Beitel GJ et al. (1994) Worm Breeder's Gazette "An ACEDB For the Macintosh User Group"

Beitel GJ, Horvitz HR

[Worm Breeder's Gazette, 1994]

An ACEDB for the Macintosh User Group Greg Beitel (BEITEL@MIT.EDU) and H. R. Horvitz, DepL Biology, MIT, Cambndge, MA 02139, USA

Beitel GJ et al. (1992) Worm Breeder's Gazette "The Synthetic Multivulva Gene lin-9 Encodes a Novel Protein"

Horvitz HR, Beitel GJ

[Worm Breeder's Gazette, 1992]

THE SYNTHETIC MULTIVULVA GENE lin-9 ENCODES A NOVEL PROTEIN Greg Beitel and Bob Horvitz HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA (617) 253-5820

Ahamed, Tosif et al. (2017) International Worm Meeting "The chaotic worm: Capturing the continuous complexity of natural behavior in the movement of C. elegans."

Stephens, Greg, Ahamed, Tosif

[International Worm Meeting, 2017]

Animal behavior is often thought to be composed of discrete stereotyped motifs and stochastic transitions between them. This view has been strengthened by recent studies that utilize advances in Machine Learning to map the behavioral motifs for several different model animals, inlcuding C. elegans. However, this discrete description is only an approximation, and doesn't take into account the variability within each motif. Here, we propose an alternative description of C. elegans behavior based on the fact that it is fundamentally a continous dynamical system. The equations of any dynamical system define a flow in a phase space and the behavior of the system can be completely described by the properties of this flow. We leverage the low dimensional space of C. elegans postures to reconstruct the dynamical phase space of C. elegans locomotion and study the resulting flow. We show that the dynamics lie in a 6 dimensional phase space, which is globally composed of three sets of cyclic trajectories that form the animal's most stereotyped behaviors: forward, backward and turning locomotion. In other words, these 6 numbers tell us almost everything about worm locomotion: whether it's going forward, backward or making a turn; the speed at which it's moving, its turning rate, its wave frequency and amplitude etc. In this sense, the 6D phase space provides an almost complete description of C. elegans behavior. In contrast to the global stereotypy, we also observe substantial local variability, i.e. every body wave the animal makes is different in the detail. Surprisingly, our tests reveal that simple noise models cannot account for the observed behavioral variability. Instead, we find that the variability is due to the chaotic nature of the flow, arising from exponential divergence of neighboring trajectories in the phase space. Further analysis of the phase space flow reveals even more surprises. We find that C. elegans dynamics, although chaotic, are highly constrained. In fact, they turn out to be closely associated with Hamiltonian systems, a well understood class of dynamical systems that conserve energy. We propose that the connection with Hamiltonian dynamics might underlie the flexibility and efficiency of C. elegans behavior. In summary, we have come up with a mathematically precise description of C. elegans behavior that is not only complete but due to its geometric nature it is also simple and intuitive. Our analysis reveals that the coexistence of stereotypy and variability in C. elegans behavior is a result of chaotic dynamics and not due to stochastic flucturations. Finally, we expect that combined with remarkable progress in whole brain imaging of freely-behaving worms, this work will provide a precise and quantitative guide to neural and genetic control of behavior in C. elegans.

Ahamed, Tosif et al. (2017) International Worm Meeting "The deterministic dynamics of random search in C. elegans."

MARUYAMA, Ichiro, Ahamed, Tosif, Stephens, Greg

[International Worm Meeting, 2017]

Foraging C. elegans actively modulate their search strategy to effectively sample their environment. These decisions are based on statistical distributions of food patches in the environment, sensory cues and their recent experience. Examples of C. elegans search behaviors include area restricted search, salt chemotaxis and roaming-dwelling. Studies based on centroid measures have suggested a random search framework to explain these behaviors. Within this framework, worms sample an environment by executing straight runs punctuated randomly by sharp turns made by reversals, omega turns or a combination of both. When the frequency of sharp turns is high, worms perform a diffusive search, densely sampling a small area. On the other hand when the frequency of sharp turns is small, they perform a ballistic search, going straight for a long period of time. In this study we take another look at random search in C. elegans by analyzing the continuous dynamics in the low dimensional space of C. elegans postures given by the eigenworm representation. To our surprise, we find that the randomness in random search is largely a result of deterministic chaos instead of sensory or motor noise. Thus, the chaotic nature of the dynamics implies that the behavior of the worms is not random, but predictable for a finite period of time. This prediction window is governed by a quantity called the Maximal Lyapunov Exponent (MLE), which is positive for chaotic systems. Highly chaotic systems have a small prediction window due to a large MLE, while, weakly chaotic systems have a big prediction window resulting from a small MLE. We find that for worms engaged in an area restricted search, the MLE gradually reduces with time as the worms transition from a diffusive search strategy to a ballistic search strategy. Moreover, the reversal frequency of these worms is positively correlated with the MLE, consistent with the observation that worms get more predictable as they reduce their reversal frequency. Furthermore, the variation in MLE enough to describe most of the random search behavior, suggesting the intriguing possibility that only one degree of freedom underlies control of C. elegans foraging behavior. Finally, we use this theoretical framework to probe the biology of random search by studying the roles of monoamines dopamine and serotonin in foraging. In summary, we extend past theoretical work on C.elegans random search by including detailed postural dynamics and find that deterministic chaotic dynamics underlie the apparent randomness of C.elegans search strategies. Our analysis also suggests that the MLE of the dynamics is potentially the only parameter that the worm controls to modulate its search strategy and decide how predictable or unpredictable it wants to be.

