Zyphore - Principal Scientist, Protein Sciences & Engineering

About Zyphore
Zyphore is a cutting-edge biotechnology company focused on developing enzyme-based therapeutics to address diseases of metabolism and inflammation. By leveraging proprietary enzyme engineering, half-life extension (HLE), and immunogenicity shielding technologies, Zyphore aims to revolutionize enzyme-based therapeutics and provide best-in-class (BIC) therapies for patients.
Position Overview
The Principal Scientist, Protein Sciences + Engineering will lead the development and optimization of Zyphore’s Protein Engineering and Half-Life Extension (HLE) strategies to enhance enzyme stability, activity, and immune shielding. This role will be an employee of Zyphore, a Raven / RA Capital portfolio company. This role will lead efforts in protein engineering, applying molecular biology, structural biology, and computational tools to design and optimize therapeutic proteins with enhanced function, stability, and developability, with a proven ability to lead cross-functional scientific teams. You will drive scientific innovation while collaborating closely with colleagues in discovery biology, immunology, and translational science.

This is a high-impact, hands-on leadership role ideal for a protein scientist passionate about creating biologics that make a difference for patients.

Key Responsibilities

• Design, engineer, and optimize therapeutic proteins (e.g., enzymes, fusion proteins, cytokines, antibodies) for function, stability, manufacturability, and reduced immunogenicity.
• Apply rational design, directed evolution, display technologies (phage, yeast, or mammalian), and/or AI-guided approaches to protein optimization.
• Guide the selection and development of expression systems and purification strategies.
• Protein expression, purification and characterization to support preclinical studies.
• Characterize biophysical and biochemical properties of engineered proteins, including binding affinity, aggregation, thermal stability, and solubility.
• Develop and perform plate-based enzymatic kinetics, activity, and protein stability assays.
• Execute molecular cloning and construct variant libraries.
• Collaborate cross-functionally to align protein design with biological function, assay development, and downstream translational goals.
• Manage external partnerships with CROs, consultants, or academic labs as needed.
• Maintain detailed electronic lab notebooks and communicate findings effectively to the scientific team.
• Collaborate with cross-functional team members and external partners to drive programs aligned with strategic goals.
• Contribute to intellectual property strategy and write technical sections for patents and regulatory documents.
• Mentor junior scientists and help build a culture of scientific excellence and collaboration.

Qualifications

• PhD in Protein Engineering, Structural Biology, Biochemistry, Molecular Biology, or related field.
• 7+ years of industry experience in therapeutic protein design and optimization.
• Deep expertise in protein expression, purification, characterization, and engineering strategies.
• Proficiency with protein modeling tools, structural data interpretation, or computational design platforms.
• Well versed in protein engineering techniques including rational and semi-rational mutagenesis, computational design.
• Strong experience in protein library screening; proficiency in plate-based high-throughput assay development and automation is highly preferred.
• Proficient in molecular biology techniques, including PCR, mutagenesis, cloning, transformation, transfection.
• Strong data analysis and communication skills, with the ability to present findings to both technical and non-technical audiences.
• Proven ability to collaborate effectively with internal cross-functional teams and external partners.
• Enthusiastic about learning new technologies and scientific advancements.
• Adaptable to a fast-paced environment and capable of managing diverse tasks.
• Excellent communication and presentation skills, with the ability to convey technical information clearly and concisely.
• Track record of innovation and scientific contributions (e.g., publications, patents, IND support).

Preferred Qualifications

• Experience working in early-stage biotech or platform technology development.
• Familiarity with CMC considerations and developability assessments.
• Familiarity with directed evolution and experience with yeast and phage display methods is a plus.
• Experience with bioconjugation and biopolymer strategy & execution.
• Understanding of immunogenicity and mitigation strategies.
• Experience in high-throughput assay development and process automation.

What We Will Offer You