Reassessing Bacterial Cell Cycle Regulation: Revealing Novel Regulatory Principles in Realistic Environments
This project aims to investigate the bacterial cell cycle of Streptococcus pneumoniae under clinically relevant stresses to identify new antimicrobial targets against antibiotic resistance.
Projectdetails
Introduction
Antibiotic resistance is quickly becoming one of the greatest healthcare challenges of our time. It is soon expected to claim more lives annually than the COVID-19 pandemic or cancer. Yet, the urgency of this problem is not reflected in our efforts to solve it.
Background
Because blocking bacterial growth is key in treating disease, greater insight into the bacterial cell cycle is needed. Currently, the bacterial cell cycle is primarily studied under optimal lab conditions. This is equivalent to studying the behaviour of an animal kept prisoner in a zoo. Although valuable observations can be made, essential information will be missed.
Research Objective
To obtain a more accurate view of bacterial growth, I will investigate the cell cycle of the major human pathogen Streptococcus pneumoniae while applying clinically relevant stresses. Based on my first-hand experience with the S. pneumoniae cell cycle, I hypothesize that many cell cycle regulatory mechanisms have been overlooked thus far because of their relatively low importance in optimal growth conditions, which are rarely encountered in reality.
Methodology
I will identify genes involved in such cell cycle regulatory mechanisms at a genome-wide scale using an innovative approach I developed for this purpose. In contrast to fitness-based nonspecific read-outs, I will perform FACS-seq (fluorescence-activated cell sorting-based sequencing) to select mutants in which specific cell cycle processes are altered based on appropriate fluorescent read-outs.
- Identify selected mutants.
- Characterize the molecular mechanisms involved.
- Investigate their level of conservation.
Expected Outcomes
My research will substantially advance our understanding of how bacteria regulate their cell cycle when exposed to real-life stresses. My results can therefore provide a starting point for the development of new antimicrobial therapies that target mechanisms important for growth in vivo. Given the emerging antibiotic resistance crisis, such efforts are urgently needed.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 1.499.926 |
Totale projectbegroting | € 1.499.926 |
Tijdlijn
Startdatum | 1-1-2025 |
Einddatum | 31-12-2029 |
Subsidiejaar | 2025 |
Partners & Locaties
Projectpartners
- UNIVERSITE CATHOLIQUE DE LOUVAINpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
Finding the missing links in the bacterial cell cycleThis project aims to uncover the connections between key bacterial cell cycle events to inform innovative antibiotic discovery methods targeting multiple pathways. | ERC Advanced... | € 2.999.625 | 2024 | Details |
Breaking resistance of pathogenic bacteria by chemical dysregulationThe project aims to combat antibiotic-resistant bacteria by developing innovative small molecules that dysregulate bacterial physiology through a three-tiered chemical strategy. | ERC Advanced... | € 2.499.785 | 2023 | Details |
Visualizing microbial societies: exposing the principles of single-cell phenotypic heterogeneity via massively multiplexed imagingThis project aims to systematically explore phenotypic variation in Pseudomonas species using single-cell transcriptomics to understand microbial resilience, social interactions, and infection dynamics. | ERC Starting... | € 1.499.084 | 2024 | Details |
Revealing second messenger functions in bacterial stress response, cell differentiation and natural product biosynthesisThis project aims to explore c-di-AMP functions in Streptomyces to uncover new bacterial signaling principles and identify potential antibiotic targets and biosynthesis triggers. | ERC Starting... | € 1.478.373 | 2022 | Details |
Unraveling the regulatory networks in Streptomyces that switch on antibiotic production on demandThis project aims to unlock the expression of cryptic biosynthetic gene clusters in Streptomyces to enhance drug discovery and agricultural applications through innovative systems biology and ecological insights. | ERC Advanced... | € 3.343.206 | 2022 | Details |
Finding the missing links in the bacterial cell cycle
This project aims to uncover the connections between key bacterial cell cycle events to inform innovative antibiotic discovery methods targeting multiple pathways.
Breaking resistance of pathogenic bacteria by chemical dysregulation
The project aims to combat antibiotic-resistant bacteria by developing innovative small molecules that dysregulate bacterial physiology through a three-tiered chemical strategy.
Visualizing microbial societies: exposing the principles of single-cell phenotypic heterogeneity via massively multiplexed imaging
This project aims to systematically explore phenotypic variation in Pseudomonas species using single-cell transcriptomics to understand microbial resilience, social interactions, and infection dynamics.
Revealing second messenger functions in bacterial stress response, cell differentiation and natural product biosynthesis
This project aims to explore c-di-AMP functions in Streptomyces to uncover new bacterial signaling principles and identify potential antibiotic targets and biosynthesis triggers.
Unraveling the regulatory networks in Streptomyces that switch on antibiotic production on demand
This project aims to unlock the expression of cryptic biosynthetic gene clusters in Streptomyces to enhance drug discovery and agricultural applications through innovative systems biology and ecological insights.