The control of sporulation and antibiotic production through c-DI-GMP signaling

Active Project Grant Awarded Last action

Award ID
R35GM156858
Recipient
Awarding agency
Obligated
$1,879,819

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 36% complete
Place of performance
Ithaca, NY 14853, USA

Award details come from USAspending.gov.

Description

Abstract
In all domains of life, cells must employ tightly controlled mechanisms to regulate global processes in response to environmental inputs. In bacteria, signaling through the nucleotide second messenger 3',5'-cyclic diguanylic acid (c-DI-GMP) is one of the most conserved mechanisms cells use to trigger lifestyle changes in response to specific environmental cues. Although the enzymes that synthesize and degrade c-DI-GMP can be found in all bacterial phyla, studies of this second messenger have focused on model species belonging to the phylum pseudomonadota. A key knowledge GAP is understanding how this fundamental mechanism governs regulation of gene expression in diverse bacterial phyla. This project will address this by characterizing the molecular mechanisms and evolution of c-DI-GMP signaling in the antibiotic-producing bacterial genus streptomyces, which belongs to phylum actinobacteria (synonym actinomycetota). In streptomyces, c-DI-GMP is the central integrator controlling a highly unusual life cycle that involves progression from vegetative growth to production of reproductive aerial hyphae that differentiate into chains of spores. To investigate the molecular basis and functional diversification of c-DI-GMP signaling, this project will focus on three areas: (1) the mechanisms through which c-DI-GMP regulates progression through the developmental life cycle in the model species streptomyces venezuelae; (2) the evolution and distribution of conserved components of c-DI-GMP signaling networks; and (3) the impact of c-DI-GMP on antibiotic biosynthesis, which is tightly controlled along with the developmental life cycle, in diverse antibiotic-producing actinobacterial species. These studies will contribute to a fundamental understanding of how bacterial control gene expression and will leverage this knowledge to manipulate antibiotic production.

Transactions

Action Obligated Date
Amendment $38,347
Amendment $345,117
Amendment $345,117
Amendment $383,746
Amendment $383,746
Original award $383,746

Quick answers

Who received award R35GM156858?

R35GM156858 was awarded to Cornell University by National Institute of General Medical Sciences (National Institutes of Health) on January 1, 2025.

How much is award R35GM156858 worth?

$1,879,819 has been obligated on R35GM156858.

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