Postdoctoral Research Associate (Gumpper Lab)

Vacancy ID: PDS004952

Position Summary/Description:

G-protein-coupled receptors (GPCRs) play an important role across many important physiological systems (i.e. taste, vision, cardiac function, and neurotransmission). We are interested in the molecular mechanisms responsible for the nuanced signaling paradigms of GPCRs and how they lead to vastly different biological outcomes. Gaining atomistic insights into receptor-ligand interactions will allow us to design novel therapeutic compounds and molecular probes (rationally or through computational approaches).

As a model system, we study psychedelics. These compounds exhibit a complex polypharmacology impacting the serotonin, dopamine, and adrenergic receptor systems. While we are interested in investigating all receptor systems that psychedelics impact, we primarily study the 5-HT2A and 5-HT2C receptors. We want to develop novel therapeutic approaches exploiting these systems to create safer and more effective compounds for pain relief and neuropsychiatric disorders.

To interrogate these systems, we utilize state-of-the-art technologies and techniques in molecular pharmacology, structural biology, and computational biophysics.

Molecular Pharmacology and Chemical Biology:

We use various biochemical/pharmacological techniques to quantify the downstream signaling pathways and interaction partners related to GPCR activation. Additionally, we are interested in fully characterizing psychedelic polypharmacology (both structurally and mechanistically) and utilizing those pathways to develop novel compounds that can be used to treat chronic pain, neuropsychiatric disorders, as well as substance use disorders.

Structural Biology:

We use cryo-electron microscopy to reveal the molecular interactions between a drug and its receptor. This provides useful information for probing specific atomistic mechanisms that drive downstream signaling patterns and yield important interactions for structure-based drug design.

In Silico Approaches:

We use the latest computational approaches (MD simulations, docking, pipeline development) to reveal mechanistic insights into the dynamics of ligands and their receptors. Additionally, we use the latest developments in AI and ML and apply them with our expertise in structural biology and biochemical characterization.

Education and Experience:

The successful candidate will be a highly motivated, independent, and creative scientist with demonstrated experience in protein purification and structure determination by cryo-electron microscopy. The ideal applicant will have a strong track record of solving challenging structural biology problems, along with the ability to design, execute, and interpret experiments with minimal supervision. They will be intellectually curious, collaborative, and eager to contribute to an interdisciplinary research environment spanning molecular pharmacology, structural biology, and computational biophysics. A driven candidate will bring strong problem-solving skills, scientific rigor, and enthusiasm for using mechanistic insights to advance the discovery of novel therapeutic compounds and molecular probes.