Most drugs work by binding to, and changing the function of, proteins in our bodies. However, there are many thousands of potential molecules that could be chosen to work with a given target protein – and a stressful situation can be just the thing to reveal the best candidate.

UCL biochemical engineers, working with London Centre for Nanotechnology researchers, have created a microfluidic device that can analyse tiny amounts – just billionths of a litre – of drugs and their targets, in channels less than a millimetre wide.

They successfully demonstrate that microfluidics and chemically induced stress could reveal how the drug rapamycin, an immune suppressant, interacts with the FKBP12 cell-signalling protein.

FKBP12 was mixed with a chemical that caused it to bend out of shape (denature), and passed through a microfluidic channel illuminated by a laser. Since the molecules react to the laser light differently depending on their shape, scientists were able to determine how the protein was deforming by looking at the light it gave back out. Repeating this with increasing concentrations of the chemical told them the exact concentration that would unfold the protein completely.

When the same technique was used on FKBP12 mixed with rapamycin, a higher concentration of denaturant was needed to unfold the cell-signalling protein – showing that the presence of rapamycin made the protein more stable. Comparing the results with and without the therapeutic molecules allowed the researchers to determine how tightly the drug was bound to the FKBP12 protein – a measure of how effective it is.

Quantifying how drugs bind to their protein targets is just one potential use of microfluidics – a technique which, thanks to its speed, affordability and the very small sample sizes required, has applications ranging from largescale drug discovery to healthcare diagnostics and pathogen detection.

Just one example of how research at UCL Biochemical Engineering could change the world.

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