About

Aravinthan Samuel is a Professor of Physics at Harvard University within the Department of Molecular & Cellular Biology. His research focuses on understanding how animals acquire and transform sensations into neural representations and memories, and how they calculate and execute decisions based on recent and past experiences. His work involves studying brain and behavior in the roundworm C. elegans and the Drosophila larva, utilizing advances in light and electron microscopy to map, manipulate, and monitor neural circuits that link brain and behavior in these small creatures.

Research topics

• Biology
• Neuroscience
• Psychology
• Genetics
• Evolutionary biology
• Cognitive psychology
• Biological system
• Nanotechnology
• Physics
• Materials science
• Biophysics

Selected publications

• The dynamic response of the bacterial flagellar motor to its direct intracellular input signal

  Proceedings of the National Academy of Sciences · 2026-03-03

  articleOpen accessSenior authorCorresponding

  navigates chemical gradients, the motor switches from counterclockwise (CCW) during forward swimming to clockwise (CW) during direction-changing tumbles. The motor responds indirectly to extracellular chemosensory input to membrane-bound chemoreceptors using an intervening intracellular signaling pathway. How the motor responds to its direct input signal-the diffusible messenger phosphorylated CheY (CheY-P)-remains poorly understood. Steady-state motor measurements have been modeled as an allosteric switch between CCW/CW states that depends on mean CheY-P levels. Allosteric models have suggested that as many as 20 CheY-P molecules can be bound to the motor when it switches rotational direction. But steady-state models cannot predict the sensitivity of the motor to dynamic changes in CheY-P that essentially modulate chemotactic behavior. We present an optogenetic reagent that precisely controls the direct dynamical input signal to the motor. We designed a "caged" molecule, Opto-CheY, that is transiently activated by photon absorption. We find that activation and binding of one to three additional CheY-P molecules is sufficient to switch the motor from the CCW to CW state. The sensitivity of the motor to small changes in CheY-P occupancy helps resolve a long-standing paradox about the high sensitivity of the chemotactic response to external sensory input. Optogenetic biochemistry by light-activated uncaging of signal molecules is a new strategy to dissect information-processing in the living cell.

  PublisherDOI

• Efficient pheromone navigation via antagonistic detectors in Caenorhabditis elegans male

  Nature Communications · 2026-02-13

  articleOpen access

  Chemotaxis to a moving potential mate that emits a volatile sex pheromone poses a navigation challenge requiring rapid, precise responses to maximize reproductive success. Volatile chemicals form gradients that differ from soluble compounds, potentially making navigation based on comparisons between spatially separated sensors unreliable for small-bodied animals. Here we show that, rather than a simple spatial comparison, Caenorhabditis elegans males employ an antagonistic strategy, comparing inputs from sex-shared head (AWA) and male-specific tail (PHD) sensory neurons with distinct response properties. Despite sharing a receptor, SRD-1, these detectors play different roles: AWAs promote forward movement and acceleration, while PHDs induce reversals and deceleration. In rising pheromone gradients, AWA activity dominates; in falling gradients, AWA inactivates, allowing PHD to correct trajectories. AWAs are essential for mate-searching, while PHDs are crucial for complex tasks. A minimal computational model reproduces these behaviors and infers how head-tail signals are combined. Thus, a sexually dimorphic, antagonistic sensory system enables adaptive navigation in dynamic environments.

  PublisherDOI

• Permeabilization with fenchone enhances cryopreservation of <i>Drosophila</i> embryos

  Biology Letters · 2026-03-18

  articleOpen access

  The difficulty of cryopreservation has long been a limitation of Drosophila melanogaster as a genetic model organism. Here, we report a statistically significant improvement in the efficiency of Drosophila cryopreservation by substituting limonene with the monoterpenoid fenchone in the embryo permeabilization step of a previously published method. We found that fenchone-permeabilized embryos exhibit greater uptake of cryoprotectant compared with those permeabilized by limonene, and an approximately sixfold increase in the rate of egg-to-adult survival for wild-type flies. Using this improved protocol, we successfully cryopreserved and revived precious strains after 12 months of storage in liquid nitrogen. These results suggest that fenchone is a superior permeabilizing agent for fly embryo cryopreservation, expanding possibilities for the long-term maintenance of Drosophila and other insect species. Further refinement of this approach may enable cryopreservation to replace continuous culture as the method of choice for routine maintenance of fly stocks.

