Senior Scientist, Assay Development; Chemistry

Position: Staff / Senior Scientist, Assay Development (Chemistry)
About Glyphic:

At Glyphic Biotechnologies, we plan to create the protein revolution for which scientists and researchers have been waiting. We are developing a massively parallel, single-molecule proteome sequencing platform that will transform life science discovery and usher in a new era of insights into human biology and disease. To date, we have raised >$80M from venture partners and non-dilutive grant funding to achieve our vision of next generation proteome sequencing.

What we are looking for in you

We are seeking a Senior or Staff Scientist to join our Assay Development team at a critical stage in platform development. Reporting to the Director of Assay Development, you will be a hands-on expert working at the chemistry-assay interface - developing the chemical methods that enable reliable, high-efficiency sample loading into our expansion assay, and building the novel conjugation, cleavage, and stabilization workflows that power our single-molecule proteome sequencing platform.

You will work closely with the Chemistry team to develop sample input methods for new protein and peptide types, including side-chain protection strategies, encoder loading routes, and peptide-from-protein handoff approaches.

The ideal candidate brings deep expertise in peptide chemistry, bioorthogonal and click conjugation strategies, and cleavage chemistry development - with a track record of building new chemical methods for complex, multi-component systems. You combine a synthetic chemist's mechanistic rigor with sensitivity to how chemistry performs inside a demanding multi-cycle assay environment.

This is a full-time, exempt, in-person position with work conducted at our Berkeley, CA location.

What you'll do

Expansion assay chemistry & sample loading

• Optimize bioconjugation methods for peptide loading into the expansion assay; establish robust, high-efficiency loading protocols that perform reliably across diverse peptide populations and physicochemical characteristics.
• Identify, characterize, and optimize peptide labeling during the ProSE sequencing assay, leveraging mechanistic understanding of Edman chemistry and amino acid side-chain reactivity and stability.
• Develop reagents and methods to maximize the stability of peptides, DNA, and peptide-DNA chimeras throughout the ProSE sequencing assay.
• Partner with the Chemistry team to develop amino acid side-chain protection chemistries.
• Evaluate compatibility of new chemistries with existing assay components, reagents, and multi-cycle sequencing conditions.
• Evaluate emerging chemistries from the literature and internal pipeline; synthesize and test candidate reagents.

Novel assay chemistry workflows

• Design and determine the order of operations for chemical manipulations within the assay workflow - including decisions on when specific steps occur on-bead versus off-bead, and how side-chain protection and deprotection strategies are sequenced relative to assay cycles - to ensure compatibility, efficiency, and analytical interpretability.
• Optimize selective cleavage chemistry workflows for use within the sequencing assay.
• Optimize for efficiency, selectivity, and compatibility with assay conditions.
• Develop stabilization strategies for sensitive assay intermediates and conjugates.
• Employ analytical methods - HPLC (RP and IEX), LC-MS/MS, UV-Vis, CE - to characterize conjugation efficiency, adduct identity, purity, and stability of assay intermediates and conjugates.
• Characterize and troubleshoot the impact of the chemical steps of multi-cycle workflows.

What you need

Required:

• Advanced degree in organic chemistry, chemical biology, biochemistry, or a related field
• Industry experience designing multi-step chemical workflows in complex biological systems, including sequencing or determining the order of chemical manipulations across assay conditions.
• MS/PhD with 6+/4+ years of experience (for Senior Scientist)
• MS/PhD with 8+/6+ years of experience (for Staff Scientist)
• Demonstrated experience developing site-selective bioconjugation chemistry for native peptides - including N-terminal, C-terminal, and side-chain modification strategies - using click chemistry (CuAAC, SPAAC, IEDDA),…