Scientist, Molecular Engineering

Arc InstitutePalo Alto, CA
6h

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.

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.

Nice To Haves

  • 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.

Responsibilities

  • 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.
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