Postdoctoral Associate - Neal Laboratory

Position overview

The Neal Laboratory within the Broad Institute's Novo Nordisk Foundation Center for Genomic Mechanisms of Disease seeks an independent, creative Postdoctoral Associate to discover how genetic variants drive rare disease and translate those insights into potential treatments. The position is part of Project Encore, a new initiative funded by an NIH Director's Transformative Research Award( neallab.org/encore ).

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 builds on the observation that disease-associated variants can disrupt protein localization and cellular organization. By combining barcoded open reading frame (ORF) expression libraries, multiplexed fluorescence imaging, and in situ barcode sequencing, we can evaluate the effects of each compound across hundreds of variants in parallel. 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-associatedcellular phenotypes.

This is an experimental research position emphasizing technology development, rigorous screening, and biological discovery. You will develop and apply pooled optical screening approaches and investigate promising compound–variant interactions in close collaboration with computational biologists and disease-area collaborators. We are looking for a scientist who wants to help develop the platform and use its findings to build an independent mechanistic research program, choosing which questions to
pursue and how to answer them.

Key Responsibilities

- Develop screening technologies. Design and optimize pooled optical screens that connect disease-associated variants with protein localization and high-dimensional cellular phenotypes.
- Refine multiplexed staining, imaging, and in situ sequencing workflows.
- Pursue the biology. Choose promising variant phenotypes or compound responses and develop them into mechanistic projects, using whatever approaches the question demands.
- Test hypotheses in disease-relevant cell models, including iPSC-derived or primary human cells where appropriate, in collaboration with disease-area experts.
- Lead compound screening and validation.
- Conduct primary screens and secondary dose -response experiments, with careful attention to assay performance, controls, and reproducibility.
- Integrate experiments and analysis. Work with computational colleagues to interpret imaging data, prioritize findings, and design informative follow-up experiments.
- Communicate and share discoveries. Lead manuscript preparation and present findings, contribute openly accessible datasets and methods, and mentor junior researchers.

Required qualifications
- A Ph.D. in molecular biology, cell biology, genetics, functional genomics, bioengineering, chemical
- biology, systems biology, or a related field.
- Strong hands-on experience in mammalian cell culture, molecular biology, and fluorescence microscopy.
- Demonstrated ability to design, troubleshoot, and interpret experiments and advance a research
- project independently, as shown by first-author publications or preprints.
- Clear written and verbal communication, strong organizational skills, and a collaborative approach to research.

Preferred Experience

Expertise in all areas is not expected, but candidates with experience in more than one of these areas will be prioritized:

- Mechanistic cell biology, human genetics, or research on Mendelian or rare diseases.
- Genetic perturbation screens, barcoded library construction, lentiviral transduction, or cell line engineering.
- Automated or high-content microscopy, compound screening, multiplexed immunostaining, or in situ sequencing and related optical profiling methods.
- Disease-relevant cell models, including human iPSCs, differentiated lineages, or primary cells.
- Quantitative image analysis or scientific programming, including tools such as CellProfiler, Fiji, Python, or R.

Mentorship and career development

- The Neal Laboratory emphasizes scientific independence, collaborative research, and career
- development. Postdoctoral researchers receive mentorship and research training to support future
- leadership roles in academia or industry and are encouraged and supported in applying for external
- fellowships.

Position details
- Start date: Flexible; as early as possible
- Location: On-site, Broad Institute, Cambridge, MA

How to apply

- Please submit a CV, contact information for three references, and a brief cover letter.
- In your cover letter, describe your research interests and relevant experience, and briefly sketch one or two questions you would be excited to pursue in our lab.
- Applications will be reviewed on a rolling basis until the position is filled.
- We are also recruiting for a complementary position in Computational and Experimental Functional
- Genomics in Rare Disease for researchers interested in personally combining experimental biology with computational analysis and method development

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.