# TR&D 6: Targeted Top Down

> **NIH NIH P41** · NORTHWESTERN UNIVERSITY · 2020 · $248,130

## Abstract

Technology Research & Development Project 6: Targeted Top Down Proteomics
Abstract
The National Resource for Translational and Developmental Proteomics (NRTDP) has invested significant
resources into a discovery pipeline that efficiently generates interesting candidate proteoforms for further
investigation. While these experiments produce valuable insight into cell and disease biology, they are labor
intensive and relatively low throughput, thus rendering application of this pipeline to larger sample cohorts
significantly challenging. Therefore, we propose the development of a complementary targeted quantitative
workflow enabling further interrogation of interesting proteoforms in a high throughput modality with enhanced
sensitivity. Automated immunoprecipitation will provide the foundation of this new platform. Here, we will draw
on the experience of our collaborators at Thermo Pierce, who have validated thousands of antibodies and
implemented automated immunocapture using the KingFisher Flex system. Once immunoprecipitated, samples
will be resolved via liquid chromatography, ultimately transitioning to the CESI 8000 capillary electrophoresis
system from Sciex for improved sensitivity. For each target, we will develop a proteoform reaction monitoring
(PfRM) assay that validates and quantitates all of the proteoforms present at stoichiometric levels. The resulting
data will be processed using a new software platform, PFRM VIEWER, with the finalized PfRM assays made freely
available to the scientific community through a portal on the Resource website. These combined innovations will
enable the Resource to advance further down the pathway to translational proteomics by confirming observations
in larger populations while also providing a roadmap for community members to implement these assays within
their own respective research initiatives.

## Key facts

- **NIH application ID:** 9854766
- **Project number:** 2P41GM108569-06
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** NEIL L KELLEHER
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,130
- **Award type:** 2
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854766

## Citation

> US National Institutes of Health, RePORTER application 9854766, TR&D 6: Targeted Top Down (2P41GM108569-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9854766. Licensed CC0.

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