China Partnering Award: Emerging Approaches to Intracellular Signaling

Lead Research Organisation: University of Leeds
Department Name: Sch of Biomedical Sciences

Abstract

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Publications

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Gamper N (2022) Inferiority complex: why do sensory ion channels multimerize? in Biochemical Society Transactions

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Huang D (2020) Delineating an extracellular redox-sensitive module in T-type Ca2+ channels. in The Journal of biological chemistry

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Jones F (2021) Kv7 Channels and Excitability Disorders. in Handbook of experimental pharmacology

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Liu Y (2019) Volume-regulated Cl- current: contributions of distinct Cl- channels and localized Ca2+ signals. in American journal of physiology. Cell physiology

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Zhang F (2019) Transcriptional Regulation of Voltage-Gated Sodium Channels Contributes to GM-CSF-Induced Pain. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Zhang H (2020) Auxiliary subunits control biophysical properties and response to compound NS5806 of the Kv4 potassium channel complex. in FASEB journal : official publication of the Federation of American Societies for Experimental Biology

 
Description At the onset of the project we have made a good progress in identifying interactions between the ANO1-like protein TMC7 and TRPV1 in mammalian sensory neurons. However, after pandemics started, no further academic exchange was possible.

The collaboration that started with the onset of this award has resulted in investigation of the molecular composition of the Kv4 potassium channel complex. This work has been published in the FASEB Journal. Additionally, we characterised the role of Kv7.4 potassium channels in vascular inflammation and remodeling. These findings are now published in Free Radical Biology and Medicine.
Exploitation Route The visiting scheme worked excellently before the lockdown and formed a foundation to further collaborations. However, currently the short visit research exchange with China is not possible.
Sectors Education,Pharmaceuticals and Medical Biotechnology

 
Description Divide and rule: localised Ca2+ signalling in sensory neurons
Amount £567,770 (GBP)
Funding ID BB/V010344/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2021 
End 06/2024
 
Title A correlative super-resolution protocol to visualise structural underpinnings of fast second-messenger signalling in primary cell types 
Description A correlative imaging protocol which allows the ubiquitous intracellular second messenger, calcium (Ca2+), to be directly visualised against nanoscale patterns of the Ca2+ channels in primary cells. This is achieved by combining total internal reflection fluorescence (TIRF) imaging of the elementary Ca2+ signals, with the subsequent DNA-PAINT super-resolution imaging of the Ca2+ channels. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact Most super-resolution microscopy methods require fixed cells/tissue. Here we developed a correlative approach in which live signaling events recorded from the living cells can be matched to the nanoscale structural information obtained with super-resolution imaging. This will further the scope of super-resolution imaging. 
 
Title All-optical monitoring of chloride channel activity in living cells 
Description We developed a triple-wavelength fluorescent imaging approach to simultaneously perform halide-sensitive EYFP quenching (to measure Cl- channel activity) and ratiometric fura-2 Ca2+ imaging. The method can be used as a higher-throughput alternative to patch-clamp for studying Ca2+-activated Cl- channels. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact The publication is currently under revision.