What are the responsibilities and job description for the Postdoctoral Associate, Rare Disease Mechanisms and Drug Discovery position at Broad Institute?
General information
Description & Requirements
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-associated cellular 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
Salary : $70,000 - $92,667