Postdoctoral Research Associate (Gumpper Lab)

UNC-Chapel Hill • Chapel Hill, NC

4d

About The Position

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.

Requirements

• Proficient in protein expression and cryo-EM.
• Proficient in molecular cloning and PCR.

Nice To Haves

• Working with mammalian cell culture.
• Highly motivated, independent, and creative scientist.
• Demonstrated experience in protein purification and structure determination by cryo-electron microscopy.
• Strong track record of solving challenging structural biology problems.
• Ability to design, execute, and interpret experiments with minimal supervision.
• Intellectually curious, collaborative, and eager to contribute to an interdisciplinary research environment spanning molecular pharmacology, structural biology, and computational biophysics.
• Strong problem-solving skills.
• Scientific rigor.
• Enthusiasm for using mechanistic insights to advance the discovery of novel therapeutic compounds and molecular probes.

Responsibilities

• Quantify downstream signaling pathways and interaction partners related to GPCR activation using biochemical/pharmacological techniques.
• Fully characterize psychedelic polypharmacology (both structurally and mechanistically).
• Develop novel compounds to treat chronic pain, neuropsychiatric disorders, and substance use disorders.
• Reveal molecular interactions between drugs and receptors using cryo-electron microscopy.
• Probe specific atomistic mechanisms that drive downstream signaling patterns.
• Utilize structure-based drug design.
• Reveal mechanistic insights into the dynamics of ligands and their receptors using computational approaches (MD simulations, docking, pipeline development).
• Apply AI and ML developments with expertise in structural biology and biochemical characterization.

What This Job Offers

• Job Type: Full-time
• Career Level: Entry Level
• Education Level: No Education Listed