Postdoctoral Associate, Rare Disease Mechanisms and Drug Discovery

Broad Institute • Cambridge, MA

7d • Onsite

About The Position

The Neal Laboratory within the Broad Institute’s Novo Nordisk Foundation Center for Genomic Mechanisms of Disease seeks an independent, creative postdoctoral researcher to investigate how genetic variants cause rare diseases and translate those findings into potential treatments. This position is part of Project Encore, an NIH Director’s Transformative Research Award-funded initiative addressing how to systematically identify potential treatments across many genetic disorders. The approach combines barcoded open reading frame (ORF) expression libraries, multiplexed fluorescence imaging, and in situ barcode sequencing to assess compound effects 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-associated cellular phenotypes.

This experimental research position emphasizes technology development, rigorous screening, and biological discovery. The postdoctoral associate will develop and apply pooled optical screening approaches and investigate promising compound–variant interactions in collaboration with computational biologists and disease-area collaborators. The researcher will help develop the platform and use its findings to build an independent mechanistic research program, selecting research questions and approaches.

The 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. The position is on-site at the Broad Institute in Cambridge, Massachusetts, with a flexible start date as early as possible. Applications will be reviewed on a rolling basis until the position is filled.

Requirements

• 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 skills, strong organizational skills, and a collaborative approach to research.

Nice To Haves

• Experience in mechanistic cell biology, human genetics, or research on Mendelian or rare diseases.
• Experience with genetic perturbation screens, barcoded library construction, lentiviral transduction, or cell line engineering.
• Experience with automated or high-content microscopy, compound screening, multiplexed immunostaining, or in situ sequencing and related optical profiling methods.
• Experience with disease-relevant cell models, including human iPSCs, differentiated lineages, or primary cells.
• Experience with quantitative image analysis or scientific programming, including CellProfiler, Fiji, Python, or R.

Responsibilities

• Design and optimize pooled optical screens connecting disease-associated variants with protein localization and high-dimensional cellular phenotypes.
• Refine multiplexed staining, imaging, and in situ sequencing workflows.
• Develop promising variant phenotypes or compound responses into mechanistic research projects using approaches suited to the research question.
• Test hypotheses in disease-relevant cell models, including iPSC-derived or primary human cells where appropriate, in collaboration with disease-area experts.
• Conduct primary compound screens and secondary dose-response experiments, with attention to assay performance, controls, and reproducibility.
• Collaborate with computational colleagues to interpret imaging data, prioritize findings, and design informative follow-up experiments.
• Lead manuscript preparation and present findings.
• Contribute openly accessible datasets and methods.
• Mentor junior researchers.

Benefits

• Medical insurance
• Dental insurance
• Vision insurance
• Life insurance
• Disability insurance
• 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
• Employee assistance program
• Mentorship and research training
• Support in applying for external fellowships

What This Job Offers

• Job Type: Full-time
• Career Level: Senior
• Education Level: Ph.D. or professional degree