Using light to weigh membrane proteins in lipid bilayers
Lead Research Organisation:
Aston University
Department Name: College of Health and Life Sciences
Abstract
Membrane proteins have large exposed hydrophobic domains for stability within the cell membrane. Solubilisation and purification of these proteins, whilst retaining correct structure and activity, is made complex by this conserved structure. A native or realistic lipid environment is particularly important, as lipid composition surrounding membrane proteins has been shown to greatly affect their structure and activity. Membrane proteins make up a large portion of therapeutic drug targets and are an important area of study for pharmaceutical research. It is of high interest to further develop reliable techniques for measuring activity and investigating structure.
Recently, lipid-disc forming copolymers (such as styrene maleic acid) have been used successfully to solubilise, purify and characterise a variety of membrane proteins. Styrene maleic acid (SMA) forms styrene maleic acid lipid particles (SMALPs) in the presence of biological membranes. Formation of these SMALP nano-discs can encapsulate membrane proteins present in these membranes and retain a native annulus of lipid around the protein, meaning SMA provides some advantages over traditional detergent solubilisation methods.
Refeyn have recently developed mass photometry as an analytical technique to measure the mass of singular molecules in solution without prior molecule labelling. This opens many pathways of research for the behavioural characterisation of molecule structure and dynamics in a native state.
This project aims to optimise the solubilisation and purification of target membrane proteins using lipid-disc forming copolymers or traditional detergent methods. Following this, mass photometry will be optimised as a technique to characterise and measure protein-protein interactions of these target membrane proteins in a native state. This research has the potential to provide a detailed characterisation of membrane protein interaction mechanisms and give insights into new or current drug targets.
Recently, lipid-disc forming copolymers (such as styrene maleic acid) have been used successfully to solubilise, purify and characterise a variety of membrane proteins. Styrene maleic acid (SMA) forms styrene maleic acid lipid particles (SMALPs) in the presence of biological membranes. Formation of these SMALP nano-discs can encapsulate membrane proteins present in these membranes and retain a native annulus of lipid around the protein, meaning SMA provides some advantages over traditional detergent solubilisation methods.
Refeyn have recently developed mass photometry as an analytical technique to measure the mass of singular molecules in solution without prior molecule labelling. This opens many pathways of research for the behavioural characterisation of molecule structure and dynamics in a native state.
This project aims to optimise the solubilisation and purification of target membrane proteins using lipid-disc forming copolymers or traditional detergent methods. Following this, mass photometry will be optimised as a technique to characterise and measure protein-protein interactions of these target membrane proteins in a native state. This research has the potential to provide a detailed characterisation of membrane protein interaction mechanisms and give insights into new or current drug targets.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/T00746X/1 | 01/10/2020 | 30/09/2028 | |||
| 2596861 | Studentship | BB/T00746X/1 | 01/10/2021 | 30/09/2025 | Caolan Browne |