Gomez-Marin, Alex et al. (2015) International Worm Meeting "Compressibility quantifies the stereotypy and complexity of C. elegans locomotion."

Gomez-Marin, Alex, Stephens, Greg, Brown, Andre

[International Worm Meeting, 2015]

There has been increasing interest in unbiased methods for quantifying behaviour and C. elegans' simple morphology makes it a useful animal for testing new approaches. We have recently described a method of representing locomotion as a sequence of transitions between a set of discrete template postures. This makes it possible to enumerate the full variety of observed behavioural motifs in a systematic way. Here we combine the discrete representation with a hierarchical compression algorithm to quantify the complexity and stereotypy of spontaneous locomotion of a large set of mutants and wild isolates. More stereotyped, repetitive locomotion is more compressible than more random, uncoordinated behaviour. We find that most wild isolates show more stereotyped locomotion than N2, but that this difference is not explained by npr-1 since an npr-1 loss of function mutant shows behaviour that is approximately as complex as N2.

Helms, Stephen J et al. (2013) International Worm Meeting "A Common Behavioral Model Underlies the Motility of a Diverse Set of Nematodes."

Avery, Leon, Helms, Stephen J, Shimizu, Thomas S, Stephens, Greg J

[International Worm Meeting, 2013]

Animal behavior emerges from many layers of biological organization-from molecular signaling pathways and neuronal networks to mechanical outputs of muscles. Naively, the large number of interconnected variables at each of these layers would seem to imply dynamics that are complex and hard to control or even tinker with. Yet, for organisms to survive in a competitive, ever-changing environment, behavior must readily adapt. We have quantitatively characterized motile behavior in a diverse set of nematodes spanning the lab strain C. elegans N2 to wild strains and distant species. Using high-resolution imaging, we measured the centroid trajectory and body shape dynamics of individual worms moving on agar plates surrounded by a repellant boundary. We found that a simple physical model accounting for variable speed, stochastic reversal events, and an anomalously diffusing bearing can describe all the tested species. Furthermore, these behaviors are driven by conserved patterns in the postures adopted by the worms. Finally, we found that the behavioral parameters varied over time, among individuals, and across strains and species in a correlated way that is consistent with a trade-off between exploratory and exploitative behavior. This suggests a surprisingly simple underlying mechanism controlling variation in motile behavior that matches likely relevant ecological constraints.

Helms, Stephen et al. (2015) International Worm Meeting "A Roaming-Dwelling Axis Dominates Variation in Motile Behavior Across Nematode Species."

Shimizu, Tom, Helms, Stephen, Carlos-Costa, Antonio, Avery, Leon, Stephens, Greg

[International Worm Meeting, 2015]

A quantitative understanding of organism-level behavior requires predictive models that can capture the richness of behavioral phenotypes, yet are simple enough to extract functional and mechanistic insights. A key challenge is to develop and interpret such models in an unbiased manner. Behavior combines elements of randomness and determinism, thus requiring extensive data sets from well-controlled laboratory experiments to avoid biases in sampling its statistical repertoire. On the other hand, the biological significance of the extracted quantitative features needs to be interpreted in the broader context of its ecology and physiology. We developed an experimental setup and analysis protocol that allows us to extract at high throughput the translational trajectories and body postures of many individual nematode worms over extended times. We applied this system to characterize a panel of strains originating from diverse ecological contexts, including the canonical lab strain C. elegans N2, additional wild isolates of C. elegans, and other species spanning a large portion of the nematode phylum. From this rich quantitative dataset, we found that trajectory statistics of all tested worms could be described by a common random-walk model with independent dynamics in the speed and bearing. Differences across strains and species, as well as between individuals within each strain, are captured by variation in the seven parameters that completely describe the model. Cross-species comparisons of extracted parameters revealed that the principal mode of variation is in the degree of spatial exploration (corresponding to 'roaming' and 'dwelling' behaviors). We are now extending this work to include the higher-resolution dynamics of the worm's body postures. Our approach combining data-driven modeling with cross-species comparisons provides an objective means of identifying biologically relevant patterns of behavioral variation and simple statistical models that will be instrumental for future mechanistic studies of behavioral control.

