Consultant: Senior Protein/Peptide Mass Spectrometry Scientist

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, musthave

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