New technique to speed up drug development

Scientists working at the European Molecular Biology Laboratory in Grenoble, France have developed a new technique that enables them to introduce up to 15 fluorescent markers to a mammalian cell in one go. They say their findings could help speed up drug development and screening.

The study was funded in part by the P-CUBE (‘Protein production platforms’) project, which has clinched EUR 6.6 million through the Research Infrastructures budget line of the EU’s Seventh Framework Programme (FP7).

EMBL’s Imre Berger previously developed a technique that allowed scientists to create the equivalent of a make-up brush that is applied only once and highlights different features simultaneously. So cells could be given fluorescent labels to mark various cellular components in different colours, for example blue for the nucleus, yellow for the tubulin (a component of the cell’s scaffolding), red for the mitochondria, cyan for the membranes of vesicles called endosomes, and purple for the other membrane structures. This technology was created by Dr Berger as part of a method called MultiBac and used for expressing protein complexes in insect cells.

In this latest study, published in the journal Nature Communications, Dr Berger and Philipp Berger from the Paul Scherrer Institut (PSI) in Villigen, Switzerland joined forces to take this technology a step further, adopting the concept to mammalian cells like our own for the first time. This essentially involved rapidly engineering a single vector to deliver a theoretically unlimited number of foreign genes, to a cell.

To date, the scientists have successfully delivered up to 15 genes in this way. The protein encoded by each of those genes can carry a fluorescent label, so this makes multiple labelling much more efficient than previous methods. The new labelling technique for mammalian cells, called MultiLabel, could help make drug development and screening considerably faster, since it allows scientists to precisely label many cellular components involved in a given disease process and follow them all at the same time.

‘The introduction of heterologous genetic information, particularly of multiple genes, into mammalian cells is a key technology in contemporary experimental biological research,’ the researchers said.

‘The co-expression of fluorescently tagged sensors is required to simultaneously analyse multiple parameters in living cells and the co-expression of several proteins is necessary to manipulate cell fate in stem cell biology. Current technologies for multigene expression in mammalian cells are inefficient, inflexible and time-consuming.’

The team explained that MultiLabel is ‘a novel and highly efficient modular plasmid-based eukaryotic expression system’.

The P-CUBE project aims to provide greater, free access for European users to the most advanced techniques in cloning, expression, protein characterisation and crystallisation. To this end, the British and Swiss-based scientists involved in the project regularly share expertise to improve technologies and standardise procedures, with the ultimate aim of disseminating this expertise throughout Europe.