Helms, Stephen et al. (2015) International Worm Meeting "Quantitative Behavioral Measurements of Individual Aging Worms Reveal Lifespan-Altering Insulin Pathway Mutants Do Not Affect Healthspan."

Lezzerini, Marco, Lohrmann, Esther, Koers, Jana, Shimizu, Tom, Stephens, Greg, Helms, Stephen, Budovskaya, Yelena

[International Worm Meeting, 2015]

Animals exhibit complex behaviors that emerge from the coordinated function across multiple scales of an organism: from genetics to neurons and physiology. Therefore, quantitative behavioral measurements can provide insight into the overall 'health' of an organism. We have developed a high-throughput imaging experiment to measure the motility and posture of individual worms on agar with food over their entire adult life. These data allow for a rich statistical characterization of the behavior of individual worms and how such behavior changes over time. We used this new imaging experiment to compare behavioral changes during aging in wild-type and the classic lifespan-affecting insulin pathway mutations: daf-2 (CF1580, twice as long), daf-16 (CF1874, slightly shorter), and daf-2/daf-16 (CF1588, slightly shorter). Each mutation was backcrossed into the sod-3::GFP reporter strain (CF1553) to ensure no spurious mutations had accumulated. For each strain, we performed two independent experiments assaying 24 worms for an hour 16 times over 31 days. In related work, we developed a parameterized model of motility. Using this model, we found that aging was associated with a decrease in exploratory motility and a progressive slowing of behavior. While we did observe the expected changes in lifespan, all of the strains showed a similar and reproducible decline in behavior as the worms aged. A number of recent studies have underscored the view that changes in lifespan are not necessarily associated with changes in aging-related functional decline ('healthspan'). Our result confirms that the increased lifespan in daf-2 is not accompanied by an increase in healthspan, and provides a detailed view of how behavior changes with age. Furthermore, this work demonstrates the power of our experimental system and automated analysis for rapid behavioral phenotyping.

Ward S et al. (1980) Worm Breeder's Gazette

Ward S, Hogan E, Roberts TM

[Worm Breeder's Gazette, 1980]

A polypeptide which comigrates with worm muscle actin on 1-D and 2-D gels can be isolated from purified sperm. Careful quantitation of the Coomassie blue staining of this peptide using rabbit actin as a standard reveals that this putative actin is only 0.02% of the sperm's protein. It can be detected easily on autoradiograms of 2-D gels of 35s labelled sperm, it is barely detectable on Coomassie blue stained gels, but is strongly stained with the new silver stain. It comigrates exactly with muscle actin on the gel systems we have tried so far. It is probably in the sperm because it is not labelled by external surface labelling. Greg Nelson and Yair Argon found that by indirect immunofluorescence staining of spermatozoa with anti-actin antibodies, only the pseudopods stained. We do not know how it contributes to sperm motility.

Jennifer B Phillips et al. (2001) International C. elegans Meeting "mir-1 and mir-2 exhibit defects in pronuclear migration and spindle orientation in the P0 stage C. elegans embryo"

Jennifer B Phillips, Rebecca Lyczak, Bruce Bowerman

[International C. elegans Meeting, 2001]

The position of the first mitotic spindle in the C. elegans embryo is crucial for establishing the cellular asymmetry necessary for proper patterning . Events such as pronuclear migration, centration, and rotation of the centrosome/nuclear complex are important precursors to proper spindle orientation, but remarkably little is known about the machinery which enacts these processes. To investigate the genes responsible for these and other early events, we screened for temperature sensitive embryonic lethal mutations with defects in P 0 spindle orientation. We isolated alleles of mel-26, zyg-9, rot-2 (see abstract by Greg Ellis) , and dnc-1 (see abstract by John Willis), in addition to two new loci we have named mir-1 and mir-2 , for pronuclear mi gration and P 0 r otation defective. In mir-1 and 2 mutant embryos, the maternal pronucleus often fails to migrate to the posterior of the embryo before the first mitotic spindle sets up. In these embryos, the maternal DNA may not be integrated into the mitotic apparatus, and instead seems to be randomly segregated to one of the daughter cells, appearing as an extra nucleus. The pronuclei do not centrate in these mutants, and the centrosome/nuclear complex does not rotate, resulting in a posteriorly positioned, transversely oriented spindle and a cleavage plane through the long axis of the embryo. Initial polarity appears normal, but cytoplasmic determinants are subsequently mislocalized due to the aberrant cleavage plane. I am working to characterize these migration and rotation defects in detail, using time lapse video microscopy, immunocytochemistry, and GFP fusion lines in which we can visualize tubulin and histone in living embryos. mir-1 and 2 map to chromosomes I and II, respectively. I am continuing to map each mutant to small intervals on these linkage groups, and will be employing RNAi and transgenic rescue to clone mir-1 and mir-2 .