A modified enzyme could light the way to better imaging of brain tumours. 

Ariane Söling from the Georg August University in Göttingen, Germany, and colleagues, in a collaboration with Bruce Branchini of Conneticut College, New London, US, have shown that light from Branchini's analogue of a firefly luciferase enzyme penetrates tissue more deeply than the unmodified version. 

Luciferases catalyse a light-emitting reaction and the resulting bioluminescence can be used to monitor biological processes in vivo, such as tumour growth or metastasis. 'We are working on malignant brain tumours,' says Söling. 'In vivo studies are relatively difficult to conduct using bioluminescence imaging, as skull reduces the bioluminescent light signal emitted from the tumour 100-fold.' Branchini's enzyme produces light at a slightly longer wavelength than the unmodified luciferase, and she suggests that it is this red-shift that allows the light to penetrate tissue more deeply. 'Red light is known to be less absorbed by tissue,' she explains. 

Fireflies use luciferase to create bioluminescence

'Red-shifted luciferase reporter proteins could greatly improve in vivo imaging in cancer research,' says Soling. 'New bioluminescent reporters will also allow simultaneous imaging of multiple molecular processes in vivo,' she adds, 'and may thus help to identify complex molecular interactions.' 

Nikolai Rainov is a senior consultant neurosurgeon at the Augsburg Clinic, Germany, and carries out academic research in experimental neuro-oncology - the study of tumours of the nervous system. He says the most important finding of the work is that the light emission of the red-shifted analogue in living animals was up to 3.5 times more efficient than that of its unmodified counterpart, even though the in vitro activity was only a fraction of the activity of the unmodified luciferase. 

He adds that 'one of the most interesting aspects of this luciferase is the profound change in the light emitting activity of the enzyme after substitution of a single nucleotide [in the DNA plasmid used to generate the luciferase]. This phenomenon is known with other proteins, but rarely demonstrated in such a highly visual way.'

Rachel Cooper

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