China Partnering Award: Emerging Approaches to Intracellular Signaling
Lead Research Organisation:
University of Leeds
Department Name: Sch of Biomedical Sciences
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
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
Liu Y
(2019)
Volume-regulated Cl- current: contributions of distinct Cl- channels and localized Ca2+ signals.
in American journal of physiology. Cell physiology
Shah S
(2020)
Local Ca2+ signals couple activation of TRPV1 and ANO1 sensory ion channels.
in Science signaling
Tsai YM
(2020)
Vascular Kv7 channels control intracellular Ca2+ dynamics in smooth muscle.
in Cell calcium
Huang D
(2020)
Delineating an extracellular redox-sensitive module in T-type Ca2+ channels.
in The Journal of biological chemistry
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
Hurley ME
(2021)
A correlative super-resolution protocol to visualise structural underpinnings of fast second-messenger signalling in primary cell types.
in Methods (San Diego, Calif.)
Hogea A
(2021)
Junctophilin-4 facilitates inflammatory signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons.
in The Journal of physiology
| 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 up until re-opening of China international travel in Spring 2023. We obtained a no-cost extension of this grant until June 2024 and now we have successfully re-started the visits. Currently two visitors from China are on secondment in Leeds (February - May 2024) and two visitors from Leeds will go to China with 1-month visits in April 2024. 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. We also investigated regulation and modulation of multipipe other ion channels, including Kv7 (eLife 2022, J Biol Chem. 2023), T-type Ca2+ channels (J Biol Chem. 2020) and TRPV1 (Cell Rep 2022). Most importantly, the award allowed to establish a firm collaboration between the teams at the University of Leeds and Hebei Medical University. |
| Exploitation Route | The visiting scheme worked excellently before the lockdown and formed a foundation to further collaborations. However, due to covid-related travel restrictions which continued in China up until early sprig 2023, there was a extensive gap in the visiting activity. It was in part replaced by online interaction but this was not a fully adequate substitution. The visits resumed towards the second half of 2024, thanks to the no-cost extension. |
| Sectors | Education Pharmaceuticals and Medical Biotechnology |
| Description | CRACing inflammatory pain: investigating inflammatory store-operated Ca2+ entry in peripheral sensory axons |
| Amount | £613,618 (GBP) |
| Funding ID | APP37360 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2025 |
| End | 06/2028 |
| 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 | 06/2021 |
| 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. |