  PublisherDOI

• Permeabilization with fenchone enhances cryopreservation of <i>Drosophila</i> embryos

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-08

  preprintOpen access

  Abstract The difficulty of cryopreservation has long been a limitation of Drosophila melanogaster as a genetic model organism. Here we report a statistically significant improvement in the efficiency of Drosophila cryopreservation by substituting limonene with the monoterpenoid fenchone in the embryo permeabilization step of a previously published method. We found that fenchone-permeabilized embryos exhibit greater uptake of cryoprotectant compared with those permeabilized by limonene, and a ~6-fold increase in the rate of egg-to-adult survival for wild-type flies. Using this improved protocol, we successfully cryopreserved and revived precious strains after 12 months of storage in liquid nitrogen. These results suggest that fenchone is a superior permeabilizing agent for fly embryo cryopreservation, expanding possibilities for the long-term maintenance of Drosophila and other insect species. Further refinement of this approach may enable cryopreservation to replace continuous culture as the method of choice for routine maintenance of fly stocks.

  PublisherOA PDFDOI

• Analysis of smart imaging runtime

  Han-guk hyeonmigyeong hakoeji/Applied microscopy · 2025-08-14 · 2 citations

  articleOpen access

  Smart microscopy is a new imaging approach that involves rapid imaging, prediction of important subregions, then selective re-imaging. This approach has been validated in reducing imaging beam time in electron microscopy connectomics, but the speedup depends on various imaging workflow parameters. Here we present the first runtime analysis of traditional vs. smart microscopy and show how these parameters can magnify, or diminish potential time savings. We provide a GUI application that calculates the theoretical time savings of smart microscopy from user input parameters describing their imaging workflow. Finally, we measure end-to-end runtime of SmartEM acquisition on an electron microscope to demonstrate two strategies for faster acquisition: mixed-precision neural networks and parallelization of microscope and support computer operations.

  PublisherDOI

• Torque-generating units of the bacterial flagellar motor are rotary motors

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-29

  preprintOpen accessSenior authorCorresponding

  E. coli swims using helical flagellar filaments driven at their base by a rotary motor. Torque-generating ‘stator’ units drive the bacterial flagellar motor (BFM) by transmitting mechanical power to a cytoplasmic ‘rotor’, the C-ring. Each stator unit is a proton-conducting heteromer. A central dimer of two MotB proteins anchor to the cell wall. A surrounding pentamer of five MotA proteins transmit mechanical power to the C-ring. This asymmetrical 5:2 structure is consistent with rotation as the mechanism of torque generation. Here, we test the hypothesis that the MotA 5 MotB 2 stator units are rotary motors themselves and interact with the rotor like intermeshed gearwheels, where rotation of the C-ring is directly coupled to MotA 5 rotation around the MotB 2 . We used in vivo polarized photo-bleaching microscopy. When a subset of fluorescent domains inside a multimer is rapidly photo-bleached by a strong pulse of polarized light, the induced polarization-dependent fluorescence of unbleached domains becomes a reporter of angular orientation. We applied polarized photo-bleaching microscopy to tethered cells rotating by single flagellar motors. We probed fluorescently-labeled MotA pentamer and MotB dimer calibrated to motor rotation. The MotB dimer rotates at the same angular speed as the cell body, consistent with its anchor to the cell wall. The MotA pentamer rotates ∼6.2x faster than the flagellar motor, revealing the gear ratio between stator and rotor. Significance Statement Bacteria swim by rotating rigid helical flagellar filaments. Here, we find that the torque-generating unit that drives flagellar rotation is itself a rotary motor. Each torque-generating unit is a heteromeric macromolecular machine – a pentamer of MotA subunits that surround a dimer of proton-conducting MotB subunits. Torque is generated as the MotA spins around MotB. The MotA pentamer interacts with rotor of the flagellar motor in a manner resembling intermeshing gearwheels. The bacterial flagellar motor is driven by the first set of enmeshed gearwheels that has been described in any living cell.

  PublisherOA PDFDOI

• EM-Compressor: Electron Microscopy Image Compression in Connectomics with Variational Autoencoders

  Lecture notes in computer science · 2025-01-01 · 3 citations

  book-chapterOpen access

  The ongoing pursuit to map detailed brain structures at high resolution using electron microscopy (EM) has led to advancements in imaging that enable the generation of connectomic volumes that have reached the petabyte scale and are soon expected to reach the exascale for whole mouse brain collections. To tackle the high costs of managing these large-scale datasets, we have developed a data compression approach employing Variational Autoencoders (VAEs) to significantly reduce data storage requirements. Due to their ability to capture the complex patterns of EM images, our VAE models notably decrease data size while carefully preserving important image features pertinent to connectomics-based image analysis. Through a comprehensive study using human EM volumes (H01 dataset), we demonstrate how our approach can reduce data to as little as 1/128th of the original size without significantly compromising the ability to subsequently segment the data, outperforming standard data size reduction methods. This performance suggests that this method can greatly alleviate requirements for data management for connectomics applications, and enable more efficient data access and sharing. Additionally, we developed a cloud-based application named EM-Compressor on top of this work to enable on-the-fly interactive visualization: https://em-compressor-demonstration.s3.amazonaws.com/EM-Compressor+App.mp4 .

