Integrative multidisciplinary discovery platform to unlock marine natural products therapeutic opportunities

Active Project Grant Awarded Last action

Award ID
RM1GM145426
Recipient
Awarding agency
Obligated
$12,377,576

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 85% complete
Place of performance
Gainesville, FL 32611, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
We have assembled an entirely florida-centric collaborative research team with collective expertise in microbial natural products chemistry and pharmacology, genomics, bacterial enzymology, bioinformatics, synthetic biology, chemical synthesis, and cyanobacterial and sponge chemical ecology and phylogenetics. The team is complemented by an out-of-state expert in metagenomics and bioinformatics integration. This geographical cluster of expertise being in the state with the greatest marine biodiversity in the continental US provides a dual benefit and unique opportunity to explore systems that are likely to hold some of the most promise in terms of biosynthetic potential: marine cyanobacterial communities, consisting of benthic filamentous cyanobacteria that are associated with unique microbial diversity, and sponges and their associated rich and unique microbiome in a local hotspot of biodiversity. Compounds produced by these communities are known to cover therapeutically relevant chemical space and are therefore suited as starting points for drug discovery. In a targeted fashion, we will obtain high quality (meta)genome and (meta)transcriptome sequence information from sponge-associated microbiomes and cyanobacteria using state-of-the-art sequencing techniques. We will build an integrated, multi- component platform that leverages existing bioinformatics tools and newly developed artificial intelligence-based tools to shine new light at their genomes with the goal of identifying novel biosynthetic gene clusters, particularly those unattainable with current tools, and even chemical skeletons. We will express natural products encoded by the clusters by employing five types of complementary synthetic biology systems that we have strategically developed over the past several years. These systems originating from five bacterial phyla commonly associated with both marine cyanobacterial and sponge samples cover diverse genetic backgrounds and are expected to effectively translate the identified genetic information of a variety of organisms into chemicals with proper system optimization. We will evaluate and analyze metabolites and expression profiles using LC-MS-based metabolomics and NMR and characterize associated new enzymology. Natural products derived from chemical extract and fraction libraries and those generated through our expression systems or chemical synthesis will be tested in our multidimensional screening platform, consisting of unbiased phenotypic assays in various in vitro and in vivo models as well as experimental and computational target-based functional assays. This approach will enable US to capture a broad array of activities from expressed and unexpressed genes. Selected bioactive natural products will be scaled by chemical synthesis, and bioprobes and enzyme substrates will be prepared for in-depth biological studies and enzymology research, respectively. Successful completion of these aims by our established multidisciplinary investigator team should deliver promising therapeutically important drug leads and tool compounds through thoroughly exploring marine organisms while addressing the current major limitations of natural products drug discovery over the next ten years.

Transactions

Action Obligated Date
Amendment $1,760,984
Amendment $0
Amendment $1,762,990
Amendment $1,758,544
Amendment $1,760,550
Amendment $1,760,550
Amendment $1,786,979
Original award $1,786,979

Subawards

Subrecipient Amount Awarded
Smithsonian Institution This collaborative proposal includes the following elements as a Scope of Work: 1. Coordinating and leading group field trips for purposes of collecting… $726,392
The Trustees Of Princeton University The Donia laboratory at Princeton University will be responsible for two main parts of the proposed work. First, we will perform the computational analysis on… $1,272,288
The Trustees Of Princeton University $254,435
The Trustees Of Princeton University $254,435
Smithsonian Institution This collaborative proposal includes the following elements as a Scope of Work: 1. Coordinating and leading group field trips for purposes of collecting… $435,880
The Trustees Of Princeton University The Donia laboratory at Princeton University will be responsible for two main parts of the proposed work. First, we will perform the computational analysis on… $508,983

Quick answers

Who received award RM1GM145426?

RM1GM145426 was awarded to University Of Florida by National Institute of General Medical Sciences (National Institutes of Health) on August 1, 2022.

How much is award RM1GM145426 worth?

$12,377,576 has been obligated on RM1GM145426.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login