# The Center for High Content Functional Annotation of Natural Products

> **NIH NIH U41** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $976,696

## Abstract

It has been well documented that the outcomes of success for botanical clinical trials have been poor, leading
to greater effort into understanding the basic mechanisms underlying their activity. While it is often
hypothesized that botanicals or other complex mixtures work through synergistic or additive processes, there
are few proven examples. There is also growing belief to support the role of gut microbiome metabolism for
generation of active metabolites, however, relatively few experimental results back this up. This is driven by
limitations in obtaining clear biological signatures in relevant biological assays, in accurately defining the
chemical constitution of complex mixtures, and in the informatics approaches to bring these disparate data
types together. This proposal aims to address these important questions by the development and
implementation of technology platforms. In project 1, we will employ highly innovative orthogonal cell-based
high content phenotypic screening approaches in primary macrophages, epithelial cells, primary neurons,
which will give us comprehensive coverage of signaling pathway and receptor that are believed to be relevant
to botanicals. These platforms aim to link botanicals/bioactive molecules of interest together with information
about their molecular targets. These platforms have been demonstrated to work with complex mixtures as well
as pure compounds and are supported by the development of bioinformatic approaches that allow integration
of orthogonal biological activity. Our second project will take advantage of developments in untargeted
metabolomics, along with feature reduction, to have a robust pipeline to clearly define the constitution of
complex mixtures. Our third project specifically addresses the question of synergy and additivity by the
development of informatics approaches that use the comprehensive biological and chemical signatures
generated in the other projects. In this project, we will develop universal tools that will allow the community to
probe their own biological and chemical assay results to generate compound/activity maps. This program will
deliver critical technology platforms for the in-depth study of botanicals and natural products and deliver tools
that can be used by the community

## Key facts

- **NIH application ID:** 10200677
- **Project number:** 5U41AT008718-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Nadja B Cech
- **Activity code:** U41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $976,696
- **Award type:** 5
- **Project period:** 2015-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200677

## Citation

> US National Institutes of Health, RePORTER application 10200677, The Center for High Content Functional Annotation of Natural Products (5U41AT008718-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10200677. Licensed CC0.

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