Technologies drive scientific progress

The role that advanced technologies play in scientific breakthroughs is hard to ignore: CRISPR, induced pluripotent stem cells, and single cell sequencing transformed entire fields of research. By the same token, the barriers to achieving quantum leaps in biological understanding are often technical in nature.

Across the scientific enterprise, first-rate technology development, careful benchmarking, and systematic optimization are often decoupled from deep biological or disease expertise. As a result, platform technologies are often advanced in an engineering-focused environment that, in some cases, is quite far removed from the burning scientific questions that should define technology goals. Such a disconnect presents a major barrier to advancing new biomedical technologies beyond the proof of concept stage.

Achieving an optimal balance of these capabilities requires interdisciplinary teams, generous funding with explicit recognition for rigorous technological optimization, and a shift in typical academic incentive structures. In industry, increased capital and larger teams can come with the tradeoff of a narrower purview for talented industry scientists, who are researching under time constraints often dictated by corporate or non-scientific priorities. Handoffs between academic and industry sectors are a common workaround for these issues, but they are not always ideal for knowledge and know-how transfer.

At Arc, we aim to merge the best aspects of academia and industry, enabling long-term teams to develop purpose-driven technologies in tight iteration with impactful biomedical problems. Our mission is to accelerate scientific progress by getting the incentive structures right.

Arc's Technology Centers

To achieve our goals, Arc is building five Technology Centers: biotech-like technology R&D hubs that will partner with our Core Investigators to develop and apply advanced technologies to unlock new discoveries across human complex diseases by tackling five technological areas: Multi-Omics, Genome Engineering, Cellular Models, Mammalian Models, and Computation. Arc Technology Centers will form one of the three pillars of the Arc model, parallel to the high-risk research in our Investigators’ labs and our investment in infrastructure supporting the translation of biomedical discoveries into clinical breakthroughs.

State-of-the-art technology development requires cross-functional teams united around a common goal. Take a field like single cell sequencing, for instance, where experts in sequencing technology, microfluidics, software development, statistics, informatics, genomics, instrumentation, and chemistry all needed to come together to make a transformative leap forward in biology. These partnerships rarely happen in academia, and in other fields, they have been exceedingly difficult to fund and integrate. This kind of interdisciplinary teamwork is a key tenet of Arc’s Technology Centers.

Beyond inventing new technologies, the Centers will systematically onboard, benchmark, and refine scientific technologies - something that is often unfundable in academic labs, but which we believe is a critical part of driving technological innovation. Understanding what works and what doesn’t, and why, is the first step toward closing the innovation gap and creating new technologies that serve an important unmet need.

Finally, we’ve all seen how much of a difference open dissemination and documentation of new technologies can make in the scientific community. The explosion of CRISPR gene editing is a great example, fueled by rapid plasmid and protocol sharing and community-driven open-source tools with wide utility in mind. Arc will follow this lead by encouraging our Technology Centers to disseminate protocols, datasets, open-source software, and resources broadly to enable reproducibility and ensure that our technologies are transformative not only for Arc Investigators but across the scientific community.

A team-based approach

Arc Technology Centers have the broad mandate of developing and implementing new groundbreaking technologies in close collaboration with Arc Investigators pursuing curiosity-driven biomedical science. We expect many Technology Center scientists will have experience in the biotech industry, bringing expertise in teamwork, scalability, and rigorous optimization. Once at Arc, they’ll have the opportunity for expanded technological scope and autonomy, driving innovation across a wide range of areas from neurodegeneration to cancer and immunology.

Importantly, each Technology Center team won’t work in a vacuum - rather, they will collaborate closely with the other Technology Centers, enabling cross-functional workflows and interdisciplinary working groups, as well as with Arc Investigators working across different areas of human biology. Our Technology Center teams will provide intellectual and creative leadership for research directions at the Institute and serve as key subject matter experts in their technological domains. This merging of industry and academic cultures and competencies is the secret sauce of Arc, and we’re excited by the potential of bringing together great people from both sectors.

