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About Arc Institute

Arc Institute is an independent nonprofit research organization at the interface of artificial intelligence and biology, working to accelerate scientific progress and understand the root causes of complex diseases. Founded in 2021 and based in Palo Alto, Arc partners with Stanford University, UC Berkeley, and UC San Francisco.

Unlike academia, our scientists have long-term funding and industry-like resources. Unlike industry, they're free to pursue high-risk, long-term research without commercial pressures. Arc's Technology Centers and Core Investigator labs work side by side, integrating experimental and computational biology under one roof to tackle problems neither could solve alone.

Our two Institute Initiatives reflect this model in action:

• Virtual Cell Initiative: Building a full-stack virtual cell model to identify disease mechanisms and nominate drug targets,  accelerating the path from biological insight to clinical trials.
• Alzheimer's Disease Initiative: Mapping the genes, pathways, and environmental factors behind Alzheimer's disease to develop drug candidates that address root causes.

More than 300 Arconauts work together at our Palo Alto headquarters, backed by substantial long-term philanthropic funding.

About the position

We are seeking a highly skilled and motivated Scientist with a strong background in cellular engineering and stem cell biology to join the Molecular Engineering team within the Genome Engineering Technology Center at the Arc Institute. In this role, you will design, generate, and characterize engineered human pluripotent stem cell (hPSC) lines for arrayed genetic perturbation screens in complex organoid models used to recapitulate and probe human genetics of neurodegenerative disorders. Examples of engineering projects include developing optimized effector systems for gene knockdown and activation that function robustly throughout differentiation, introducing rare coding variants to model disease-associated mutations, and implementing novel genome engineering technologies to expand perturbation capabilities. Through this work, you will play a critical role in the Institute's Alzheimer's Disease Initiative, an ambitious cross-functional effort aimed at identifying and drugging rational therapeutic targets to combat devastating neurodegenerative disorders.

This position is highly collaborative and the candidate will have an unique opportunity to interface with pioneering labs that have developed the fundamental toolbox for genome engineering and functional genomics screens, such as CRISPR nucleases, CRISPRi, CRISPRoff, CRISPRa, and serine or bridge recombinases.

About you

• You are passionate about science and excited about answering questions related to molecular design, genome engineering technology development, and complex human diseases.
• You embrace challenges and often formulate creative solutions to develop new approaches and optimize existing tools to answer complex biological questions.
• You understand the importance of collaboration and thrive when working with a diverse team of scientists.
• You have a deep commitment to data quality while working in a fast-paced environment.
• Your organizational skills enable you to manage multiple concurrent projects, and your curiosity and creativity drive you to continuous learning and innovation.

In this position you will

• Develop and optimize engineered hPSC lines for arrayed genetic perturbation screens in complex organoid models, applying genome engineering strategies tailored to the desired edit and experimental goals.
• Design and implement systematic approaches to identify, benchmark, and optimize effector systems for gene knockdown and activation that function robustly throughout differentiation to disease-relevant cell types.
• Execute clonal isolation, expansion, and comprehensive characterization of engineered cell lines, applying and refining established quality control standards and assays to ensure functionality, stability, and reproducibility across multiple engineering approaches.
• Support the cross-functional execution of arrayed genetic perturbation screens for the Alzheimer's Disease Initiative at Arc. 
• Serve as a key technical resource for cellular engineering of stem cells, partnering with researchers across Arc's Tech Centers and Core Labs to support a wide range of experimental applications and flexibly implement genome engineering approaches based on key biological questions and downstream requirements.
• Present findings at internal meetings and external conferences, and contribute to scientific publications.
• Stay updated on the latest developments in the fields of genome engineering, stem cell biology, and cellular engineering, actively seeking out opportunities for innovation and technology adoption.

Requirements

• PhD in Molecular Biology, Bioengineering, Genetics, or a related field.
• 0-3 years of post-PhD research experience (industry or academia).
• Experience with genome and cell line engineering in stem cells, leveraging a range of genome engineering strategies (CRISPR-Cas9 knock-in, recombinase systems, base editing, prime editing, etc.) and performing comprehensive characterization including on-target validation, off-target assessment, and functional validation of edited cell lines.
• Experience with and enthusiasm for applying cutting-edge molecular tools to disease modeling and function-based screening, and implementing application-driven iterative, systematic technology maturation.
• A collaborative mindset and enthusiasm for mentoring and working within a cross-functional team.
• Strong project management skills with the ability to plan, execute, and deliver results on time.

Preferred Qualifications

• Experience differentiating hPSCs into neural or immune lineages; microglia differentiation experience highly desirable.
• Experience with transcriptional modulation systems (CRISPRi/a) for functional genomics screens, including effector optimization and performance benchmarking.
• Proficiency with computational tools for analyzing genomics data (Python, R, or similar).
• Experience with LIMS systems, ideally Benchling.

The base salary range for this position is $121,250 - $159,500. These amounts reflect the range of base salary that the Institute reasonably would expect to pay a new hire or internal candidate for this position. The actual base compensation paid to any individual for this position may vary depending on factors such as experience, market conditions, education/training, skill level, and whether the compensation is internally equitable, and does not include bonuses, commissions, differential pay, other forms of compensation, or benefits. This position is also eligible to receive an annual discretionary bonus, with the amount dependent on individual and institute performance factors.