How do you make a nanoparticle that tells you where it is and helps at the same time?
In this episode, we dive into the chemistry behind polydiacetylene (PDA)—a polymer that changes colour when it senses temperature, pH, or stress.
Researchers combined PDA with biodegradable poly(glycerol adipate) to create self-reporting nanoparticles that:
Change colour from blue to red under stress or heat
Track cells and nematodes without any added fluorescent dyes
Degrade naturally via enzymatic action
Carry drugs like usnic acid for therapeutic delivery
It’s a step toward theranostic polymers—materials that diagnose and treat simultaneously, glowing as they go. Even C. elegans joined the test, confirming safe uptake and real-time visibility.
📖 Based on the research article:
“Tailoring the Properties of Polydiacetylene Nanosystems for Enhanced Cell Tracking Through Poly(glycerol Adipate) Blending: an In Vitro and In Vivo Investigation”
Benedetta Brugnoli, Eleni Axioti, Philippa L. Jacob, Nana A. Berfi, Lei Lei, Benoit Couturaud, Veeren M. Chauhan, Robert J. Cavanagh, Luciano Galantini, Iolanda Francolini & Vincenzo Taresco
Published in Macromolecular Chemistry and Physics (2025)
🔗 https://doi.org/10.1002/macp.202500259
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How can a worm’s intestine influence its descendants’ lifespan? This episode explores how lysosomes send metabolic signals through the epigenome to extend longevity across generations.
Researchers found that activating lysosomal lipid metabolism triggers transcriptional up-regulation of a histone variant, H3.3 (his-71), in the intestine. This histone is transported to the germ line, where it’s methylated at K79 by the methyltransferase DOT-1.3. The result is a heritable epigenetic state that promotes longer life across multiple generations of C. elegans.
The work reveals how metabolic signalling through lysosomes interacts with chromatin to link soma and germ line, showing how environmental changes like starvation can shape longevity inheritance.
📖 Based on: Zhang Q., Dang W., Wang M.C. Science (2025). “Lysosomes signal through the epigenome to regulate longevity across generations.” https://doi.org/10.1126/science.adn8754
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How do we measure ageing — and how do we know when it’s happening? In this episode, we explore a fascinating review of C. elegans as a model for understanding the timing, tempo, and variability of ageing.
Drawing on work from multiple studies, the paper discusses:
Why ageing is not a uniform decline, but a staggered process
How traits like movement, reproductive output, stress resistance, and gene expression decline on different timescales
The importance of individual variability even in genetically identical worms
New tools like deep learning, live tracking, and molecular clocks
What this means for developing more reliable biomarkers of ageing
Rather than a one-size-fits-all model, the worm offers a dynamic view of ageing as a distributed process — shaped by environment, genotype, and luck.
📖 Based on the research article:
“Timing is everything: measuring the tempo of ageing in Caenorhabditis elegans”
A. Cram, M.S. Riera & J. T. Nelson
Published in GeroScience (2023)
🔗 https://doi.org/10.1007/s11357-023-00998-w
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Is a wiring diagram enough to understand the brain? In this episode, we dive into how researchers combined whole-brain optogenetic stimulation with calcium imaging in C. elegans to reveal functional neural connections that go beyond the traditional connectome.
Key insights include:
A new functional atlas built from ~23,000 neuron pair experiments
How neuropeptides and extrasynaptic signals contribute to brain activity
Strong functional links often exist without anatomical connections
A data-driven rethinking of how neural signals propagate and integrate
Implications for plasticity, brain evolution, and full-organism modelling
This episode sheds light on how small brains can perform complex processing — by rewiring our assumptions about wiring.
📖 Based on the research article:
“Neural signal propagation atlas of Caenorhabditis elegans”
Francesco Randi, Anuj K. Sharma, Sophie Dvali & Andrew M. Leifer
Published in Nature (2023)
🔗 https://doi.org/10.1038/s41586-023-06683-4
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Worms without eyes shouldn’t see colour — yet C. elegans can. In this episode, we dive into a landmark study that shows how worms use blue-to-amber light ratios to make foraging decisions. When exposed to toxic blue pigments like pyocyanin, worms avoid them — but only under white light. The twist? They do it all without opsins.
We explore:
How worms detect and avoid blue-pigment-secreting P. aeruginosa
Why light potentiates avoidance, but only for certain spectral ratios
How lite-1 and GUR-3 receptors mediate spectral sensitivity
Natural variation in colour preference across wild strains
The discovery that stress-related genes jkk-1 and lec-3 underlie colour-guided behaviour
This episode uncovers a new form of opsin-free colour vision, expanding our understanding of how simple organisms read complex environments.
