Dr. GPCR Podcast

About Dr. Alix A. J. Rouault

"My contribution to science began during the equivalent of U.S. masters training at the Université de Bretagne Occidentale (UBO; France). Under the leadership of Dr. Karine Pichavant, I contributed to the development of a drug to treat hypovolemic shock after severe hemorrhage. During this time, Dr. Olivier Mignen, the director of another research unit at the UBO recommended me to Dr. Julien Sebag, a researcher at the University of Iowa. I spent two years working with Dr. Sebag as an exchanged scholar while my student visa was in the work, during which time I thoroughly reviewed the literature on the melanocortin receptor accessory protein 2 (MRAP2), resulting in my first peer-reviewed publication in Biochimica et Biophysica Acta (BBA). I then undertook my first project where I demonstrated that MRAP2 regulates the signaling of multiple G protein-coupled receptors (GPCRs) through different structural regions. This project yielded my first, first author publication in BBA – Molecular Cell Research, and a book chapter for Neuromethods on a technique I adapted to measure the mitochondrial pyruvate oxidation in primary neurons.

In 2017 I officially joined the PhD program in the Department of Molecular Physiology and Biophysics at the University of Iowa Carver College of Medicine, under the mentorship of Dr. Sebag. During my PhD, I continued my studies on MRAP2. I contributed to an In-vivo project that showed that MRAP2 regulates the growth hormone secretagogue receptor-1a (GHSR1a), the results of which are published in Nature Communications. Concurrently, I described the mechanisms by which MRAP2 regulates GHSR1a signaling; this project brought forth our NanoBiT-based arrestin recruitment assay. At the time, NanoBiT was a prototype technology we gained access to by collaborating with Promega. This powerful tool allowed us to create an assay that kinetically measured the arrestin recruitment to an activated GPCR for the first time. Using this novel technique, I showed that MRAP2 biased GHSR1a signaling and shut down its constitutive activity; this work resulted in a first author publication in Science Signaling.

While writing my thesis, I published another paper in the Journal of Biological Chemistry which described the molecular mechanisms of MRAP2 regulation of the GHSR1a, and where I notably developed the C-terminal gate theory. This theory states that the post-translational modification of GHSR1a’ C-terminal tail is not a docking space for the arrestins, but rather a necessary modification leading to a structural change granting the arrestins access to the core of the receptor. Some of my data were also used in an In-vivo study published in iScience, showing the relevance of the MRAP2 regulatory effect on GHSR1a in pancreatic islets.

Dr. Cone’s lab was a clear choice for a postdoc. Dr. Cone was the first to clone the melanocortin receptors (the GPCRs that led to the discovery of MRAP2), and his lab works is highly In-vivo oriented. Since I joined the lab, I became proficient in many In-vivo techniques, I adapted my arrestin recruitment assay to a high throughput screening format for drug discovery, I have started molecular work on the melanocortin receptors. I also invested a tremendous amount of time in developing my leadership skills. I spent time running for the chair of International Affairs for the U-M Postdoctoral Association (UMPDA). Further, I applied to create a scientific session at the American Physiology Summit (APS) 2024 dedicated to GPCR biased signaling. Dr. Lauren Slosky and Dr. Joshua Gross were enthusiastic about the idea and jumped on board. Our session was picked up by the APS. We were pleasantly surprised by the interest generated by our scientific session, Dr. Michel Bouvier accepted to open our session and will be followed by Dr. John McCorvy, Dr. Dylan Eiger, and Joshua Gross. We are very excited about this event.

At this point in my career, I am creating connections with biomedical industry, assessing professional opportunities, and seriously weighing strengths of career options across sectors; however, academia does not make information about industry widely accessible to trainees. This is, in part, why I ran for, and was elected Chair of International Affairs of the University of Michigan Postdoc Association. I want to connect more trainees with diverse career resources to support professional decision-making. I am hopeful that my efforts to support the professional opportunities of my peers, in combination with my own scientific endeavors, will inform my future career decisions."

Dr. Alix A. J. Rouault on the web

• University of Michigan

• Carver College of Medicine

• ResearchGate

• Google Scholar

• Dr. GPCR