| EPSRC Reference: |
EP/Y002830/1 |
| Title: |
Sensing And Signalling Of Extracellular Ca2+ In The Islet Of Langerhans |
| Principal Investigator: |
Zhao, Dr J T J |
| Other Investigators: |
|
| Researcher Co-Investigators: |
|
| Project Partners: |
|
| Department: |
Mechanical Engineering |
| Organisation: |
University of Hull |
| Scheme: |
Standard Research - NR1 |
| Starts: |
01 April 2024 |
Ends: |
30 September 2025 |
Value (£): |
161,994
|
| EPSRC Research Topic Classifications: |
| Instrumentation Eng. & Dev. |
|
|
| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
|
|
| Related Grants: |
|
| Panel History: |
| Panel Date | Panel Name | Outcome |
|
24 May 2023
|
ECR International Collaboration Grants Panel 2
|
Announced
|
|
|
Summary on Grant Application Form |
This project aims to develop a new sensing platform to resolve a long-standing puzzle: how extracellular Ca2+ coordinates pancreatic islet beta-cells for pulsatile insulin secretion. The latter is key to maintain the blood glucose homeostasis.
Free ionic Ca2+ is now recognised as an indispensable messenger in mediating cellular activities in nearly every aspect of cellular life for almost all mammalian cells. Although the roles of intracellular Ca2+ in relation to different biological functions have been well characterised, insights into extracellular Ca2+ are constrained by the lack of appropriate sensing methodology capable of distinguishing the subtle changes of Ca2+ over the high basal level (e.g., micromolar scale variances in millimolar order baseline). For one sensor mainstream - fluorescent indicators, they are particularly limited by the background autofluorescence (due to the use of a shorter wavelength excitation, indicators themselves fluoresce with longer wavelength emissions even in the absence of ions of interest). To overcome this limit, the proposed research will introduce state-of-the-art upconversion luminescence, which features the capacity of converting 980 nm infrared light excitation into visible emissions, to combine with conventional fluorescent indicators. Such a hybrid sensor will represent the world-first one that enables characterising extracellular Ca2+ quantitatively.
The upconversion-synergised hybrid sensor will then be applied to address how extracellular Ca2+ participates in coordinating pulsatile insulin secretion from pancreatic islet beta-cells - a key metabolic process coupled to glucose metabolism. The advent of such a sensor, in conjunction with a bespoke microfluidic device, will provide an opportunity to quantify the link between extracellular Ca2+ and pulsatile insulin secretion in isolated islets from mice at different metabolic states (health, prediabetes and type 2 diabetes). These analyses will lead to fundamental knowledge gains which can improve the current understanding on the pathophysiology of type 2 diabetes and may suggest new therapeutic strategies for the management of this major chronic disorder, thereby benefiting people living with type 2 diabetes (in 2021, 4.9 million in the UK and 536.6 million worldwide).
|
|
Key Findings |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Potential use in non-academic contexts |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Impacts |
|
| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
|
| Date Materialised |
|
|
|
|
Sectors submitted by the Researcher |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
| Project URL: |
|
| Further Information: |
|
| Organisation Website: |
http://www.hull.ac.uk |