📖 Based on the research article:
“C. elegans discriminates colors to guide foraging”
Dipon Ghosh, Dongyeop Lee, Xin Jin, H. Robert Horvitz & Michael N. Nitabach
Published in Science (2021)
🔗 https://doi.org/10.1126/science.abd3010
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How does a worm know what’s good for dinner? In this episode, we uncover how C. elegans can distinguish between helpful and harmful microbes — and it’s all down to polyamines. These microbe-produced metabolites act like scent beacons, guiding worms to nutritious bacteria like E. coli while steering them away from pathogens.
We explore:
How chemosensory neurons detect polyamines like cadaverine and putrescine
Why ADF and AWC neurons are tuned to sniff out E. coli-enriched scents
How the AIB interneuron acts as a decision hub for foraging
Why worms lose interest in mutant E. coli strains lacking polyamines
What this tells us about host-microbe interactions and innate sensory coding
📖 Based on the research article:
“Chemosensory detection of polyamine metabolites guides C. elegans to nutritive microbes”
Benjamin Brissette, Lia Ficaro, Chenguang Li, et al.
Published in Science Advances (2024)
🔗 https://doi.org/10.1126/sciadv.adj4387
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Why do C. elegans lay eggs only when food is around? In this episode, we explore a newly uncovered neuromodulatory circuit that links food detection to reproductive behaviour using a clever form of disinhibition. At the heart of this is the AVK interneuron — silenced by dopamine when food is present — which normally blocks egg-laying until conditions are right.
We unpack:
How AVK neurons act as gatekeepers for egg-laying behaviour
Dopamine from food-sensing neurons inhibits AVKs via DOP-3 receptors
AVKs release a cocktail of neuropeptides (PDF-1, NLP-10, NLP-21) that modulate downstream AIY neurons
Functional imaging, CRISPR mutants, and optogenetics map the full food-to-egg pathway
How this reveals general principles of neuromodulation and disinhibition
📖 Based on the research article:
“Food sensing controls C. elegans reproductive behavior by neuromodulatory disinhibition”
Yen-Chih Chen, Kara E. Zang, Hassan Ahamed, Niels Ringstad
Published in Science Advances (2025)
🔗 https://doi.org/10.1126/sciadv.adu5829
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In this episode, we dive into a milestone in C. elegans systems biology — the first application of SILAC-style metabolic proteome labelling in a whole animal. By feeding worms lysine auxotroph E. coli labelled with heavy lysine (Lys8), researchers enabled quantitative proteomics with precision typically reserved for cell culture.
But it gets better — they made it RNAi compatible, allowing side-by-side comparisons of wild-type vs mutant proteomes in the same run.
We discuss:
How worms were labelled with heavy lysine using auxotrophic E. coli
How this enabled 94–97% incorporation of label in just one generation
The creation of RNAi-ready NJF01 bacteria for knockdown and labelling
Case study: NHR-49 loss alters lipid metabolism proteins at scale
Why this approach paves the way for whole-organism proteogenomics
📖 Based on the research article:
“Quantitative proteomics by amino acid labeling in C. elegans”
Fredens, J., Engholm-Keller, K., Giessing, A., Pultz, D., Larsen, M.R., Højrup, P., Møller-Jensen, J., & Færgeman, N.J.
Published in Nature Methods (2011)
🔗 https://doi.org/10.1038/nmeth.1675
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In this episode, we explore a high-tech twist on developmental toxicology. Researchers have combined microfluidic engineering with machine learning to automate the analysis of thousands of C. elegans for chemical toxicity testing — no anaesthetics or low-res imaging required.
Using the vivoChip device and a custom ML model called vivoBodySeg, the team:
Captures 3D images of ~1000 worms from 24 populations at once
Achieves near-human segmentation accuracy (Dice score: 97.8%)
Measures subtle toxicity effects like changes in body size and gut autofluorescence
Identifies EC10 and LOAEL values with high precision
Uses few-shot learning to adapt the model to new worm shapes and sizes
This platform slashes analysis time by 140× and sets a new benchmark for high-throughput New Approach Methodologies (NAMs) in toxicology.
📖 Based on the research article:
“Machine learning-based analysis of microfluidic device immobilised C. elegans for automated developmental toxicity testing”
Andrew DuPlissis, Abhishri Medewar, Evan Hegarty, et al.
Published in Scientific Reports (2025)
🔗 https://doi.org/10.1038/s41598-024-84842-x
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In this episode, we follow Caenorhabditis elegans into the magnetic field. Researchers have developed an elegant way to measure whole-brain neural activity in freely moving worms using a calcium-sensitive MRI contrast agent — a major step toward non-invasive brain mapping at the organism scale.
