Biology subjects

Wise, T.

Publications and source records attributed to Wise, T..

7 recordsLinked to original sources

bioRxiv2026

Split suppression gene drives reveal a design tradeoff between inheritance and reproductive load in Aedes aegypti

Mosquito-borne pathogens cause approximately 700,000 deaths annually, highlighting the need for effective and sustainable vector control strategies. CRISPR-based gene drives offer a potential approach for suppressing disease-vector populations, but autonomous drives may spread beyond intended populations. Split gene drives, in which the Cas9 and guide RNA components are genetically separated, provide an inherently confinable alternative because biased inheritance depends on the co-occurrence of both components. Here, we develop the first split suppression gene drives in Ae. aegypti, targeting the female reproductive genes doublesex (dsx) and yellow-g (yg). The yg-targeting drive exhibited moderate super-Mendelian inheritance, reaching 73.4% transmission in the highest-performing cross, whereas the dsx-targeting drive exhibited little detectable inheritance bias. Conversely, disruption of dsx imposed substantially stronger reproductive fitness costs, including complete sterility in homozygous females, whereas yg disruption produced a less severe fertility phenotype. Mathematical modeling parameterized with these experimental data predicted that three of four split-drive configurations could achieve population suppression at lower release intensities or shorter release durations than pgSIT across portions of the modeled parameter space. Together, these results reveal that inheritance efficiency and reproductive load can impose competing constraints on split suppression drive performance: stronger suppression-associated fitness effects do not necessarily translate into improved drive performance when accompanied by limited drive propagation. Our findings establish the feasibility of split suppression gene drives in Ae. aegypti and demonstrate that effective suppression drive design requires balancing inheritance efficiency with reproductive fitness costs rather than maximizing either independently.

bioengineering↗

bioRxiv2023

Incorporating uncertainty within dynamic interoceptive learning

Interoception, the perception of the internal state of the body, has been shown to be closely linked to emotions and mental health. Of particular interest are interoceptive learning processes that capture associations between environmental cues and body signals as a basis for making homeostatically relevant predictions about the future. Here we extended an interoceptive Breathing Learning Task (BLT) to incorporate continuous measures of prediction certainty, and tested its application using a Rescorla Wagner (RW) associative learning model. Sixteen healthy participants completed the continuous version of the BLT, where they were asked to predict the likelihood of breathing resistances. The task was modified from a previous version and required continuous, rather than binary predictions, in order to include a more precise measure of prediction certainty. The RW model was used to fit a learning rate to each participants continuous and binarised predictions, and was additionally extended to test whether learning rates differed according to stimuli valence. The empirical task data demonstrated excellent replicability compared to previously collected data using binary predictions, and the continuous model fits closely captured participant behaviour at the group level. The model extension to estimate different learning rates for negative (i.e. breathing resistance) and positive (i.e. no breathing resistance) trials indicated that learning rates did not significantly differ according to stimuli nature. Furthermore, examining the relationship between estimates of prediction certainty and learning rates with interoceptive and mental health questionnaires demonstrated that fatigue severity was related to both prediction certainty and learning rate, and anxiety sensitivity was related to prediction certainty. The updated task and model show promise for future investigations into interoceptive learning and potential links to mental health.

neuroscience↗

bioRxiv2021

Eliminating Mosquitoes with Precision Guided Sterile Males

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and eliminate mosquitoes in multigenerational population cages. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.

genetics↗

bioRxiv2020

Model-based aversive learning in humans is supported by preferential task state reactivation

Harm avoidance is critical for survival, yet little is known regarding the underlying neural mechanisms supporting avoidance when we cannot rely on direct trial and error experience. Neural reactivation, and sequential replay, have emerged as potential candidate mechanisms. Here, during an aversive learning task, in conjunction with magnetoencephalography, we show prospective and retrospective reactivation for planning and learning respectively, coupled to evidence for sequential replay. Specifically, when subjects plan in an aversive context, we find preferential reactivation of subsequently chosen goal states and sequential replay of the preceding path. This reactivation was associated with greater hippocampal theta power. At outcome receipt, unchosen goal states are reactivated regardless of outcome valence. However, replay of paths leading to goal states was directionally modulated by outcome valence, with aversive outcomes leading to stronger reverse replay compared to safe outcomes. Our findings suggest that avoidance behaviour involves simulation of alternative future and past outcome states through hippocampally-mediated reactivation and replay.

neuroscience↗

bioRxiv2020

Neural encoding of socially adjusted value during competitive and hazardous foraging

In group foraging organisms, optimizing the conflicting demands of competitive food loss and safety is critical. We demonstrate that humans select competition avoidant and risk diluting strategies during foraging depending on socially adjusted value. We formulate a mathematically grounded quantification of socially adjusted value in foraging environments and show using multivariate fMRI analyses that socially adjusted value is encoded by mid-cingulate and ventromedial prefrontal cortices, regions that integrate value and action signals.

neuroscience↗

bioRxiv2020

The Role of the Medial Prefrontal Cortex in Spatial Margin of Safety Calculations

Humans, like many other animals, pre-empt danger by moving to locations that maximize their success at escaping future threats. We test the idea that spatial margin of safety (MOS) decisions, a form of pre-emptive avoidance, results in participants placing themselves closer to safer locations when facing more unpredictable threats. Using multivariate pattern analysis on fMRI data collected while subjects engaged in MOS decisions with varying attack location predictability, we show that while the hippocampus encodes MOS decisions across all types of threat, a vmPFC anterior-posterior gradient tracked threat predictability. The posterior vmPFC encoded for more unpredictable threat and showed functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings suggest that when pre-empting danger, the anterior vmPFC may provide a safety signal, possibly via predictable positive outcomes, while the posterior vmPFC drives prospective danger signals.

neuroscience↗

bioRxiv2019

Associations between aversive learning processes and transdiagnostic psychiatric symptoms revealed by large-scale phenotyping

BackgroundSymptom expression in a range of psychiatric conditions is linked to altered threat perception, manifesting particularly in uncertain environments. How precise computational mechanisms that support aversive learning, and uncertainty estimation, relate to the presence of specific psychiatric symptoms remains undetermined. 400 subjects completed an online game-based aversive learning task, requiring avoidance of negative outcomes, in conjunction with completing measures of common psychiatric symptoms. We used a probabilistic computational model to measure distinct processes involved in learning, in addition to inferred estimates of safety likelihood and uncertainty, and tested for associations between these variables and traditional psychiatric constructs alongside transdiagnostic dimensions. We used partial least squares regression to identify components of psychopathology grounded in both aversive learning behaviour and symptom self-report. We show that state anxiety and a transdiagnostic compulsivity-related factor are associated with enhanced learning from safety, and data-driven analysis indicated the presence of two separable components across our behavioural and questionnaire data: one linked enhanced safety learning and lower estimated uncertainty to physiological anxiety, compulsivity, and impulsivity; the other linked enhanced threat learning, and heightened uncertainty estimation, to symptoms of depression and social anxiety. Our findings implicate distinct aversive learning processes in the expression of psychiatric symptoms that transcend traditional diagnostic boundaries.

neuroscience↗