Assistant Project Scientist - Functional Genomics and Developmental Biology

Assistant Project Scientist - Functional Genomics and Developmental Biology

Assistant Project Scientist – Functional Genomics and Developmental Biology – Molecular and Cell Biology

Position overview:

The Garcia Lab in the Molecular and Cell Biology department at UC Berkeley is recruiting for an Assistant Project Scientist. Over the last few decades, impressive progress has been made in uncovering how embryonic development is driven by genes connected in complex regulatory networks. The research goal of the Garcia Lab is to endow these networks with quantitative and molecular information that makes it possible to precisely predict how the gene expression patterns that dictate cellular identity are prescribed by input activators and repressors, and the arrangement of binding sites for these transcription factors on the DNA.

Models are tested by systematically varying DNA regulatory architecture and by inventing new technology to perform precision measurements of the flow of information along the central dogma.

The incumbent will support ongoing projects aimed at understanding how the number, placement, and affinity of transcription factor binding sites dictates gene regulatory programs in multicellular organisms. This involves locating the binding sites within a regulatory region, then systematically modulating the binding site arrangements, while simultaneously measuring the effect of modulation on output gene expression. Massively parallel reporter assays (MPRAs) have made this possible in high‑throughput in single‑cell cultures.

To enable MPRAs in multicellular organisms, we have generated tools to create a high degree of mutagenesis in specific genomic loci in vivo using base editing. The lab has developed a novel base editing approach using a sea lamprey‑derived enzyme (AID evoCDA1) combined with CRISPR technology that creates targeted mutations in specific DNA regions within living Drosophila. This system can mutate 200–500 base pair stretches and successfully alter gene expression patterns in a developmental enhancer.

This position focuses on scaling‑up this mutagenesis technology to create an MPRA‑like system for whole organisms. The work involves three main objectives:
1) optimizing the base editing system for better coverage,
2) implementing automated imaging to analyze thousands of enhancer variants, and
3) developing sequence‑based methods to measure how mutations affect gene activity. Essentially, bringing the power of high‑throughput enhancer analysis from cell culture into living animals.

• Optimize base editor mutagenesis systems to improve coverage and efficiency across targeted enhancer regions
• Test and implement alternative Cas9 variants and gRNA targeting strategies to enhance mutagenic capacity
• Design and validate gRNA arrays for targeting multiple enhancers simultaneously
• Develop and establish high‑throughput imaging pipelines for phenotyping mutant Drosophila embryos
• Generate large libraries of enhancer variants using the AIDevoCDA1 base editing system
• Prepare samples for bulk and single‑cell RNA sequencing experiments
• Perform next‑generation sequencing library preparation and quality control
• Conduct molecular cloning and transgenic fly line generation as needed
• Analyze imaging data to quantify gene expression changes across mutant variants
• Process and analyze RNA‑seq data to correlate enhancer mutations with transcriptional output
• Integrate mutagenesis data with expression readouts to map functional binding sites
• Maintain detailed experimental records and databases of enhancer variants
• Present findings at lab meetings and contribute to manuscript preparation
• Collaborate with team members on experimental design and troubleshooting
• Mentor and train junior laboratory personnel in research design, techniques, and protocols

• PhD or equivalent international degree

• At least 4 years of post‑doctoral research experience

• PhD in Molecular & Cell Biology, Developmental Biology, Genetics, Biophysics, or related field.
• Demonstrated expertise in molecular genetics, including…