Neural activity in awake organisms shows widespread, spatiotemporally diverse correlations with behavioural and physiological measurements1-4. We propose that this covariation reflects in part the structured, nonlinear dynamics of an underlying arousal-related process that organizes brain-wide and body-wide physiology on the timescale of seconds. By framing this interpretation within dynamical systems theory, we arrive at a surprising prediction: a single, scalar measurement of arousal (for example, pupil diameter) should suffice to reconstruct the continuous evolution of multidimensional, spatiotemporal measurements of large-scale brain physiology. Here, to test this hypothesis, we perform multimodal cortex-wide optical imaging5 and behavioural monitoring in awake mice. We demonstrate that the seconds-scale spatiotemporal dynamics of neuronal calcium, metabolism and brain blood oxygen can be accurately and parsimoniously modelled from a low-dimensional, nonlinear manifold reconstructed from a time delay embedding6,7 of pupil diameter. Extending this framework to behavioural and electrophysiological measurements from the Allen Brain Observatory8, we demonstrate the ability to integrate diverse experimental data into a unified generative model via mappings from a shared arousal manifold. Our results support the hypothesis9 that spontaneous, spatially structured fluctuations in brain-wide physiology on timescales of seconds-widely interpreted to reflect regionally specific neural communication10,11-are in large part expressions of a low-dimensional, organism-wide dynamical system. In turn, reframing arousal itself as a latent dynamical system offers a new perspective on fluctuations in brain, body and behaviour observed across modalities, contexts and scales.

Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in treating blood cancers, but CAR T cell dysfunction remains a common cause of treatment failure1. Here we present CELLFIE, a CRISPR screening platform for enhancing CAR T cells across multiple clinical objectives. We performed genome-wide screens in human primary CAR T cells, with readouts capturing key aspects of T cell biology, including proliferation, target cell recognition, activation, apoptosis and fratricide, and exhaustion. Screening hits were prioritized using a new in vivo CROP-seq2 method in a xenograft model of human leukaemia, establishing several gene knockouts that boost CAR T cell efficacy. Most notably, we discovered that RHOG knockout is a potent and unexpected CAR T cell enhancer, both individually and together with FAS knockout, which was validated across multiple in vivo models, CAR designs and sample donors, and in patient-derived cells. Demonstrating the versatility of the CELLFIE platform, we also conducted combinatorial CRISPR screens to identify synergistic gene pairs and saturation base-editing screens to characterize RHOG variants. In summary, we discovered, validated and biologically characterized CRISPR-boosted CAR T cells that outperform standard CAR T cells in widely used benchmarks, establishing a foundational resource for optimizing cell-based immunotherapies.