant DNA material into the host genome is a bottleneck in many bioengineering applications. Due to the low efficiency, identifying the transgenic animals is often a needle in the haystack. Thus, optimal conditions require efficient screening procedures, but also known and safe landing sites that do not interfere with host expression, low input material and strong expression from the new locus. Here, we leverage an existing library of{approx} 300 different loci coding for fluorescent markers that are distributed over all 6 chromosomes in Caenorhabditis elegans as safe harbors for versatile transgene integration sites using CRISPR/Cas9. We demonstrated that a single crRNA was sufficient for cleavage of the target region and integration of the transgene of interest, which can be easily followed by loss of the fluorescent marker. The same loci can also be used for extrachromosomal landing sites and as co-CRISPR markers without affecting body morphology or animal behavior. Thus, our method overcomes the uncertainty of transgene location during random mutagenesis, facilitates easy screening through fluorescence interference and can be used as co-CRISPR markers without further influence in phenotypes.

genetics↗

bioRxiv2021

Mechanical Stretch Inhibition SensitizesProprioceptors to Compressive Stresses

A repetitive gait cycle is an archetypical component within the behavioural repertoire of many if not all animals including humans. It originates from mechanical feedback within proprioceptors to adjust the motorprogram during locomotion and thus leads to a periodic orbit in a low dimensional space. Here, we investigate the mechanics, molecules and neurons responsible for proprioception in Caenorhabditis (C.) elegans to gain insight into how mechanosensation shapes the orbital trajectory to a well-defined limit cycle. We used genome editing, force spectroscopy and multiscale modeling and found that alternating tension and compression with the spectrin network of a single proprioceptor encodes body posture and informs TRP-4/NOMPC and TWK-16/TREK2 homologs of mechanosensitive ion channels during locomotion. In contrast to a widely accepted model of proprioceptive stretch reception, we found that proprioceptors activated under compressive stresses in vivo and in vitro, and speculate that this property is conserved across function and species.

neuroscience↗