  PublisherDOI

• Thermoregulation: Tactics for navigating thermal gradients

  Current Biology · 2025-11-01

  articleSenior author
  PublisherDOI

• The larval <i>Drosophila</i> mushroom body balances lateralized sensing and interhemispheric integration

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-02

  preprintOpen accessSenior author

  larva, olfactory receptor neurons project largely ipsilaterally, providing a tractable system for asking where and how interhemispheric integration arises downstream. We combined volumetric calcium imaging with unilateral sensory perturbations, connectomic analysis, and optogenetic manipulations to trace the propagation of left-right olfactory information across successive layers of the olfactory system. This approach implicates the mushroom body (MB) as a key substrate for interhemispheric integration of odor representations. Kenyon cell (KC) odor responses were almost entirely ipsilateral, indicating minimal functional coupling between the two MBs at the input level. In contrast, modulatory neurons (MBINs) exhibited highly symmetric responses to unilateral stimulation, suggesting that reinforcement signals are broadly shared across hemispheres. Nevertheless, odor responses in some MB output neurons (MBONs), up to 5 synapses downstream from the sensory periphery, preserve information about stimulus laterality. Moreover, we show that asymmetric activation of these MBONs can modulate the animal's turning behavior in a side-biased manner. Finally, we provide direct evidence that larvae can exploit instantaneous spatial comparisons for navigation in certain sensory contexts. These findings suggest that the deeply lateralized architecture of the larval olfactory system balances the need for interhemispheric integration with the advantages of parallel sensory processing.

  PublisherOA PDFDOI

• Torque-generating units of the bacterial flagellar motor are rotary motors

  Proceedings of the National Academy of Sciences · 2025-12-03 · 1 citations

  articleOpen accessSenior authorCorresponding

  Escherichia coli swims using helical flagellar filaments driven at their base by a rotary motor. Torque-generating “stator” units drive the bacterial flagellar motor by transmitting mechanical power to a cytoplasmic “rotor,” the C-ring. Each stator unit is a proton-conducting heteromer. A central dimer of two MotB proteins anchors to the cell wall. A surrounding pentamer of five MotA proteins transmits mechanical power to the C-ring. This asymmetrical 5:2 structure is consistent with rotation as the mechanism of torque generation. Here, we test the hypothesis that the MotA 5 MotB 2 stator units are rotary motors themselves and interact with the rotor like intermeshed gearwheels, where rotation of the C-ring is directly coupled to MotA 5 rotation around the MotB 2 . We used in vivo polarized photobleaching microscopy. When a subset of fluorescent domains inside a multimer is rapidly photobleached by a strong pulse of polarized light, the induced polarization-dependent fluorescence of unbleached domains becomes a reporter of angular orientation. We applied polarized photobleaching microscopy to tethered cells rotating by single flagellar motors. We probed fluorescently labeled MotA pentamer and MotB dimer calibrated to motor rotation. The MotB dimer rotates at the same angular speed as the cell body, consistent with its anchor to the cell wall. The MotA pentamer rotates <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <mml:mo>∼</mml:mo> </mml:math> 6.2 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <mml:mo>×</mml:mo> </mml:math> faster than the flagellar motor, revealing the gear ratio between stator and rotor.

  PublisherDOI

Recent grants

• Neural representation of mating partners by male C. elegans

  NIH · $2.6M · 2019–2024

• NIH Grant P01GM103770

  NIH · $12.5M · 2019

• Neural representation of mating partners by male C. elegans

  NIH · $689k · 2019–2024

• NIH Grant DP1OD004064

  NIH · $2.5M · 2013

• A Biophysical Analysis of C. Elegans Thermotactic Behavior in Diverse Environments

  NSF · $430k · 2010–2014

Frequent coauthors

• Mei Zhen

  Mount Sinai Hospital

  58 shared

• Albert Cardona

  MRC Laboratory of Molecular Biology

  38 shared

• Mason Klein

  University of Miami

  34 shared

• Wesley Hung

  Lunenfeld-Tanenbaum Research Institute

  29 shared

• Luis Hernandez-Nunez

  Harvard University

  27 shared

• Daniel Witvliet

  University of Toronto

  27 shared

• Vivek Venkatachalam

  26 shared

• Linjiao Luo

  Institute of Acoustics

  25 shared