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Article ; Online: Temperature-driven coordination of circadian transcriptional regulation.

Xu, Bingxian / Hwangbo, Dae-Sung / Saurabh, Sumit / Rosensweig, Clark / Allada, Ravi / Kath, William L / Braun, Rosemary

PLoS computational biology

2024 Volume 20, Issue 4, Page(s) e1012029

Abstract: The circadian clock is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce circadian oscillations in thousands of genes in a tissue- ... ...

Abstract	The circadian clock is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce circadian oscillations in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While previous studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood. By analyzing bulk-RNA sequencing of Drosophila fat bodies harvested from flies subjected to different environmental conditions, we demonstrate a highly condition-specific circadian transcriptome: genes are cycling in a temperature-specific manner, and the distributions of their phases also differ between the two conditions. Further employing a reference-based gene regulatory network (Reactome), we find evidence of increased gene-gene coordination at low temperatures and synchronization of rhythmic genes that are network neighbors. We report that the phase differences between cycling genes increase as a function of geodesic distance in the low temperature condition, suggesting increased coordination of cycling on the gene regulatory network. Our results suggest a potential mechanism whereby the circadian clock mediates the fly's response to seasonal changes in temperature.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1012029
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Temperature-driven coordination of circadian transcriptome regulation.

Xu, Bingxian / Hwangbo, Dae-Sung / Saurabh, Sumit / Rosensweig, Clark / Allada, Ravi / Kath, William L / Braun, Rosemary

bioRxiv : the preprint server for biology

2023

Abstract: The circadian rhythm is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce a circadian oscillation in thousands of genes in a tissue- ...

Abstract	The circadian rhythm is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce a circadian oscillation in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood. By analyzing bulk-RNA sequencing of
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.27.563979
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Book ; Online: Modeling Transient Changes in Circadian Rhythms

Zhao, Ziyu / Hwangbo, Dae-Sung / Saurabh, Sumit / Rosensweig, Clark / Allada, Ravi / Kath, William L. / Braun, Rosemary

2023

Abstract: The circadian clock can adapt itself to external cues, but the molecular mechanisms and regulatory networks governing circadian oscillations' transient adjustments are still largely unknown. Here we consider the specific case of circadian oscillations ... ...

Abstract	The circadian clock can adapt itself to external cues, but the molecular mechanisms and regulatory networks governing circadian oscillations' transient adjustments are still largely unknown. Here we consider the specific case of circadian oscillations transiently responding to a temperature change. Using a framework motivated by Floquet theory, we model the mRNA expression level of the fat body from Drosophila melanogaster following a step change from 25C to 18C. Using the method we infer the adaptation rates of individual genes as they adapt to the new temperature. To deal with heteroskedastic noise and outliers present in the expression data we employ quantile regression and wild bootstrap for significance testing. Model selection with finite-sample corrected Akaike Information Criterion (AICc) is performed additionally for robust inference. We identify several genes with fast transition rates as potential sources of temperature-mediated responses in the circadian system of fruit flies, and the constructed network suggests that the proteasome may play important roles in governing these responses.
Keywords	Quantitative Biology - Molecular Networks ; Quantitative Biology - Quantitative Methods
Subject code	612
Publishing date	2023-04-14
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Time-Series Data in Circadian Biology Research.

Ness-Cohn, Elan / Iwanaszko, Marta / Kath, William L / Allada, Ravi / Braun, Rosemary

Journal of biological rhythms

2020 Volume 35, Issue 5, Page(s) 439–451

Abstract: The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by ... ...

Abstract	The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms' performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.
MeSH term(s)	Algorithms ; Animals ; Chronobiology Discipline/methods ; Circadian Rhythm ; Gene Expression Profiling/methods ; Humans ; Mice ; Software ; Time Factors ; Transcriptome
Language	English
Publishing date	2020-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730420934672
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Article ; Online: Rapid threat assessment in the Drosophila thermosensory system.

