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Reassessing Bacterial Cell Cycle Regulation: Revealing Novel Regulatory Principles in Realistic Environments

Project description

Fighting antibiotic resistance with new insights into bacterial growth

Antibiotic resistance is becoming one of the biggest health threats of our time. It is expected to cause more deaths each year than COVID-19 or cancer. Despite this, efforts to address the issue remain insufficient. To combat this, a deeper understanding of bacterial growth is crucial. In this context, the ERC-funded REalCYCLE project aims to investigate the cell cycle of Streptococcus pneumoniae, a major human pathogen, under clinically relevant stresses. By applying an innovative FACS-seq approach, the project will uncover overlooked regulatory mechanisms, providing key insights into bacterial behaviour outside optimal lab conditions. These findings could pave the way for novel antimicrobial therapies to combat antibiotic resistance.

Objective

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.

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.

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.

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. After identifying the selected mutants, I will characterize the molecular mechanisms involved and investigate their level of conservation.

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.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

UNIVERSITE CATHOLIQUE DE LOUVAIN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 926,00
Address
PLACE DE L UNIVERSITE 1
1348 LOUVAIN LA NEUVE
Belgium

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Region
Région wallonne Prov. Brabant Wallon Arr. Nivelles
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 926,00

Beneficiaries (1)

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