Scientist, Nucleic Acid Biochemistry, Hsu & Konermann Labs

Arc Institute•Palo Alto, CA

20h•Onsite

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. 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.

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.
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.

Nice To Haves

Experience 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.

Responsibilities

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.