Each Center will be led by a Senior Director: an experienced people manager who will build a team of 10-20 scientists at various levels (Principal Scientists, Senior Scientists, Group Leaders, Research Associates). Senior Directors will allocate a research budget toward technology-focused research efforts that is fully funded by Arc. Additionally, some Technology Centers will incorporate embedded core facilities, such as a sequencing facility within the Multi-Omics Center. Compartmentalizing the core facility as a substructure within the Center clearly delineates core services within the broader scope of each Technology Center as a driving force at the cutting edge of technology development.

What kind of science will the Technology Centers tackle?

High-throughput discovery science in human biomedicine relies on ways to profile, interrogate, and manipulate genomes, epigenomes, transcriptomes, and proteomes. That is why two of our inaugural Centers will be focused on Multi-Omics and Genome Engineering.

The Genome Engineering Center will focus on both functional genomics and genome engineering effector development. With an explosion of technology development in this area across academia and industry over the past few years, it is more important than ever to evaluate and benchmark existing tools in a systematic way, and then build purpose-driven technologies in this space to reach the full potential of genome engineering. Thinking beyond CRISPR, the Genome Engineering Center will strive to discover, develop, and refine new capabilities for genome, epigenome, and transcriptome manipulation. They will also push the boundaries of resolution, throughput, and sensitivity to develop powerful functional genomics platforms to enable unbiased discovery science across cell types of interest championed by the Cellular Models Center.
Our Multi-Omics Center will develop, optimize, and apply cutting edge technologies for DNA, RNA, and protein analyses, including single cell and spatial approaches, to enable high-throughput and multi-dimensional cellular characterization. When done right, unbiased and integrative omic techniques not only lead to the generation of new testable hypotheses, but can also provide systems-level insights to uncover emergent properties.

Existing cellular and mammalian models are still very limited in their ability to effectively model complex phenotypes like neurodegeneration or cancer-immune cell interactions. This is especially evident when you consider that only a small percentage of drugs that are effective in animal studies actually succeed in human trials. To help bridge this gap, we are building a Cellular Models Center and a Mammalian Models Center to create new and better models for complex disease, in close collaboration with the Genome Engineering Center and Arc Investigators.

The Cellular Models Center will encompass 2D and 3D in vitro cellular models, spearheading Arc’s technology development for organoid culturing, genetically engineered cellular models, patient-derived iPSCs, and other ex vivo systems to model the complexity of uniquely human diseases in a scalable, reproducible, and engineerable way. Initially, the Center will focus on cellular and organoid models that better recapitulate human biology in neurodegenerative diseases, exploring interactions between cell types and organs.
The Mammalian Disease Models Center will partner with Arc Investigators to engineer animal models of complex diseases, advancing beyond common rodent species to more accurately recapitulate human physiology, pathology, and treatment response. This Center will create important resources for the entire scientific community to better interrogate complex diseases where there are currently no good models. It will also play a critical role in Arc’s drive toward therapeutically relevant biomedical discoveries and their translation.

Working closely with all these Centers is the Computation Center, where software developers and bioinformaticians will devise exciting new ways to extract insights out of big data, helping to generate new hypotheses and build predictive models of cellular function. The Computation Center will also play a major role in discovery science at Arc, for example by working with the Genome Engineering and Multi-Omics Centers on new effector discovery and with the Models Centers to better understand and model human genetic variation.

The Computation Center will spearhead the development of biological software and algorithms to analyze biomedical data in increasingly powerful ways. Arc Institute Investigators, as well as the other Technology Centers, will collaborate with the Computation Center’s software engineers and computational biologists to integrate many types of multi-dimensional datasets toward predictive models of cellular function. Critically, the close proximity of wet lab and computational scientists will enable a tight feedback loop between computational analysis and experimental design and execution for model refinement. They will also play a crucial role in building and maintaining systems for high-utility data and software dissemination. Long relegated to the back burner in academic biomedical science, we believe that an investment into biological software development will address a major gap in modern research.

Joining Arc

If this sounds like something you want to be a part of, we’re in the process of hiring Senior Directors for each of the Tech Centers, followed by Scientist positions at all experience levels within each Center. These are permanent, fully funded positions based in the Arc laboratory in Palo Alto, CA, offering industry-competitive salaries, ample opportunities for career growth and leadership, and the unique combination of curiosity-driven high-risk academic research with biotech-like technological rigor. Check out our current available positions - we hope you’ll apply to join us!