Jouandet, Genevieve C / Alpert, Michael H / Simões, José Miguel / Suhendra, Richard / Frank, Dominic D / Levy, Joshua I / Para, Alessia / Kath, William L / Gallio, Marco

Nature communications

2023 Volume 14, Issue 1, Page(s) 7067

Abstract: Neurons that participate in sensory processing often display "ON" responses, i.e., fire transiently at the onset of a stimulus. ON transients are widespread, perhaps universal to sensory coding, yet their function is not always well-understood. Here, we ... ...

Abstract	Neurons that participate in sensory processing often display "ON" responses, i.e., fire transiently at the onset of a stimulus. ON transients are widespread, perhaps universal to sensory coding, yet their function is not always well-understood. Here, we show that ON responses in the Drosophila thermosensory system extrapolate the trajectory of temperature change, priming escape behavior if unsafe thermal conditions are imminent. First, we show that second-order thermosensory projection neurons (TPN-IIIs) and their Lateral Horn targets (TLHONs), display ON responses to thermal stimuli, independent of direction of change (heating or cooling) and of absolute temperature. Instead, they track the rate of temperature change, with TLHONs firing exclusively to rapid changes (>0.2 °C/s). Next, we use connectomics to track TLHONs' output to descending neurons that control walking and escape, and modeling and genetic silencing to demonstrate how ON transients can flexibly amplify aversive responses to small thermal change. Our results suggest that, across sensory systems, ON transients may represent a general mechanism to systematically anticipate and respond to salient or dangerous conditions.
MeSH term(s)	Animals ; Drosophila ; Neurons/physiology ; Sensation/physiology ; Temperature ; Cold Temperature
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42864-5
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Article: Computational modeling of dendrites.

Kath, William L

Journal of neurobiology

2005 Volume 64, Issue 1, Page(s) 91–99

Abstract: Computational methods have been part of neuroscience for many years. For example, models developed with these methods have provided a theory that helps explain the action potential. More recently, as experimental patch-electrode techniques have revealed ... ...

Abstract	Computational methods have been part of neuroscience for many years. For example, models developed with these methods have provided a theory that helps explain the action potential. More recently, as experimental patch-electrode techniques have revealed new biophysics related to dendritic function and synaptic integration, computational models of dendrites have been developed to explain and further illuminate these results, and to predict possible additional behavior. Here, a collection of computational models of dendrites is reviewed. The goal is to help explain how such computational techniques work, some of their limitations, and what one can hope to learn about dendrites by modeling them.
MeSH term(s)	Action Potentials/physiology ; Animals ; Computer Simulation ; Dendrites/physiology ; Electric Conductivity ; Models, Neurological ; Neurons/cytology ; Neurons/physiology ; Synapses/physiology
Language	English
Publishing date	2005-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	300903-8
ISSN	1097-4695 ; 0022-3034
ISSN (online)	1097-4695
ISSN	0022-3034
DOI	10.1002/neu.20154
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Article: Control of Stochastic and Induced Switching in Biophysical Networks.

Wells, Daniel K / Kath, William L / Motter, Adilson E

Physical review. X

2015 Volume 5

Abstract: Noise caused by fluctuations at the molecular level is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it to induce a ... ...

Abstract	Noise caused by fluctuations at the molecular level is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it to induce a desired cell state. Here we present a scalable, quantitative method based on the Freidlin-Wentzell action to predict and control noise-induced switching between different states in genetic networks that, conveniently, can also control transitions between stable states in the absence of noise. We apply this methodology to models of cell differentiation and show how predicted manipulations of tunable factors can induce lineage changes, and further utilize it to identify new candidate strategies for cancer therapy in a cell death pathway model. This framework offers a systems approach to identifying the key factors for rationally manipulating biophysical dynamics, and should also find use in controlling other classes of noisy complex networks.
Language	English
Publishing date	2015-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2622565-7
ISSN	2160-3308
ISSN	2160-3308
DOI	10.1103/PhysRevX.5.031036
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Article ; Online: Robustness and plasticity in Drosophila heat avoidance.

