About This Role
The Chemical Biology & Proteomics group is seeking a highly motivated Research Fellow to advance the application of chemoproteomics to drug discovery. This 18-month position offers an opportunity to work at the interface of chemical biology, proteomics, and pharmacology, leveraging covalent chemical probes and state-of-the-art mass spectrometry to understand target engagement, selectivity, and mechanism of action in biologically relevant systems.
The successful candidate will develop and apply chemoproteomic methods to profile covalent inhibitors in live cells, characterize proteome-wide selectivity, and identify ligandable proteins that may represent new therapeutic opportunities. Working closely with medicinal chemists, biologists, and proteomics scientists, the Fellow will contribute to innovative drug discovery programs while gaining exposure to industrial research and development.
What You'll Do
- Design and execute chemoproteomic experiments to characterize target engagement and proteome-wide selectivity of covalent small molecules in cells and tissues.
- Perform live-cell labeling experiments followed by bioorthogonal click chemistry, enrichment workflows, and mass spectrometry-based proteomic analysis.
- Establish and optimize workflows for profiling reactive and ligandable amino acid residues, including cysteine-directed chemoproteomic approaches.
- Conduct mammalian cell culture experiments and prepare samples for LC-MS/MS analysis using quantitative proteomics methods.
- Analyze large-scale proteomic datasets to identify on-target and off-target protein interactions and generate actionable insights for drug discovery teams.
- Collaborate closely with medicinal chemistry, biology, pharmacology, and computational scientists to guide compound optimization and candidate selection.
- Evaluate emerging chemoproteomic technologies and implement new methodologies to expand platform capabilities.
- Present research findings at internal project meetings and scientific conferences and contribute to peer-reviewed publications.
Required Skills
- Ph.D. in Chemical Biology, Chemistry, Biochemistry, Pharmaceutical Sciences, Proteomics, or a related discipline.
- Strong background in chemical biology, covalent ligand discovery, or activity-based protein profiling.
- Hands-on experience with bioorthogonal chemistry, including click chemistry-based probe labeling and enrichment workflows.
- Experience performing mammalian cell culture and biochemical experiments involving small molecules and chemical probes.
- Experience preparing samples for LC-MS/MS-based proteomics and familiarity with modern quantitative proteomic workflows.
- Knowledge of protein biochemistry, target engagement assays, and mechanism-of-action studies.
- Demonstrated ability to independently design experiments, analyze data, and communicate scientific findings.
- Strong publication record and evidence of scientific creativity and innovation.
- Excellent written and verbal communication skills and ability to work effectively in multidisciplinary teams.
Preferred Qualifications
- Experience with chemoproteomic methods such as ABPP, isoTOP-ABPP, cysteinome profiling, or residue-centric proteomics.
- Familiarity with quantitative proteomics approaches including TMT, DIA, PRM, or targeted mass spectrometry.
- Experience analyzing proteomics datasets using software such as FragPipe, MaxQuant, DIA-NN, or related tools.
- Knowledge of covalent inhibitor design, electrophile reactivity, and target occupancy measurements.
- Experience with affinity enrichment strategies, streptavidin-based pulldowns, and probe development.
- Knowledge of protein biochemistry, target engagement assays, and mechanism-of-action studies.
- Interest in applying chemical biology technologies to neurodegeneration and other challenging disease areas.
