EPSRC logo

Details of Grant 

EPSRC Reference: EP/L027631/1
Title: Combined light sheet and scanning ion conductance microscopy : a new tool to perform single molecule biology in live cells
Principal Investigator: Klenerman, Professor D
Other Investigators:
Lee, Professor SF
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of Cambridge
Scheme: Standard Research
Starts: 01 December 2014 Ends: 30 November 2017 Value (£): 367,227
EPSRC Research Topic Classifications:
Biophysics Instrumentation Eng. & Dev.
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
23 Jul 2014 EPSRC Physical Sciences Physics - July 2014 Announced
Summary on Grant Application Form
A cell has many different molecules that interact which each other to respond to external signals and carry out functions that are essential for life and in many diseases these processes go awry. Techniques have recently been developed that allow one to follow individual molecules, so that one can directly watch molecules perform their function in live cells.

The aim of this proposal is to make a major advance in the types of biological processes that it is possible to follow. We will exploit a method that we have developed to deliver (down to) a single molecule to a defined location on the cell surface or within a cell, track the spatial position of that molecule and then any subsequent changes in the cell behaviour with time. Our method is based on a nanopipette, which is less than 100 nm in diameter, to deliver the molecules to the cell and we plan to generate a thin sheet of light to then image where these molecules go, recording a video of their fluorescence. Since we can synchronise when we deliver the molecules with when the light sheet is turned on, we can make the same measurements repetitively while minimally perturbing the cell. The idea is to use the cell as a 'test tube' to perform these types of experiments and automate the measurements so we can study many cells.

The project will start by adapting our existing instrument, building the light sheet illumination and then writing software to control the measurements. We will then perform a series of proof-of-concept experiments to optimise the instrument and method of making measurements. This will be used to stain a small number of molecules on the cell surface, trigger a key receptor associated with the immune response and then add damaging aggregates of the protein alpha synuclein into cells. This new method should then be applicable to a wide range of important biological and biomedical problems since in many cases one or a few molecules can perform key functions or cause disease. There are also many fundamental biological processes that take place in mammalian cells such as the copying and repairing of DNA that could then be studied using this new method in future work.
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.cam.ac.uk