We explore:
How a genetically targeted MRI probe was used to detect calcium flux across the entire worm brain
The fusion of genetics, MRI physics, and behavioural tracking
Real-time measurements of brain dynamics during natural behaviour
How this technique opens the door to non-invasive neuroimaging in small model organisms
Implications for understanding how global brain states coordinate behaviour
📖 Based on the research article:
“Functional MRI of brain-wide activity in freely moving C. elegans”
Uday A. Ramalingam, Andrew M. Leifer, et al.
Published in Nature (2024)
🔗 https://doi.org/10.1038/s41586-024-08331-x
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In this episode, we climb into the world of nematode architecture — worm towers!
Researchers have now captured Caenorhabditis worms forming vertical towers in nature — self-assembled living structures that help worms hitch rides and bridge gaps as a form of collective dispersal.
We explore:
First real-world evidence of towering in C. elegans and other Caenorhabditis species
Lab experiments that trigger towering in controlled conditions
How worms of all life stages can join towers — not just dauers
Towers that grow, bend, and bridge gaps to reach new environments
How touch alone can trigger towers to transfer en masse to new habitats
📖 Based on the research article:
“Towering behavior and collective dispersal in Caenorhabditis nematodes”
Daniela M. Perez, Ryan Greenway, Thomas Stier, Narcís Font-Massot, Assaf Pertzelan, Siyu Serena Ding
Published in Current Biology (2025)
🔗 https://doi.org/10.1016/j.cub.2025.05.026
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In this episode, we go beyond the famous C. elegans connectome to explore how signal propagation doesn’t always follow the wires. Using powerful whole-brain calcium imaging combined with single-cell optogenetic activation, researchers mapped over 23,000 neuron pairings to build a functional atlas that rewrites parts of the worm’s wiring diagram.
We dive into:
How extrasynaptic neuropeptide signalling connects neurons outside synapses
The discovery of functional connections invisible in the wiring diagram
How C. elegans neural signals propagate both directly and indirectly
The creation of a functional connectome that predicts spontaneous activity better than anatomy alone
The surprising flexibility and plasticity of even simple nervous systems
📖 Based on the research article:
“Neural signal propagation atlas of Caenorhabditis elegans”
Francesco Randi, Anuj K. Sharma, Sophie Dvali & Andrew M. Leifer
Published in Nature (2023).
🔗 https://doi.org/10.1038/s41586-023-06683-4
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In this episode, we travel back to one of the great origin stories in gene regulation: the discovery of lin-4, the first-ever microRNA. In Caenorhabditis elegans, scientists found that tiny non-coding RNAs could silence gene expression by pairing with target mRNAs — launching the entire field of microRNA biology.
We explore:
How lin-4 regulates developmental timing by repressing LIN-14 protein
The discovery of small RNAs (22 and 61 nucleotides) as gene regulators
The first evidence for RNA-RNA antisense interactions controlling translation
Why this work reshaped our understanding of gene expression across species
How a worm taught us that not all genes code for proteins
📖 Based on the research article:
"The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14"
Rosalind C. Lee, Rhonda L. Feinbaum & Victor Ambros.
Published in Cell (1993).
🔗 https://doi.org/10.1016/0092-8674(93)90529-Y
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🔗 www.veerenchauhan.com
In this episode, we track how Strongyloides stercoralis — a human-infective nematode — uses carbon dioxide sensing to navigate both outside and inside its host. This tiny parasite shifts its response to CO₂ depending on life stage: repelled when searching for a host, but attracted once inside.
We explore:
Life-stage-specific behaviour: iL3s flee CO₂, iL3as chase it
How Ss-BAG neurons detect CO₂ via the Ss-GCY-9 receptor
CRISPR-generated mutants that lose their ability to sense CO₂
A new method for creating stable knockout lines in S. stercoralis
How CO₂ helps worms navigate through the bloodstream, lungs, and gut during infection
📖 Based on the research article:
“Carbon dioxide shapes parasite-host interactions in a human-infective nematode”
Banerjee et al., 2025, Current Biology
🔗 https://doi.org/10.1016/j.cub.2024.11.036
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In this episode, we ask: can a heartless worm model arrhythmia? Turns out — yes. Using Caenorhabditis elegans as a stand-in for cardiac muscle, researchers tested the effects of polypyrrole nanoparticles (Ppy NPs) on pharyngeal pumping rhythms, revealing fascinating insights into how bioengineered materials might impact human-like tissues.
We explore:
How the worm pharynx mimics cardiac function
Why mutants with sluggish pumps were rescued by Ppy NPs
Long-lasting effects, even after the nanoparticles were expelled
Calcium imaging showing altered Ca²⁺ dynamics in real time
The power of C. elegans for safe-by-design nanomedicine screening
📖 Based on the research article:
“Arrhythmic Effects Evaluated on Caenorhabditis elegans: The Case of Polypyrrole Nanoparticles”
Sumithra Yasaswini Srinivasan, Pilar Alvarez Illera, Dmytro Kukhtar, et al.