Simões, José Miguel / Levy, Joshua I / Zaharieva, Emanuela E / Vinson, Leah T / Zhao, Peixiong / Alpert, Michael H / Kath, William L / Para, Alessia / Gallio, Marco

Nature communications

2021 Volume 12, Issue 1, Page(s) 2044

Abstract: Simple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in Drosophila. First, we demonstrate that hot receptor neurons ... ...

Abstract	Simple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in Drosophila. First, we demonstrate that hot receptor neurons of the antenna and their molecular heat sensor, Gr28B.d, are essential for flies to produce escape turns away from heat. High-resolution fly tracking combined with a 3D simulation of the thermal environment shows that, in steep thermal gradients, the direction of escape turns is determined by minute temperature differences between the antennae (0.1°-1 °C). In parallel, live calcium imaging confirms that such small stimuli reliably activate both peripheral thermosensory neurons and central circuits. Next, based on our measurements, we evolve a fly/vehicle model with two symmetrical sensors and motors (a "Braitenberg vehicle") which closely approximates basic fly thermotaxis. Critical differences between real flies and the hard-wired vehicle reveal that fly heat avoidance involves decision-making, relies on rapid learning, and is robust to new conditions, features generally associated with more complex behavior.
MeSH term(s)	Animals ; Behavior, Animal ; Choice Behavior ; Drosophila melanogaster/genetics ; Drosophila melanogaster/physiology ; Imaging, Three-Dimensional ; Taxis Response/physiology ; Thermosensing/physiology
Language	English
Publishing date	2021-04-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22322-w
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Article ; Online: Realistic control of network dynamics.

Cornelius, Sean P / Kath, William L / Motter, Adilson E

Nature communications

2013 Volume 4, Page(s) 1942

Abstract: The control of complex networks is of paramount importance in areas as diverse as ecosystem management, emergency response and cell reprogramming. A fundamental property of networks is that perturbations to one node can affect other nodes, potentially ... ...

Abstract	The control of complex networks is of paramount importance in areas as diverse as ecosystem management, emergency response and cell reprogramming. A fundamental property of networks is that perturbations to one node can affect other nodes, potentially causing the entire system to change behaviour or fail. Here we show that it is possible to exploit the same principle to control network behaviour. Our approach accounts for the nonlinear dynamics inherent to real systems, and allows bringing the system to a desired target state even when this state is not directly accessible due to constraints that limit the allowed interventions. Applications show that this framework permits reprogramming a network to a desired task, as well as rescuing networks from the brink of failure-which we illustrate through the mitigation of cascading failures in a power-grid network and the identification of potential drug targets in a signalling network of human cancer.
MeSH term(s)	Cell Survival ; Humans ; Leukemia, Large Granular Lymphocytic/pathology ; Models, Biological ; Power Plants ; Signal Transduction ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology
Language	English
Publishing date	2013-06-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms2939
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Article ; Online: The E3 ubiquitin ligase adaptor

Lee, Jongbin / Lim, Chunghun / Han, Tae Hee / Andreani, Tomas / Moye, Matthew / Curran, Jack / Johnson, Eric / Kath, William L / Diekman, Casey O / Lear, Bridget C / Allada, Ravi

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 47

Abstract: Circadian transcriptional timekeepers in pacemaker neurons drive profound daily rhythms in sleep and wake. Here we reveal a molecular pathway that links core transcriptional oscillators to neuronal and behavioral rhythms. Using two independent genetic ... ...

Abstract	Circadian transcriptional timekeepers in pacemaker neurons drive profound daily rhythms in sleep and wake. Here we reveal a molecular pathway that links core transcriptional oscillators to neuronal and behavioral rhythms. Using two independent genetic screens, we identified mutants of
MeSH term(s)	Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator/genetics ; Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism ; Circadian Clocks/physiology ; Cullin Proteins/genetics ; Cullin Proteins/metabolism ; Drosophila ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Neurons/metabolism ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Proteomics ; Sleep ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Cul3 protein, Drosophila ; Cullin Proteins ; Drosophila Proteins ; Neuropeptides ; pdf protein, Drosophila ; tgo protein, Drosophila ; Aryl Hydrocarbon Receptor Nuclear Translocator (138391-32-9) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2110767118
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