Biology subjects

Alisch, T.

Publications and source records attributed to Alisch, T..

4 recordsLinked to original sources

bioRxiv2024

Drift in Individual Behavioral Phenotype as a Strategy for Unpredictable Worlds

Individuals, even with matched genetics and environment, show substantial phenotypic variability. This variability may be part of a bet-hedging strategy, where populations express a range of phenotypes to ensure survival in unpredictable environments. In addition to phenotypic variability between individuals ("bet-hedging"), individuals also show variability in their behavioral phenotype across time, even absent obvious external cues. There are few evolutionary theories that explain random shifts in phenotype across an animals life, which we term phenotypic drift. We use individuality in locomotor handedness in Drosophila melanogaster to characterize both bet-hedging and drift. We use a continuous circling assay to show that handedness spontaneously changes over timescales ranging from seconds to the lifespan of a fly. We compare the amount of behavioral drift and bet-hedging across a number of different fly strains and show independent strain-specific differences in bet-hedging and behavioral drift. We show manipulation of serotonin changes the rate of behavioral drift, indicating a potential circuit substrate controlling behavioral drift. We then develop a theoretical framework for assessing the adaptive value of phenotypic drift, demonstrating that drift may be adaptive for populations subject to selection pressures that fluctuate on timescales similar to the lifespan of an animal. We apply our model to real-world environmental signals and find patterns of fluctuations that favor random drift in behavioral phenotype, suggesting that drift may be adaptive under some real-world conditions. These results demonstrate that behavioral drift plays a role in driving variability in a population and may serve an adaptive role distinct from population level bet-hedging. Significance StatementWhy do individuals animals spontaneously change their preferences over time? While stable idiosyncratic behavioral preferences have been proposed to help species survive unpredictable environments as part of a bet-hedging strategy, the role of intraindividual shifts in preferences is unclear. Using Drosophila melanogaster, we show the stability of individual preferences is influenced by genetic background and neuromodulation, and is therefore a regulated phenomenon. We use theoretical modeling to show that shifts in preferences may be adaptive to environments that change within an individuals lifespan, including many real-world patterns of environmental fluctuations. Together, this work suggests that the stability of individual preferences may affect the survival of species in unpredictable worlds -- understanding that may be increasingly important in the face of anthropogenic change.

neuroscience↗

bioRxiv2024

Spatiotemporal dynamics of locomotor decisions in Drosophila melanogaster

Decision-making in animals often involves choosing actions while navigating the environment, a process markedly different from static decision paradigms commonly studied in laboratory settings. Even in decision-making assays in which animals can freely locomote, decision outcomes are often interpreted as happening at single points in space and single moments in time, a simplification that potentially glosses over important spatiotemporal dynamics. We investigated locomotor decision-making in Drosophila melanogaster in Y-shaped mazes, measuring the extent to which their future choices could be predicted through space and time. We demonstrate that turn-decisions can be reliably predicted from flies locomotor dynamics, with distinct predictability phases emerging as flies progress through maze regions. We show that these predictability dynamics are not merely the result of maze geometry or wall-following tendencies, but instead reflect the capacity of flies to move in ways that depend on sustained locomotor signatures, suggesting an active, working memory-like process. Additionally, we demonstrate that fly mutants known to have sensory and information-processing deficits exhibit altered spatial predictability patterns, highlighting the role of visual, mechanosensory, and dopaminergic signaling in locomotor decision-making. Finally, highlighting the broad applicability of our analyses, we generalize our findings to other species and tasks. We show that human participants in a virtual Y-maze exhibited similar decision predictability dynamics as flies. This study advances our understanding of decision-making processes, emphasizing the importance of spatial and temporal dynamics of locomotor behavior in the lead-up to discrete choice outcomes.

animal behavior and cognition↗

bioRxiv2020

Small-molecule inhibition of Lats kinases promotes Yap-dependent proliferation in postmitotic mammalian tissues

Hippo signaling is an evolutionarily conserved pathway that restricts organ growth during development and suppresses regeneration in mature organs1-3. Using a high-throughput phenotypic screen, we have identified a potent, non-toxic, and reversible inhibitor of Hippo signaling. An ATP-competitive inhibitor of Lats kinases, the compound causes Yap-dependent proliferation of murine supporting cells in the inner ear, murine cardiomyocytes, and human Muller glia in retinal organoids. RNA sequencing indicates that the substance fosters both the G1-S and G2-M checkpoint transitions and yields supporting cells capable of transdifferentiation. Upon withdrawal of the compound, a subset of supporting cells move their nuclei into the hair-cell layer and express genes characteristic of hair cells. Viral transfection of Atoh1 induces the expression of hair cellspecific proteins in progeny. The compound promotes the initial stages of the proliferative regeneration of hair cells, a process thought to be permanently suppressed in the adult mammalian inner ear.

developmental biology↗

bioRxiv2017

MAPLE: a Modular Automated Platform for Large-scale Experiments, a low-cost robot for integrated animal-handling and phenotyping

Genetic model system animals have significant scientific value in part because of large-scale experiments like screens, but performing such experiments over long time periods by hand is arduous and risks errors. Thus the field is poised to benefit from automation, just as molecular biology did from liquid-handling robots. We developed a Modular Automated Platform for Large-scale Experiments (MAPLE), a Drosophila-handling robot capable of conducting lab tasks and experiments. We demonstrate MAPLEs ability to accelerate the collection of virgin female flies (a pervasive experimental chore in fly genetics) and assist high-throughput phenotyping assays. Using MAPLE to autonomously run a novel social interaction experiment, we found that 1) pairs of flies exhibit persistent idiosyncrasies in affiliative behavior, 2) these dyad-specific interactions require olfactory and visual cues, and 3) social interaction network structure is topologically stable over time. These diverse examples demonstrate MAPLEs versatility as a general platform for conducting fly science automatically.

bioengineering↗