Research Associate II - Optical Pooled Screening and Rare Disease Drug Discovery

Position Title: Research Associate II

Laboratory: Neal Laboratory

Center: Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute

Project: Project Encore (funded by an NIH Director's Transformative Research Award | neallab.org/encore )

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Project Description

Encore addresses a central challenge in rare disease research: how can we systematically search for potential treatments across many genetic disorders at once? Our approach combines cells carrying barcoded disease-associated variants, multiplexed fluorescence imaging, and in situ barcode sequencing to measure how compounds affect protein localization and cellular organization. The project aims to screen thousands of compounds, including approved drugs, across more than 1.6 million compound–variant combinations to identify candidates that reverse disease-associated cellular phenotypes.

This is a hands-on laboratory position emphasizing careful experimental work, reproducibility, and teamwork. You will take responsibility for the day-to-day execution of screening workflows, from cell preparation and compound treatment through staining, sequencing, and imaging. You will also help improve assays and carry out molecular biology and follow-up experiments, working closely with postdoctoral researchers and other members of the experimental and computational team. We are looking for someone who enjoys learning new techniques, solving practical experimental problems, and generating reliable data that enable scientific discovery.

Key Responsibilities

- Maintain and prepare cell models: Culture, expand, and maintain mammalian cell lines used in screening experiments. Prepare cells for assays, monitor cell health, perform lentiviral transduction, and help generate cells carrying barcoded variant libraries.
- Carry out optical pooled screens: Perform compound treatments, multiplexed immunostaining, in situ barcode sequencing, and automated fluorescence imaging. Coordinate multistep workflows across screening plates, following established protocols and working with the team to refine them.
- Ensure data quality and reproducibility: Evaluate cell preparation, staining, and image quality; identify and communicate experimental problems; and work with computational colleagues to assess screening performance. Maintain accurate records of plate layouts, sample identities, reagent batches, experimental conditions, and protocol changes.
- Perform molecular biology and follow-up experiments: Carry out molecular cloning, DNA preparation, and sequencing-based library quality control. Perform secondary dose-response assays and other cell-based experiments to evaluate promising compound–variant interactions.
- Troubleshoot and communicate results: Help identify sources of experimental variability, test protocol improvements, and document optimized methods. Summarize results and observations for team discussions, and contribute experimental data and methods to scientific publications.
- Support shared laboratory work: Prepare reagents, maintain organized cell and sample inventories, track supplies, and assist where needed. Contribute to a safe, organized, and collaborative laboratory environment.

Qualifications & Experience

Required Qualifications

- A bachelor's degree in biology, molecular or cell biology, biochemistry, biotechnology, bioengineering, or a related field.
- Hands-on laboratory research experience, including mammalian cell culture and basic molecular biology. Relevant experience may come from undergraduate research, internships, or employment in an academic or industry laboratory.
- Careful experimental technique, strong attention to detail, and the ability to follow multistep protocols, maintain accurate records, and organize work across multiple experiments.
- Clear written and verbal communication, a collaborative approach to research, and a willingness to learn and troubleshoot new methods. Ability to work independently after training and seek guidance when needed.

Preferred Experience

Experience in any of the following areas would be valuable; prior experience with optical pooled screening is not required:

- Mammalian cell culture.
- Fluorescence microscopy, immunostaining, or automated imaging.
- Compound screening, plate-based assays, or liquid-handling equipment.
- Lentiviral transduction, cell line engineering, molecular cloning, or barcoded genetic libraries.
- In situ sequencing, multiplexed labeling, or other imaging-based molecular assays.
- Basic quantitative image analysis or data analysis using tools such as Fiji, CellProfiler, Python, or R (programming experience is not required).

Training and Career Development

The Neal Laboratory emphasizes collaborative research, mentorship, and career development. Training will be provided in project-specific screening, staining, imaging, and in situ sequencing workflows, as well as in biosafety procedures for lentiviral work (BSL-2+). The research associate will work closely with experienced researchers, participate in scientific discussions, and develop skills in experimental design, troubleshooting, data interpretation, and scientific communication. As proficiency grows, there will be opportunities to take greater ownership of experimental workflows and contribute to assay development and follow-up studies, with opportunities for authorship on resulting publications.

Many research associates go on to graduate or medical school, and we actively support those goals, including mentorship on applications.

Position Details

- Start Date: Flexible; as early as possible
- Expected Commitment: Two years preferred
- Location: On-site, Broad Institute, Cambridge, MA
- Salary: Depending on experience

How to apply

Please submit a résumé or CV, contact information for two or three references (including at least one research mentor), and a brief cover letter. In your cover letter, tell us why this position interests you, describe your relevant laboratory experience and your specific contributions to previous research projects, and share what you hope to learn or do next. Applications will be reviewed on a rolling basis until the position is filled.

The expected base pay range for this position as listed above is based on a 40 hour per week schedule. Broad provides pay ranges representing its reasonable and good faith estimate of what the organization reasonably expects to pay for a position at the time of posting. Actual compensation will vary based on factors including but not limited to, relevant skills, experience, education, qualifications, and other factors permissible by law. At Broad, your base pay is just one part of a comprehensive total rewards package. From day one, this role offers a competitive benefits package (https://www.broadinstitute.org/benefits/benefits-working-broad) including medical, dental, vision, life, and disability insurance; a 401(k) retirement plan; flexible spending and health savings accounts; at least 13 paid holidays; winter closure; paid time off; parental and family care leave; and an employee assistance program, among other Broad benefits.
The Broad Institute is an equal opportunity employer. All qualified applicants will receive consideration for employment without regard to race, national origin, religion, age, color, sex, disability, protected veteran status, or any other characteristic protected by local, state, or federal laws, rules, or regulations.
Should you need a reasonable accommodation to complete the application or interview process, please contact [email protected] for assistance.