Microscope system could lead to better cancer treatment

A groundbreaking microscope and laser system has helped scientists to make an important advance in research to improve cancer treatment.

A team from the Science and Technology Facilities Council (STFC) used the equipment to determine the structure of protein molecules in the body that can cause cancer if they stop working properly.

The facility, known as Octopus (Optics Clustered to Output Unique Solutions), allowed the researchers to examine the molecules while they were still in living cells, which could lead to the development of better cancer drugs.

Previously, scientists have used X-rays to examine the structure of such molecules, but to do this they used a purified, crystallised version of the protein, instead of the soluble form it takes when inside the body.

The structure identified from the crystallised molecule did not match with what was known about how the protein worked. Studying the molecule within a cell enabled the STFC team to see its natural shape.

‘We are trying to look at what happens in reality so we can see what the molecules do when put in a drug,’ said Dr Marisa Martin-Fernandez, project leader at the STFC’s Central Laser Facility (CLF) in Harwell, Oxfordshire.

‘Instead of having to make a hypothesis, we can infer from how they move in as close to normal conditions as possible what happens when we interfere.’

Octopus consists of a central hub that feeds laser beams via fibre optics to a cluster of seven microscopes surrounding it.

These enabled the team to use different imaging techniques, as well as chemical research, to piece together information about the molecules’ structure.

For example, one microscope enabled the scientists to study how different proteins interact with each other by using a laser to effectively label them with different colours. Another allowed the team to work out how the molecules were oriented.

‘Each microscope of the seven we have at the moment specialises in looking at a particular aspect of the problem,’ said Martin-Fernandez. ‘One single microscope cannot do it all because every one requires enormous specialisation.’

The molecules are known as epidermal growth-factor receptors (EGFRs) and act like antennas for living cells, receiving chemical signals from other cells that tell them, among other things, when to grow and divide.

Mutations that stop the EGFRs from working properly can lead to uncontrolled cell division, which causes a tumour to grow.

Some existing cancer drugs are used to block all the signals passed on by the EGFRs, halting tumour growth. But when this happens, the body can find ways of bypassing the signal system, allowing cancerous cells to grow again.

By better understanding the structure of EGFRs, scientists may be able to develop more targeted drugs that just block the part of the molecule telling the cells to grow without stopping all the signals.

Having identified the structure of one protein, the STFC team now plans to examine the other three commonly found in humans.