Senior Scientist, In Vivo Functional Genomics

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 Senior Scientist with a strong background in in vivo experimentation using mammalian models 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: Virtual Cell and Alzheimer Disease initiatives. In the Virtual Cell initiative, you will participate in creating the first foundation model that makes accurate predictions of cellular states and their response to interventions, we expect to generate this by applying deep learning to large in vivo perturbation datasets. In the Alzheimer Disease Initiative, we will set up new mammalian research models for neurodegeneration and use in vivo perturbation screens to identify rational therapeutic targets for this devastating neurodegenerative disorder. 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.

The successful candidate will lead projects aimed at generating large-scale in vivo perturbation datasets across diverse cell types, tissues and organs. We will initially focus on the brain and immune systems to foster discovery of therapeutic approaches for neurodegenerative and immune diseases. In parallel, you will test novel genome engineering methods and develop delivery strategies to enable new in vivo functional genomics approaches and pave the way for discovery of both fundamental biological principles and applied solutions to disease.

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 brain and immune systems with a high degree of independence and continued support from the rest of the team. This involves experimental planning, delivery of CRISPR libraries using different strategies (injections, surgery, etc) and analysis of perturbation outcomes using expression (Perturb-seq) and/or morphological (in situ sequencing, etc) readouts.
• Establish new mammalian models to interrogate neurodegenerative diseases. You will set up breeding colonies of these model systems and establish transgenesis and perturbation methods on them.
• 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 the use of 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 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 or 5+ years of postdoctoral experience in academia and/or industry.
• 4+ years of experience using mammalian models and in vivo approaches, including generation of transgenic animals and phenotypic analysis.
• Extensive experience in animal handling, colony management and surgery. Techniques of special interest: tail-vein and retro-orbital injections, intra-femoral injection, stereotactic surgery.
• Experience using in vivo delivery methods: viral vectors, synthetic nanoparticles, microvesicles, etc.
• Experience in using Flow cytometry to isolate primary cells from different tissues. Special interest in immune and brain cells: HSCs, T-cells, monocytes, neurons, glia.
• Strong project management skills with the ability to plan, execute, and deliver results on time. Extensive troubleshooting experience is a very important asset for this role.
• 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:

• Experience in mammalian models (other than mice)
• CRISPR-Cas9 or other genome editing tools, 
• Viral vector production: Lenti, AAV, HSV, etc 
• Single-cell RNAseq and other genomic workflows
• Spatial transcriptomics. 
• Microscopy & Histology
• Ability to analyze large and complex data sets using Python, R, or similar tools.

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.