Consultant: Senior Protein/Peptide Mass Spectrometry Scientist

Arinale Biosciences Incorporated

Arinale Biosciences is a biotechnology startup operating in stealth mode after recently being spun out of one of New York City’s premier academic medical centers. Occupying a unique position at the nexus of scientific discovery and healthcare, Arinale’s platform for rapid development of paradigm-changing therapeutics will extend the benefits of precision medicine far beyond current limitations and fundamentally improve human. We are helping create a future where every diagnosis is clearer, every decision is more confident, and every patient has more hope.

Mission

Guided by vision and powered by innovation, we will catalyze the discovery and development of a new generation of transformative precision therapies.

Role

We are seeking a senior protein/peptide mass spectrometry scientist to lead experimental design, instrument operation, and data analysis focused on chemoproteomics. Extensive experience in chemical proteomics — activity-based protein profiling, covalent probe chemistry, and chemoproteomic enrichment workflows — is central to this role and considered a critical, must-have qualification, not a supplementary one. A successful candidate will integrate with wet-lab and computational teams, collaborating on sample preparation strategy, method development, and end-to-end interpretation of complex proteomic and chemoproteomic datasets. Ideal candidates will have hands-on mastery of the mass spectrometer itself, from tuning and troubleshooting through to spectral interpretation, and will enjoy the creative challenge of translating fragmentation and covalent-labeling data into confident, well-quantified protein and peptide identifications.

Timeline

We are seeking a consultant for an initial 6-month engagement. The position entails several specific deliverables, including development and optimization of protocols for specific chemoproteomic approaches, as well as data acquisition and analyses of a few, select proteomics studies. Potential for continuation as a full-time employee at Arinale Biosciences upon successful completion of consulting contract.

Location

This position is in New York (NY) and requires full-time, in-person work in a laboratory setting.

Responsibilities

• Lead chemical proteomics workflows, including activity-based protein profiling (ABPP) and covalent probe/warhead-based target and off-target identification

• Design and execute chemoproteomic labeling, bioorthogonal click chemistry conjugation, and affinity enrichment workflows to map reactive and ligandable sites across the proteome

• Setup, operate and tune LC-MS/MS platforms (e.g., Orbitrap, Q-TOF, triple quadrupole, ion trap) to ensure optimal sensitivity, resolution, and mass accuracy

• Design bottom-up, top-down, and targeted (MRM/SRM/PRM) proteomics experiments tailored to the biological question

• Select and optimize protease digestion, reduction/alkylation, and chemical or isobaric labeling strategies (e.g., TMT, iTRAQ, SILAC)

• Develop and optimize PTM enrichment workflows (e.g., IMAC/TiO2 phosphopeptide enrichment, immunoprecipitation, glycopeptide enrichment)

• Select and optimize fragmentation methods (CID, HCD, ETD, EThcD) for peptide sequencing and PTM localization Perform database searching, statistical validation (target-decoy FDR, PEP), and quantitative analysis of MS data

• Troubleshoot instrument performance issues, chromatographic coupling problems, and unexpected spectral artifacts

• Generate reports and visualizations summarizing identification, quantification, and PTM localization results

• Collaborate with biologists and computational scientists on experimental design and data interpretation

• Communicate results (oral, written) to colleagues, collaborators, and stakeholders

• Mentor junior scientists and maintain SOPs for sample preparation and instrument operation

• Maintain knowledge of state-of-the-art instrumentation, workflows, and best practices

Requirements Education (one of the following is required):

• PhD in Analytical Chemistry, Biochemistry, Chemical Biology, Proteomics, or a related field, or

• Master’s degree in one of the above fields and 5+ years of relevant industry experience

Chemical proteomics (hands-on experience in several of the listed skills is critical):

• Activity-based protein profiling (ABPP) using reactivity-based covalent probes (e.g., cysteine-, serine-, or lysine-reactive electrophiles)

• Covalent probe/warhead chemistry: experience designing, selecting, and evaluating chemical probes and warheads (e.g., chloroacetamides, acrylamides, epoxides, photoaffinity groups), including assessment of probe selectivity, reactivity, and off-target labeling

• Bioorthogonal and linker chemistry: proficiency with click chemistry conjugation (CuAAC/SPAAC) and cleavable linker strategies (e.g., azo, DADPS, TEV) for chemoproteomic enrichment and selective elution of labeled peptides

• Quantitative and competitive ABPP: proficiency in workflows such as isoTOP-ABPP and TMT-ABPP for covalent inhibitor characterization, off-target profiling, and druggability/hotspot mapping

• Chemoproteomic sample workflows: hands-on skill with probe treatment, click conjugation, streptavidin/biotin affinity enrichment, on-bead digestion, and LC-MS/MS analysis of covalently modified peptides

• Covalent site localization and quantification: ability to localize, validate, and quantify covalent modification sites and residue-level target occupancy directly from MS data

Skills in MS sample preparation and instrument operation (a high level of self-sufficiency is required):

• Hands-on experience operating and troubleshooting ESI/MALDI mass spectrometers (e.g., Orbitrap, Q-TOF, triple quadrupole, or FT-ICR)

• Proficiency with fragmentation methods (CID, HCD, ETD, EThcD) and their application to peptide sequencing and PTM localization

• Skilled in enzymatic digestion (trypsin, Lys-C, Glu-C, chymotrypsin), reduction/alkylation chemistry, and isobaric/metabolic labeling strategies

• Experience with PTM enrichment techniques (e.g., phosphopeptide/glycopeptide enrichment, immunoprecipitation, crosslinking)

Experimental design, analysis and interpretation (advanced proficiency expected):

• Experience designing bottom-up, top-down, or targeted proteomics experiments, including appropriate controls and replication

• Proficiency with database search engines (e.g., Mascot, Sequest, MaxQuant) and quantitative proteomics software (e.g., Skyline, Perseus)

• Understanding of FDR estimation, protein inference, and PTM site localization scoring (e.g., Ascore)

• Strong interdisciplinary communication skills

Standout Experiences:

• Additional postdoctoral or industry experience in proteomics/chemoproteomics

• Experience with top-down or native mass spectrometry approaches

• Crosslinking mass spectrometry for structural and protein interaction studies

• Design of novel covalent probes for previously intractable or undrugged protein classes

• Contributions to covalent fragment-based or DNA-encoded library (DEL) screening campaigns

• Fluency in scripting languages (e.g., Python, R) for custom data analysis pipelines

• Experience with cloud or HPC environments for large-scale proteomics data processing

• Publication record in peer-reviewed proteomics or chemical biology journals

Compensation

• $120,000-$140,000

• Negotiable payment structure: entirely milestone-based compensation strategy or a hybrid of milestones and hourly compensation.