Job Description
Note:
This position is laboratory-based, onsite role.
Job Summary:
- Based in Rahway, NJ the Mass Spectrometry & Biophysics (MSB) team is an integral part of the Computational & Structural Chemistry Department within Discovery Chemistry.
- Working across all therapeutic areas & supporting teams at all network sites we focus our efforts in 3 principal areas to drive end-to-end pipeline impact.
- Screening & Hit-to-Lead. Discovery & optimization of ligands across the modality spectrum (fragments, small molecules, bifunctional degraders, pepProducts, therapeutic proteins) to identify leads that modulate our targets of interest.
Elucidating Mode of Interaction. - Detailed characterization of how our ligands interact with and modulate our targets of interest at the molecular level.
Understanding Mechanism of Action. - Determining how perturbing our targets of interest affects disease pathology both in vitro and in vivo.
- To achieve all of the highlighted activities, our team combines state-of-the-art capabilities and expertise in 4 key areas.
- We collaborate closely with project teams to craft a holistic approach appropriate for each program & question at hand:
Protein Biochemistry. - We provide carefully designed, high-quality and thoroughly characterized proteins for screening and assay development. Leveraging our expertise across target classes (including integral membrane proteins & multi-subunit complexes) and utilizing both internal & external resources.
- We partner directly with teams to produce proteins that are qualified for even the most challenging applications.
- Biophysics & Biochemistry. Using a toolbox of techniques including SPR, fluorescence/CD spectroscopy, calorimetry, nano-DSF & radioligand binding we perform detailed thermodynamic & kinetic profiling of protein-ligand interactions across all modalities.
- BioNMR. Our capabilities in high-resolution NMR spectroscopy enable us to rigorously study the solution behavior of proteins (including excipient and self-association effects) and to conduct detailed experiments probing molecular interactions using both ligand- and protein-detected techniques.
- Mass Spectrometry. We specialize in biophysical mass spectrometry including HDX-MS for protein characterization, binding site mapping and epitope/paratope determination; metabolic flux as a readout for pharmacodynamics and pathway engagement in physiologically relevant settings (both in vitro and in vivo); and ultrahigh-throughput mass spectrometry where we have partnered with groups across the network to enable screening, chemical reaction profiling and protein engineering.
- Our overarching goal is to work directly with teams to accelerate the discovery and characterization of molecules on the path to delivering meaningful therapies to patients.
Core responsibilities:
- Run routine radioligand binding assay protocols, analyze data & generate weekly reports, carry out tissue culture and cell-based binding assays.
- Fully document all experiments in our electronic laboratory notebook.
Education:
- B.Sc. with 6+ years or M.Sc. with 4+ year or
- PHD with 3+ years of laboratory experience practicing the required skills.
Must Haves/Required skills:
- Prior experience developing equilibrium and kinetic radioligand binding assays (e.g. 125I, 3H, 35S) in relevant formats is preferred, or willingness to do radioligand work.
- Tissue culture including: (i) cell plating, (ii) cell stimulation and (iii) cell harvesting.
- Experience in membrane preparation
- Experience working with multiwell plates (96- and 384-well formats)
Nice to haves/Preferred skills:
- Experience with liquid handling automation systems (e.g. Echo, Bravo).
- Familiarity with multi-mode plate readers such as the SpectraMax and EnVision Multilabel Reader.
- Exporting and dose-response fitting of data from binding assays.
- Running research operating plan assay and data upload (ROP assay, Activity Base application)
- Experience with traditional Western blot techniques, including requisite data analysis used to determine abundance of given protein targets.
- Knowledge of the Protein Simple high-throughput, automated western blotting system is preferred but not required.
Computer/Software skills:
- MS Office suite, Adobe PDF –must have
- Prior experience with an electronic laboratory notebook system is desirable but not required.
- Prior experience with data analysis packages including GraphPad Prism, Activity Base, etc. is desirable but not required.
Personality: Team oriented, detail oriented, highly collaborative, Preductule, and understands timelines.