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

The Hsu Lab and Konermann Lab are seeking applications for a Scientist in Nucleic Acid Biochemistry at the Arc Institute in Palo Alto, CA, focusing on mechanistic dissection and engineering of Bridge Recombinases—naturally occurring RNA-guided DNA recombinases that we recently discovered and showed can programmably insert, excise, and invert DNA (Nature, 2024; Science, 2025). The candidate will drive the next phase of Bridge Recombinase evolution. Building on our work establishing IS110 and ISCro4 as programmable tools, you will be part of an interdisciplinary team with the goal to engineer bridge RNAs and recombinases for megabase-scale genome modifications, therapeutic gene circuit integration, and scarless disease correction. 

In this role, you will lead the mechanistic program that underpins this effort. You will design and execute rigorous in vitro assays to mechanistically interrogate how bridge recombinases, in complex with their bridge RNAs, recognize target and donor DNA and catalyze strand exchange across all three recombination modalities—insertion, inversion, and excision. Your work will define the parameters that govern recombinase activity, specificity, and the balance between productive and off-pathway outcomes.

About you

• You are driven by science. The world of science is filled with so many unanswered questions and the opportunity to address these questions brings you purpose.
• You are a mechanist. You are energized by the prospect of turning a black-box activity into a quantitative model, and you believe that well-designed biochemistry is one of the most powerful ways to guide engineering.
• You are a collaborator. You love working with people of different backgrounds and brainstorming how hard questions can be broken down and addressed.
• You are intellectually independent and self-motivated to push the boundaries of novel technologies.
• You are an optimizer. In research, there’s always a race against the clock. You care deeply about making every step of the way as close to perfect as possible but also as quick and efficient as possible.
• You build tools. As much as you love answering specific scientific questions, you also love creating assays and platforms that are scalable and useful across many application areas.

In this position you will

• Lead the mechanistic research program on bridge recombinases, including planning, execution, and analysis of experiments across insertion, inversion, and excision modalities.
• Purify recombinant bridge recombinases and reconstitute functional ribonucleoprotein complexes with bridge RNAs and target/donor DNA substrates.
• Develop and apply quantitative in vitro assays—including kinetic, binding, footprinting, and single-turnover/multi-turnover recombination assays—to dissect substrate recognition, complex assembly, strand exchange, and product release.
• Develop higher-throughput biochemical platforms (e.g., plate-based, fluorescence-coupled, or sequencing-based readouts) to enable variant triage and support directed evolution and rational engineering campaigns in the lab.
• Partner with structural biologists to design biochemically informed constructs and substrates, interpret cryo-EM and crystallographic data, and close the loop between structure and function.
• Advance cell biology efforts by helping to reconcile in vitro activity and specificity with behavior in mammalian cells, including by designing assays that recapitulate cellular activity or constraints
• Collaborate closely with the PI on planning and executing scientific research projects, and help shape the broader biochemical strategy of the bridge recombinase program.
• Mentor Research Associates and work with graduate students and other scientists in the lab.
• Develop and provide training to lab personnel as needed, and develop standardized protocols for the lab.
• Keep up-to-date on advances in the field by reading the literature and attending key conferences.
• Publish preprints and journal articles; present findings at conferences.

Requirements

• PhD in biochemistry, molecular biology, biophysics, or a related life sciences or engineering field, with 0-4 years of postdoctoral or equivalent industry experience.
• Demonstrated expertise in mechanistic biochemistry of nucleic acid–protein complexes, including protein purification and reconstitution of functional RNP or protein–DNA complexes.
• Hands-on experience designing and executing quantitative biochemical assays.
• Experience working with gene editing enzymes that act on DNA—CRISPR-Cas9, recombinases, transposases, nucleases, or integrases—is strongly preferred.
• Experience developing higher-throughput biochemical assays (e.g., plate-based fluorescence readouts, NGS-coupled activity or specificity profiling, barcoded substrate libraries) is a strong plus.
• Mammalian and/or insect cell culture experience preferred. 
• Conceptual fluency in structural biology (cryo-EM and/or X-ray crystallography) sufficient to collaborate effectively with structural biologists, design constructs and substrates for structural studies, and interpret structural data in a functional context. Hands-on structural experience is welcome but not required.
• Familiarity with cell-based assays for genome editing activity is a plus.
• Strong written and verbal communication skills.
• Experience and enthusiasm for mentoring research trainees, including graduate students and RAs.
• The successful candidate will be an ambitious self-starter, an innovative and meticulous researcher, and enjoy working in a collaborative and fast-paced team environment.