Laser to give key insight into cell behaviour in nature

A laser instrument capable of hitting a sample a hundred thousand times a second is expected to provide scientists with vital information about the UV light-induced DNA damage that drives skin cancer. It will also uncover intricate detail about enzyme function in cells.

A grant announced by the Biotechnology and Biological Sciences Research Council (BBSRC) is paying for the LIFEtime instrument in STFC’s Central Laser Facility (CLF) at the Research Complex at Harwell. It will characterise photosynthesis in plants and changes in biologically important molecules, such as proteins and DNA. A second grant, giving a total of £1.5 million funding, will pay for a super-resolution microscope for the CLF, which can be used to study almost any organelle, or sub-unit within a cell, to see how it is functioning.

Looking at the inner workings of cells and proteins and characterising the very subtle changes taking place within them, is fundamental to understanding diseases such as cancer and to finding out how plants can develop resistance to attack from bacteria that can otherwise destroy them. Using lasers is one way to examine them with this level of detail.

The more scientists can understand interactions at the molecular level, the more they will be able to understand how different medicines will interact with proteins in the body with a view to more effective treatments being developed.

The LIFEtime instrument on the Central Laser Facility’s ULTRA facility will use ultrafast lasers to record on the same instrument, at the same time, both fast and slow measurements of changes taking place within a sample so that they can be compared in a reliable way. Looking at a sample over different timescales, from the very fast initial reaction that occurs when a laser hits the sample (less than one million millionth of a second) all the way to the ‘slower’ (milliseconds to seconds) follow-on reaction happening in the aftermath, can reveal processes that would otherwise be undetectable. These processes could uncover crucial information about how bacteria and plants respond to light and how DNA is damaged.

Professor Mike Towrie from the Central Laser Facility, said: “Sometimes experiments have to be repeated to gather information at both fast and slow timescales and there is always the risk of irreversible damage to precious or sensitive samples. For something as delicate as a short DNA base or protein that is already being hit a hundred thousand times a second - which is necessary with some samples - you want to limit potential damage as much as possible. LIFEtime will enable reactions across both fast and slow timescales to be measured at the same time, saving time, money and of course the precious samples”.

The other technology being funded by BBSRC is a new super-resolution microscope for a complex set up of lasers and microscopes, also unique in the world, which is called OCTOPUS because of its eight microscope ‘arms’. The new microscope will enable scientists to study in real time, almost any organelle, or sub-unit within a cell to see how it is functioning using ‘stimulated emission depletion microscopy’ where individual cells are lit up with lasers so that their interactions can be studied.

Gathering information for developing ‘nerve guidance conduits’ (NGC) which are used to bridge the gap in nerve injuries where the damage is so severe that nerves are not growing back is one way in which the microscope will be used. The new microscope will enable scientists to image at high resolution the interaction between the NGC and the nerve cells to optimise its structure and chemistry to produce more effective ‘bridges’.

Another area of work will be to monitor the behaviour of receptor molecules in plants as they respond to bacteria attacks to gain knowledge on how plants can be developed that would be more resistant to attack, reducing the requirement for pesticides.

Work looking at the interactions of special frameworks or ‘scaffolds’ with cells, which are being used to re-generate tissue and repair bone in an ageing population, will also be possible as a result of the grant.

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