14 March 2014

Live biosensors for medicine and pharmacology

Researchers from Australia and the UK, working under the guidance of Dr. Paul Timpson, have created a universal mouse model, each cell of which expresses a fluorescent "biosensor", which allows you to observe the diseased cells and drugs injected into the body in real time in three dimensions.

The biosensor is a single-molecule probe developed in 2002 by Japanese professor Miki Matsuda and known as Raichu-Rac. Despite its widespread use in research practice, the authors managed for the first time to create a genetically modified mouse, each cell of which would express Raichu-Rac without functional impairment. This model can be used to study any type of cancer by crossing it with other mouse models, which will limit the expression of Raichu-Rac to certain cells or tissues. It can also be easily adapted to study other diseases.

The biosensor reacts to the activation of the target molecule, which in this case is the Rac protein. This protein triggers the movement of cells of many types of cancer through the body. It acts as a kind of switch from an inactive state to an active one.

When Rac is activated, the biosensor reacts to a certain chemical signal and begins to emit a blue glow. If the Rac is inactive, the biosensor emits a yellow glow.


Diagram from an article in Cell Reports

Special imaging techniques allow you to observe the activation of Rac in any organ at any time or to track fluctuations in the activity of this protein in the "front" or "back" part of the cell moving through the body. This technology has been used to monitor changes in Rac activity in many organs in response to drug therapy.


Breast tumor: Blue regions show high Rac activity,
which indicates a high probability of its metastasis.

According to the authors, the technique allows real-time observation and registration of regions of a cell or organ in which Rac is activated and triggers the metastasis process. It provides an opportunity to see how, as a result of the drug's effect on the molecular target, certain regions of the tumor change color from blue to yellow. This may occur an hour or more after the use of the drug, and the observed effect may weaken quickly or slowly. Pharmaceutical manufacturers should be aware of these features, which will allow them to select more effective dosages and protocols for the use of medicines.

Article by Anna-Karin E. Johnsson et al. The Rac-FRET Mouse Reveals Tight Spatial Control of Rac Activity in Primary Cells and Tissues published in the journal Cell Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Garvan Institute of Medical Research:
A versatile mouse that can teach us about many diseases and drugs.

14.03.2014

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