Biology subjects

Murray, S.

Publications and source records attributed to Murray, S..

3 recordsLinked to original sources

bioRxiv2018

A system for gene expression noise control in yeast

Gene expression noise arises from stochastic variation in the synthesis and degradation of mRNA and protein molecules and creates differences in protein numbers across populations of genetically identical cells. Such variability can lead to imprecision and reduced performance of both native and synthetic networks. In principle, gene expression noise can be controlled through the rates of transcription, translation and degradation, such that different combinations of those rates lead to the same protein concentrations but at different noise levels. Here, we present a \"noise tuner\" which allows orthogonal control over the transcription and the mRNA degradation rates by two different inducer molecules. Combining experiments with theoretical analysis, we show that in this system the noise is largely determined by the transcription rate whereas mean expression can be independently adjusted by mRNA stability. This noise tuner enables twofold changes in gene expression noise over a fivefold range of mean protein levels. We demonstrated the efficacy of the noise tuner in a complex regulatory network by varying gene expression noise in the mating pathway of Saccharomyces cerevisiae, which allowed us to control the output noise and the mutual information transduced through the pathway. The noise tuner thus represents an effective tool of gene expression noise control, both to interrogate noise sensitivity of natural networks and enhance performance of synthetic circuits.

synthetic biology↗

bioRxiv2018

Disrupted neural adaptation in autism spectrum disorder

There has been long-standing speculation that autism spectrum disorder (ASD) involves an increase in excitation relative to inhibition. However, there is little direct evidence of increased neural excitation in humans with ASD. Here we provide a potential explanation for this discrepancy: we show that increased neural excitation emerges only after repeated stimulation, manifesting as a deficit in neural adaptation. We measured fMRI responses induced by repeated audio-visual stimulation and button presses in early sensory-motor cortical areas. Across all cortical areas we show reduced adaptation in individuals with ASD compared to neurotypical individuals. The degree of adaptation is correlated between cortical areas and with button-press reaction times across subjects. These findings suggest that increased neural excitation in ASD, manifesting as dysregulated neural adaptation, is domain-general and behaviorally-relevant.

neuroscience↗

bioRxiv2017

Suppression and facilitation of human neural responses

Efficient neural processing depends on regulating responses through suppression and facilitation of neural activity. Utilizing a well-known visual motion paradigm that evokes behavioral suppression and facilitation, and combining 5 different methodologies (behavioral psychophysics, computational modeling, functional MRI, pharmacology, and magnetic resonance spectroscopy), we provide evidence that challenges commonly held assumptions about the neural processes underlying suppression and facilitation. We show that: 1) both suppression and facilitation can emerge from a single, computational principle - divisive normalization; there is no need to invoke separate neural mechanisms, 2) neural suppression and facilitation in the motion-selective area MT mirror perception, but strong suppression also occurs in earlier visual areas, and 3) suppression is not driven by GABA-mediated inhibition. Thus, while commonly used spatial suppression paradigms may provide insight into neural response magnitudes in visual areas, they cannot be used to infer neural inhibition.

neuroscience↗