# Development of an OPTogenetic InteractoMics Assay (OPTIMA)

> **NIH NIH R21** · DANA-FARBER CANCER INST · 2020 · $417,853

## Abstract

Project Summary/Abstract
Over the last decade, it has become increasingly clear that a more complete understanding of human diseases
requires viewing them in the context of systems biology, in particular through a comprehensive understanding of
a network of molecular interactions that occur in a cell. Numerous successful applications (e.g. for disease gene
prioritization) build on the fact that the local and global structures of molecular networks, mostly based on protein-
protein interactions (PPIs), provide critical biological information. With the release of several large-scale
systematic PPI datasets since our group produced the first proteome-scale map of the human binary interactome
in 2005, integration of genetic and clinical data with interactome information has become possible and provides
meaningful and critical insights towards a deeper pathophysiological understanding of diseases and the potential
to revolutionize precision medicine. However, we have not reached a comprehensive map of the PPI network in
any model system or in humans yet, and thus clinical applications would greatly benefit from deeper and wider
explorations of the human interactome.
High-throughput approaches have been developed to determine PPIs on a global scale for many organisms, but
these assays remain intrinsically limited and labor intensive. A major bottleneck in screening is determining the
identities of binary interacting partners. This OPTIMA project aims to eliminate that bottleneck and fill the gap in
current networks by developing a novel disruptive technology for high-performance interactomics allowing en
masse screening of PPIs to provide comprehensive binary PPI maps. This innovative system will result from the
integration of two recently validated technologies, on the one hand the bioluminescent detection of PPIs based
on complementation of a split-Nanoluc reporter and, on the other hand, one of the most sensitive optogenetically
programmed promoters driving DNA barcode fusion. By leveraging en masse binary PPI detection, this new
binary interaction detection strategy will dramatically enhance the overall coverage of proteome-scale
interactome maps. This new high-throughput pipeline will be orthogonal to existing proteome-scale binary
interaction mapping platforms, such as yeast two-hybrid followed by validation, and thus able to significantly
enhance the available tools to expand existing interactomes.

## Key facts

- **NIH application ID:** 10057519
- **Project number:** 1R21HG010934-01A1
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Michael A Calderwood
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,853
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057519

## Citation

> US National Institutes of Health, RePORTER application 10057519, Development of an OPTogenetic InteractoMics Assay (OPTIMA) (1R21HG010934-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057519. Licensed CC0.

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