Biophysical and molecular characterisation of ORAI channel properties in skin-derived human cell lines
Lead Research Organisation:
University of Liverpool
Department Name: Institute of Integrative Biology
Abstract
The mechanism of store operated calcium entry (SOCE) in non-excitable tissues was first shown to be facilitated by the proteins STIM and Orai in 2006. This mechanism is now known to be key to controlling a variety of functions in a wide range of tissues, and especially for its role in regulating the immune and central nervous systems. More recently, STIM and Orai have been shown to mediate intracellular Ca2+ signalling in skin keratinocytes and cells from a variety of skin appendages.
The objective of this proposal is to use a multi-disciplinary approach to characterise the biophysical and molecular behaviour of Orai channel isoforms expressed in a selection of skin-derived cell lines. Methodologies will include cell culture, patch clamp electrophysiology, and bioinformatics / computational biology. The work will occur at three sites: the Institute of Integrative Biology, University of Liverpool, the Hartree Centre, STFC Daresbury, and Unilever Research & Development, Port Sunlight. The objective of the project is to provide the first detailed biophysical characterisation of the kinetic behaviour and modulatory potential of the Orai channel in the context of skin cell behaviour.
The project will allow the student to:
1. Derive their own biological questions, and explore these both experimentally and via state-of-the art in silico computer modelling
2. Master cutting-edge patch clamp electrophysiology techniques for measuring specific ion channel activities
3. Understand the nature of academic:industrial collaborations and industrially-relevant research questions
The objective of this proposal is to use a multi-disciplinary approach to characterise the biophysical and molecular behaviour of Orai channel isoforms expressed in a selection of skin-derived cell lines. Methodologies will include cell culture, patch clamp electrophysiology, and bioinformatics / computational biology. The work will occur at three sites: the Institute of Integrative Biology, University of Liverpool, the Hartree Centre, STFC Daresbury, and Unilever Research & Development, Port Sunlight. The objective of the project is to provide the first detailed biophysical characterisation of the kinetic behaviour and modulatory potential of the Orai channel in the context of skin cell behaviour.
The project will allow the student to:
1. Derive their own biological questions, and explore these both experimentally and via state-of-the art in silico computer modelling
2. Master cutting-edge patch clamp electrophysiology techniques for measuring specific ion channel activities
3. Understand the nature of academic:industrial collaborations and industrially-relevant research questions
Publications
Celik N
(2020)
Deep-Channel uses deep neural networks to detect single-molecule events from patch-clamp data.
in Communications biology
Manning D
(2023)
TRPC1 channel clustering during store-operated Ca2+ entry in keratinocytes.
in Frontiers in physiology
Manning D
(2022)
Store-operated calcium channels in skin
in Frontiers in Physiology
Manning D
(2020)
Calcium Store-Operated Currents in Human Skin Cells
in Biophysical Journal
Parker T
(2019)
Soluble adenylyl cyclase links Ca2+ entry to Ca2+/cAMP-response element binding protein (CREB) activation in vascular smooth muscle.
in Scientific reports