Published in ACS Nano (2023).
🔗 https://doi.org/10.1021/acsnano.3c05245
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In this episode, we explore how Caenorhabditis elegans senses and responds to oxygen — not just by breathing, but by activating a finely tuned cGMP signalling network in real time.
Using genetically encoded biosensors, researchers reveal how rising oxygen levels trigger tonic cGMP and Ca²⁺ responses in O₂-sensing neurons like PQR, and how a web of feedback loops controls these signals to shape behaviour.
We unpack:
The role of soluble guanylate cyclases in detecting O₂
How PDE-1 and PDE-2 form a push-pull system to shape cGMP signals
Surprising individual variability in cGMP responses — even in identical worms
Evidence for cGMP nanodomains and subcellular signal compartmentalisation
How these pathways help worms make behavioural decisions in fluctuating oxygen
📖 Based on the research article:
“In vivo genetic dissection of O₂-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor”
Africa Couto, Shigekazu Oda, Viacheslav O. Nikolaev, Zoltan Soltesz & Mario de Bono
Published in PNAS (2013)
🔗 https://doi.org/10.1073/pnas.1217428110
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In this episode, we dive into a genetic mystery: how can a single gene in plant-parasitic nematodes have thousands of alleles? This study unravels the bizarre behaviour of HYP effectors — genes that help nematodes infect plants but defy traditional genetics.
Using CRISPR, long-read sequencing, and clever maths, the researchers reveal:
This isn’t just about plant pests — it’s a rare glimpse at real-time genome innovation, where diversity is generated with intent, not random chance.
📖 Based on the research article:
“A gene with a thousand alleles: The hyper-variable effectors of plant-parasitic nematodes”
Unnati Sonawala, Helen Beasley, Peter Thorpe, Kyriakos Varypatakis, Beatrice Senatori, John T. Jones, Lida Derevnina & Sebastian Eves-van den Akker
Published in Cell Genomics (2024).
🔗 https://doi.org/10.1016/j.xgen.2024.100580
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In this episode, we rewind to one of biology’s biggest plot twists: RNA interference (RNAi). Scientists found that injecting double-stranded RNA into Caenorhabditis elegans could silence genes powerfully and precisely—far beyond anything single strands could achieve.
This game-changing discovery revealed:
How dsRNA triggers targeted gene shutdown
Why only a few molecules can silence thousands of cells
How gene silencing spreads across tissues
The first clues toward RNA-based therapies that would change medicine forever
📖 Based on the research article:
“Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans”
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver & Craig C. Mello.
Published in Nature (1998).
🔗 https://doi.org/10.1038/35888
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In this episode, we uncover how Caenorhabditis elegans males pick the right mate — by literally feeling for it!
Researchers discovered that body stiffness, controlled by special furrow collagens, acts as a key mechanical cue for contact-mediated mate recognition.
We discuss:
How males detect species, sex, and reproductive stage through touch
Why body stiffness and surface signals must work together for successful mating
Experiments using ruptured worms, chemical treatments, and even 3D-printed bionic worms to test mechanical cues
Why mating is not just about scent or sight — it’s about how a partner feels
📖 Based on the research article:
“Body stiffness is a mechanical property that facilitates contact-mediated mate recognition in Caenorhabditis elegans”
Jen-Wei Weng, Heenam Park, Claire Valotteau, Nathalie Pujol, Paul W. Sternberg & Chun-Hao Chen.
Published in Current Biology (2023).
🔗 https://doi.org/10.1016/j.cub.2023.07.020
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How does a tiny worm coordinate complex escape behaviour? In this episode, we dive into how the neurotransmitter tyramine triggers rapid, coordinated escape in Caenorhabditis elegans. Researchers uncovered that tyramine activates a newly discovered tyramine-gated chloride channel, LGC-55, which suppresses head movements and promotes sustained backward locomotion after anterior touch.
We explore:
How tyramine acts as a classical inhibitory neurotransmitter in C. elegans
The critical role of LGC-55 in controlling head movement and reversal length during escapes
Why tyramine’s control of multiple motor outputs is vital to escaping predatory fungi
How tyramine reshapes neural network dynamics to bias the worm toward rapid retreat
📖 Based on the research article:
“A Tyramine-Gated Chloride Channel Coordinates Distinct Motor Programs of a Caenorhabditis elegans Escape Response”
Jennifer K. Pirri, Adam D. McPherson, Jamie L. Donnelly, Michael M. Francis & Mark J. Alkema.
Published in Neuron (2009).
🔗 https://doi.org/10.1016/j.neuron.2009.04.013
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