PhD Discussion Sessions: Silvia Pittolo and Noelia Campillo

Alloswitch: an allosteric modulator for the control of a G protein-coupled receptor with light

Controlling drug activity with light offers the possibility of enhancing pharmacological selectivity with spatial and temporal regulation, thus enabling highly localized therapeutic effects and precise dosing patterns. We have developed and characterized what is to our knowledge the first photoswitchable allosteric modulator of a G protein–coupled receptor. Alloswitch-1 is selective for the metabotropic glutamate receptor mGlu5 and enables the optical control of endogenous mGlu5 receptors.

Effect of cyclic hypoxia mimicking obstructive sleep apnea on the expression of hypoxia-inducible factor

Intermittent hypoxia (IH), the process whereby tissues are recurrently subjected to episodes of low oxygen tension, is commonly associated with several pathological conditions, such as obstructive sleep apnea (OSA) or cancer. Increasing evidence suggests that the cyclic frequency of IH is directly related to the emergence of OSA-associated morbidities. Although HIF-1 has been identified as the critical factor regulating cell responses to hypoxia, the molecular mechanisms supporting the pathological effects of IH remain poorly understood. This is partly due to the lack of experimental systems to study the in vitro consequences of IH patterns realistically mimicking OSA. Here we present a simple polydimethylsiloxane (PDMS) chip aimed to apply high-frequency IH patterns and cyclic stretch simulating OSA at the cell level. The device was used to study the effect of different IH frequencies on HIF-1 expression.

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