Job Category Fulltime Regular
ExemptOvertime Eligible Exempt
Benefits Eligible Benefit Based
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The Senior Scientist will develop and perform research with ketamine, utilizing the already existing genetically encoded fluorescent biosensors methodology established and applied successfully for nicotine.
Proposed experiments will guide the development of ketamine and related molecules with fewer potential side effects as fast-acting therapies for depression. Understanding how this rapid antidepressant mechanism works holds promise for development of more robust and safer treatments in a clinical setting.
- Reengineer existing biosensor proteins already developed in lab to detect drugs, specifically ketamine and its derivatives within organelles and thereby develop a robust tool data for therapeutic strategies. The specific goal of the project would be to develop genetically encoded sensors of ketamine and related derivates and/or molecules to enable detection in various intracellular compartments. This would further enable us to probe the antidepressant and general mechanism of action of ketamine which is currently unknown.
- Development of genetically encoded fluorescent biosensors of ligands.
- Expression and fluorescent imaging in cultured mammalian cells.
- Isothermal titration calorimetry
- Stopped-flow analysis
- Candidate will author and coauthor results and findings and will present those findings via journals or conferences
- Candidate will often be required to work with a team in order to co-mentor other lab personnel for establishing directed evolution and biosensor engineering, and to provide technical training on specialized equipment
- PhD and at least 5 years of postdoctoral experience
- Experience in chemistry and extensive knowledge in molecular biology, tissue culture, protein engineering, fluorescence imaging, TIRF and confocal scanning microscopy, wide field imaging,operating robots, plate readers and other protein purification apparatus.
- Advanced molecular biology skills such as site-directed as well as site-saturated mutagenesis.
- An in-depth understanding of the principles behind directed evolution and protein engineering, design of novel peptide and biosensor based molecules to study complex biological questions in real time, and structure function relationship studies of macromolecules
- Experience in designing and implementing protein engineering experiments such as:
- Protein engineering: Directed evolution, rational protein design, mutant library generation, site directed and site saturated mutagenesis, protein production in E. coli, yeast, and mammalian cell lines, novel mutant library generation methods, synthetic gene design, gene deletion from E. coli, homologous recombination, spectroscopic and fluorometric assay development, enzyme/antibody/biosensor purification, isothermal titration calorimetry, yeast and bacterial surface display, X-ray crystallography, protein engineering in bacteria
- Peptide design and discovery: random peptide library screening using bacterial display and flow cytometry, cyclic peptide design using MD simulations
- ELISA, column chromatography, gel electrophoresis, scFv libraries and flow cytometry, surface plasmon resonance
- Biosensor design and imaging: high throughput screening based on 96/384 well plates and fluorescence-activated cell sorting (FACS), methods based on liquid handling robots, confocal and epifluorescence imaging, live cell imaging, perfusion assay for cultured cells/neurons
- Molecular dynamic (MD) simulations using GROMACS to study protein structure-function analysis, biomolecule and peptide design, synthetic gene design based on novel bioinformatics/MD simulations approaches
- Computer-aided design: DNA/protein sequence analysis, protein-peptide interaction studies using MD simulations, antigen-antibody interactions, protein-ligand docking, protein-peptide docking, protein structure prediction and evaluation, pharmacophore mapping, statistical analysis
- PhD in Biochemical Engineering