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

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.

Responsibilities:

-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: nucleic acid extraction, PCR/qPCR, molecular cloning

-Experience with CRISPR/Cas9 and genome editing approaches

-Experience with next-generation sequencing library preparation (RNA-seq, single-cell RNA-seq)

-Familiarity with base editing or other precision genome editing tools (highly desirable)

-Hands-on experience working with Drosophila

-Knowledge of fly genetics, husbandry, and embryo manipulation

-Experience with transgenic organism generation or genetic crosses

-Familiarity with developmental biology assays and embryo staging

-Experience with fluorescence microscopy and confocal imaging

-Knowledge of high-throughput screening approaches or automated imaging systems

-Image analysis skills using software such as ImageJ/FIJI, or similar platforms

-Proficiency in at least one programming language (Python, R, or similar)

-Familiarity with bioinformatics tools and genomic databases

-Statistical analysis skills for large datasets

-Knowledge of transcriptional regulation and enhancer biology

-Understanding of massively parallel reporter assays (MPRAs)

-Knowledge of machine learning or computational modeling is preferred

-Project management skills for handling multiple experimental workflows

-Ability to design, manage, and conduct experiments independently, as well as in a collaborative context

-Experience in writing and contributing to scientific reports, manuscripts for publication, and intramural/extramural grant proposals

-Commitment to mentoring undergraduate and graduate students

-Good Laboratory Practices, and respect for lab safety

-Demonstrated leadership in other aspects of academic life, such as teaching or service

-Excellent written and verbal communication

-Meticulous record-keeping and strong organizational skills

-Strong publication record in peer reviewed journal

• 3 required (contact information only)

UC Berkeley is committed to diversity, equity, inclusion, and belonging in our public mission of research, teaching, and service, consistent with UC Regents Policy 4400 and University of California Academic Personnel policy (APM 210 1-d). These values are embedded in our Principles of Community, which reflect our passion for critical inquiry, debate, discovery and innovation, and our deep commitment to contributing to a better world. Every member of the UC Berkeley community has a role in sustaining a safe, caring and humane environment in which these values can thrive.

The University of California, Berkeley is an Equal Opportunity employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, or protected veteran status.

For more information, please refer to the University of California's Affirmative Action and Nondiscrimination in Employment Policy and the University of California's Anti-Discrimination Policy.

In searches when letters of reference are required all letters will be treated as confidential per University of California policy and California state law. Please refer potential referees, including when letters are provided via a third party (i.e., dossier service or career center), to the UC Berkeley statement of confidentiality prior to submitting their letter.

As a University employee, you will be required to comply with all applicable University policies and/or collective bargaining agreements, as may be amended from time to time. Federal, state, or local government directives may impose additional requirements.

Unless stated otherwise, unambiguously, in the position description, this position does not include sponsorship of a new consular H-1B visa petition that would require payment of the $100,000 supplemental fee.

As a condition of employment, the finalist will be required to disclose if they are subject to any final administrative or judicial decisions within the last seven years determining that they committed any misconduct.

• "Misconduct" means any violation of the policies or laws governing conduct at the applicant's previous place of employment, including, but not limited to, violations of policies or laws prohibiting sexual harassment, sexual assault, or other forms of harassment or discrimination, as defined by the employer.
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