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Targeted pain therapy

Pain is largely mediated through protein receptors on cell surfaces. The EU and United States have collaborated to investigate in detail the structure of a pain receptor for targeted pain therapy.
Targeted pain therapy
Cells are like small water balloons, having a phospholipid bilayer membrane that separates the intracellular from the extracellular fluid. The situation is dynamic partly due to proteins that span the membrane and create tiny channels that open or close in response to certain stimuli. This allows ions to diffuse down their concentration gradients producing signals important to biological functions.

One group of such proteins is the transient receptor potential (TRP) channel family, members of which are likely to play a role in the sensation of pain. Of particular interest is the three-dimensional (3D) structure of TRPV2, a pain receptor (nociceptor). TRPV2 responds to pressure, noxious heat and a compound in cannabis (cannabidiol) and could be an important pathway for novel acute and chronic pain treatments.

The EU-funded project PAIN_TRPV2 is a Marie Curie International Outgoing Fellowship (IOF) for characterising TRPV2 structure using the sophisticated single-particle cryo-electron microscopy technique. Experienced European researcher Dr Alex Perálvarez-Marín joined forces with the lab of Dr Montserrat Samsó in the United States. This move enabled knowledge and expertise transfer from the United States outgoing host to the Spanish return host institute.

Dr Perálvarez-Marín received training in multidisciplinary fields including the neurosciences, structural biology, computational methods and biotechnology. Together the team achieved major breakthroughs in the expression and purification of eukaryotic membrane proteins for subsequent structural characterisation at all levels of resolution. Such tools are indispensable for the knowledge-based design of drugs for diseases associated with dysfunction of protein receptors, channels and transporters. Transporters actively move substances into or out of the cell against their concentration gradients.

The project thus afforded the opportunity to bring back important expertise in structural biology to strengthen the programme at the recently created Centre d'Estudis en Biofísica in the Department of Biochemistry and Molecular Biology at the Universitat Autònoma de Barcelona.

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