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

Broad Institute•Cambridge, MA

11d•Onsite

About The Position

The Neal Laboratory at the Broad Institute is hiring a Research Associate II for Project Encore, a rare disease drug discovery project funded by an NIH Director's Transformative Research Award. Encore combines cells carrying barcoded disease-associated variants, multiplexed fluorescence imaging, and in situ barcode sequencing to investigate 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 role focused on careful, reproducible experimental work and teamwork. The Research Associate will execute day-to-day screening workflows, from cell preparation and compound treatment through staining, sequencing, and imaging. The role also includes improving assays and performing molecular biology and follow-up experiments in collaboration with postdoctoral researchers and experimental and computational colleagues. Training will be provided in project-specific screening, staining, imaging, in situ sequencing, and biosafety procedures for lentiviral work (BSL-2+). The research associate will participate in scientific discussions and develop skills in experimental design, troubleshooting, data interpretation, and scientific communication. With experience, the associate may take greater ownership of workflows and contribute to assay development, follow-up studies, and resulting publications. The laboratory also supports research associates interested in graduate or medical school, including mentorship on applications.

Requirements

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; experience may come from undergraduate research, internships, or employment in an academic or industry laboratory.
Careful experimental technique, strong attention to detail, and 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 willingness to learn and troubleshoot new methods.
Ability to work independently after training and seek guidance when needed.

Nice To Haves

Experience with mammalian cell culture.
Experience with fluorescence microscopy, immunostaining, or automated imaging.
Experience with compound screening, plate-based assays, or liquid-handling equipment.
Experience with lentiviral transduction, cell line engineering, molecular cloning, or barcoded genetic libraries.
Experience with 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.

Responsibilities

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.
Perform compound treatments, multiplexed immunostaining, in situ barcode sequencing, and automated fluorescence imaging.
Coordinate multistep workflows across screening plates, follow established protocols, and work with the team to refine them.
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.
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.
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.
Prepare reagents, maintain organized cell and sample inventories, track supplies, and assist with shared laboratory work.
Contribute to a safe, organized, and collaborative laboratory environment.