Home Department: Human Biology
Mentor: Brian Kobilka (Molecular & Cellular Physiology)

2020 Research Project: “Measuring the Conformational States and Dwell Time of the Mu-Opioid Receptor”

Drugs which target the opioid receptor for analgesic, or pain-relieving, effects can have side effects that include respiratory suppression. Analgesia occurs when the receptor couples to a protein in the cell called a G protein, and respiratory suppression occurs when the receptor couples to a protein called arrestin. Lorena will measure the conformational changes of the opioid receptor, hoping to determine which changes in the receptor lead to coupling to the G protein, and which changes lead to respiratory suppression. This will provide insight into molecular mechanisms for the action of opioid drugs.
 

2021 Research Project: “The Role of G Protein Conformational Changes in Receptor Mediated Signaling”

Opioids such as morphine activate a mu opioid receptor to mediate its pain-relieving effect. These effects results from the opioid activating the receptor and the receptor then in turns activates a G protein. To understand how this effect is mediated at the G protein, the Kobilka lab is using a biophysical approach called single-molecule FRET to measure the changes in the conformation of the G protein before, during and after engagement with the receptor. These changes are measured by assessing the amount of energy that is transferred between two probes labelled on the G protein. High transfer of energy implies the probes are closer and low transfers of energy imply the probes are further away. Using this as a measure, we can follow how the G protein is changing during interactions with the receptor.