Open Postdoctoral position, faculty mentor Edward Bertaccini – Stanford University, United States

The Bertaccini Lab within the Stanford Department of Anesthesiology seeks an individual at the postdoctoral level with interest and expertise in molecular modeling related to protein homology modeling, ligand docking and drug design to develop the next generation of safer anesthetics. Specifically, this individual will initially be an integral developer of a large series of homology models of GABA receptors composed of variations in the available subunits. These models will be used to dock the few ligands available which are currently known to have GABAAR-slow subtype specificity in an effort to identify which subunits may characterize this feature. The most favorably interacting models will be tested in vitro, and then utilized for the subsequent phases of drug design, testing. Drug design will also involve molecular modeling methodologies to include but not limited to high throughput receptor-based screening, fragment-based design and modification, toxicity and bioavailability predictions. We have licenses for the full complement of Schrodinger and Discovery Studio Software packages.

As part of our overall endeavor, lead compounds will be subsequently subject to in vitro patch clamp affinity analyses and characterizations of the slow functional subtype with hippocampal brain slice electrophysiology. We will further characterize the compounds’ effects on in vitro iPSC-derived cardiomyocytes as a prediction of hemodynamic stability, and the effect on mitochondrial oxygen consumption and free radical production for prediction of potential tissue preservation. We will create formulations of our lead compounds and characterize their in vivo effects on levels of consciousness, response to painful stimuli and the standard battery of physiologic vital functions in rats after both intravenous (IV) and intramuscular (IM) injection. The resulting drug should allow immediate transition into more advanced drug pipelines which could include formal dose finding and PK/PD studies as well as higher mammalian models for eventual GLP and Pre-IND studies. This will work have vast implications in both the civilian realm (trauma, extremes of age, critically ill, etc) as well as the military realm (battlefield trauma, long term space flight, antidotes to chemical weapons, etc.). If interested please feel free to contact Professor Ed Bertaccini at edwardb@stanford.edu