Scientist/Sr Scientist, Protein Engineering

Earli is seeking a highly motivated and scientifically rigorous Scientist/Senior Scientist to join our Therapeutics Group. This is a hands-on, bench-based role in which you will drive the design, engineering, and functional characterization of novel protein-based therapeutic candidates targeting the tumor microenvironment and the immune system's response to cancer.

You will bring deep expertise in molecular/protein design and medium-throughput mammalian protein expression/purification systems, combined with a strong immunology or immuno-oncology foundation to design, express, and functionally characterize immune agonist payloads using primary immune cells. You will work at the intersection of protein science and translational immunology, partnering closely with the broader Therapeutics and Platform teams to advance Earli's pipeline from early-stage discovery through preclinical proof-of-concept.

This position reports to the Head of Therapeutics.

• Design novel protein therapeutics—including cytokines, immune agonists, fusion proteins, bispecific constructs (multi-domain and 2A-based), leveraging structure-function knowledge and/or computational tools to guide engineering hypotheses.
• Engineer protein variants to optimize potency, selectivity, half-life, manufacturability, or other developability attributes relevant to DNA encoded oncology applications.
• Identify strategies to improve candidate properties based on experimental outcomes.
• Stay current with the scientific literature on protein therapeutics, bispecific engager biology, cytokine engineering, and relevant tumor immunology to inform design decisions.

• Develop and execute medium-throughput transient mammalian expression workflows (HEK293, CHO, or equivalent) to produce protein candidates for functional evaluation.
• Optimize expression constructs (signal sequences, tags, codon usage, linkers) to maximize yield, potency and solubility of challenging therapeutic formats.
• Perform His or Fc based affinity purification; characterize proteins by SDS-PAGE, SEC, ELISA, and other relevant analytical methods.
• Characterize efficiency of mRNA transcription and protein translation and address bottlenecks.
• Establish quality criteria to prioritize candidates for to functional assays; maintain comprehensive records of expression and purification outcomes.

• Design, develop, and execute functional assays in relevant cancer cell lines and primary human immune cells (PBMCs, T cells, NK cells, monocytes/macrophages) to evaluate candidate activity, potency, and selectivity.
• Utilize flow cytometry, cytokine profiling (Luminex, CBA, ELISA), proliferation, cytotoxicity, and signaling assays to characterize potential candidates.
• Design and execute tumor microenvironment (TME)-relevant in vitro model systems, including co-culture platforms, to assess immunological mechanism of action (MoA).
• Contribute to development of high-content or medium-throughput screening platforms for candidate triage in collaboration with the broader team.

• • Contribute original scientific thinking to project strategy, experimental design, and data interpretation; present findings to internal teams and leadership clearly and compellingly.
  • Collaborate cross-functionally with Platform Biology, Delivery, and Computational teams to integrate protein therapeutics within Earli's cancer-activated gene expression system.
  • Proactively identify scientific risks and propose mitigation strategies; drive projects forward with appropriate urgency in a fast-paced startup environment.
  • Author and maintain clear experimental records, SOPs, and internal research reports; contribute to external publications and patent disclosures as appropriate.
  • Mentor junior scientists and research associates where appropriate; model a culture of intellectual rigor, curiosity, and collaboration.

• Ph.D. in Immunology, Biochemistry, Molecular Biology, Protein Engineering, Cancer Biology, or a closely related field with 4+ years of postdoctoral or industry experience; OR M.S./B.S. with 8+ years of directly relevant industry experience.
• Solid molecular biology skills: multi-component gene cloning, mammalian vector design, PCR/qPCR, and standard biochemical assays (Western blot, ELISA).
• Hands-on expertise in recombinant protein expression in mammalian systems (HEK293, CHO) including transient transfection, construct design, and small-scale purification.
• Strong background in cellular and molecular immunology, with deep understanding of the innate and adaptive immune response in the context of cancer.
• Experience designing and executing in vitro functional assays in cancer cell lines and primary human immune cells; proficiency in multiparameter flow cytometry.
• Track record of generating high-quality, reproducible data and clear scientific communication in presentations and written reports.
• Ability to integrate and collaborate into a high achieving team environment.
• Ability to handle multiple projects simultaneously and meet aggressive project timelines.
• Exceptional verbal communication and scientific writing.
• Desire to continue to continue in a laboratory focused role.

• Industry experience in biotherapeutics discovery, particularly in oncology.
• Experience with cytokine engineering, immunocytokines, bispecific antibodies or T cell engagers, or other immunomodulatory therapeutic formats.
• Familiarity with tumor microenvironment biology and ex vivo TME modeling approaches.
• Experience with high-throughput or automated expression/assay platforms.
• Structural biology intuition (PyMOL, AlphaFold) or familiarity with computational protein design tools to inform engineering decisions.
• Experience with viral and non-viral gene delivery methods (lentivirus, AAV, mRNA, LNP) for cell line engineering or functional studies.
• Track record of scientific publication and/or patent contributions.

The anticipated base salary for this position is $110,000-$145,000 per year.