Senior Scientist, In Vivo Functional Genomics - Neuroscience

About Arc Institute

The Arc Institute is a new scientific institution conducting curiosity-driven basic science and technology development to understand and treat complex human diseases. Headquartered in Palo Alto, California, Arc is an independent research organization founded on the belief that many important research programs will be enabled by new institutional models. Arc operates in partnership with Stanford University, UCSF, and UC Berkeley.

While the prevailing university research model has yielded many tremendous successes, we believe in the importance of institutional experimentation as a way to make progress. These include:

• Funding: Arc will fully fund Core Investigators' (PIs') research groups, liberating scientists from the typical constraints of project-based external grants.
• Technology: Biomedical research has become increasingly dependent on complex tooling. Arc Technology Centers develop, optimize and deploy rapidly advancing experimental and computational technologies in collaboration with Core Investigators.
• Support: Arc aims to provide first-class support-operationally, financially and scientifically-that will enable scientists to pursue long-term high risk, high reward research that can meaningfully advance progress in disease cures, including neurodegeneration, cancer, and immune dysfunction.
• Culture: We believe that culture matters enormously in science and that excellence is difficult to sustain. We aim to create a culture that is focused on scientific curiosity, a deep commitment to truth, broad ambition, and selfless collaboration.

Arc scaled to nearly 100 people in its first year. With $650M+ in committed funding and a state of the art new lab facility in Palo Alto, Arc will continue to grow quickly to several hundred in the coming years.

About the position

We are seeking a highly skilled and motivated Snr Scientist with a strong background in neurobiology to join the In Vivo Functional Genomics team inside the Mammalian Models Technology Center at Arc Institute.

In this position you will play a critical role in developing two of Arc's overarching goals: the Virtual Cell (VCI) and the Alzheimer Disease Initiatives (ADI). The VCI will integrate in vivo functional genomics approaches with predictive modeling to establish causal gene-phenotype connections and, ultimately make accurate predictions of cellular states and their response to interventions to advance our understanding of human biology.The ADI, will use functional genomics to interrogate specific genetic circuits of relevance in neurodegeneration in mammalian models of Alzheimer's Disease (these targets are currently being nominated using large-scale screens performed by Arc's Cellular Models Tech Center). The successful candidate will use and develop functional genomics methods to generate in vivo perturbation datasets with single-cell resolution at unprecedented scale across all brain cell types. This work will represent a milestone in understanding the genetic circuits that shape brain cellular identities and how they are misregulated in neurodegenerative processes.

In this context, you will have the opportunity to partner closely with pioneering labs that have developed the fundamental toolbox for 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 cell function and cell-cell communication, immunology, neurobiology and complex human diseases.
• You enjoy working with animal models and value the benefit this type of research brings to scientific discovery.
• You are excited to develop new approaches and combine different tools to answer complex questions in vivo.
• You are creative and are excited to try new ways of tackling problems beyond the technique/approaches you are familiar with. You enjoy stepping out of your comfort zone to learn new things and develop new experimental approaches.
• You work fast but detail-oriented. You are good at troubleshooting. You are careful and diligent about good documentation practices and keeping things organized while moving at a rapid pace.
• You love to collaborate and help others. Science is a team effort, and you pride yourself in taking the initiative to help.

In this position you will

• Lead our in vivo screen projects in the brain with a high degree of independence and continued support from the rest of the team. Our goal is to perform genome-wide in vivo screens (loss and gain of function) across the main brain lineages (neurons, astrocytes, oligodendrocytes and microglia) using expression (Perturb-seq) and morphology (in situ sequencing) as readout of perturbation states. Your work will involve experimental planning, in vivo delivery of CRISPR libraries, readout (single-cell + spatial) and data analysis. These two last points will be performed in collaboration with the Multiome and Computational Tech Centers at Arc.
• Test and benchmark different genetic perturbation modalities in vivo: CRISPR-KO, CRISPRi, CRISPRa, ORF overexpression.
• Explore & develop new delivery methods (viral vectors, nanoparticles, microvesicles, etc) to enable delivery of large payloads in a tissue selective manner.
• Train and mentor Research Associates and establish standardized protocols for use in Arc's labs.
• Embrace the opportunity to creatively collaborate with Core Investigators on ad hoc early research projects and with other Technology Centers to push our Virtual Cell Atlas and Alzheimer's Disease Initiatives.
• Keep up-to-date on advances in the field by reading the literature and attending key Conferences.
• Analyze data and present at meetings and seminars.
• The successful candidate will be an ambitious self-starter, be motivated to apply his/her skills to diverse projects and enjoy working in a collaborative and fast-paced team environment

Requirements

• PhD in biology, genetics, or another relevant field with 4+ years of experience in neurobiology.
• Experience working with in vivo models.
• Extensive experience in at least two of the following areas:

• • Large scale single-cell RNAseq profiling of brain cell types.
  • High-throughput CRISPR screens.
  • Brain delivery methods: viral vectors, synthetic nanoparticles, microvesicles, etc.

• Strong project management skills with the ability to plan, execute, and deliver results on time.
• Extensive troubleshooting experience.
• Demonstrated ability to work both independently and in a highly collaborative multidisciplinary environment.

Preferred Qualifications

Expertise in any of the following areas will be considered an additional asset for this role:

• Ability to analyze large and complex data sets using Python, R, or similar tools.
• Experience in stereotactic surgeries.
• Single-cell ATACseq and other epigenomic workflows
• Microscopy & Histology
• Experience with mammalian models (other than mice)

The base salary range for this position is $131,750 to $162,750. 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.