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Deep single-cell phenotyping to identify governing principles and mechanisms of the subcellular organization of bacterial replication

Project description

Novel phenotyping reveals subcellular organisation without compartmentalisation

Compartmentalisation is a fundamental characteristic of eukaryotic cells. The small membrane-bound organelles including the cell’s control centre with its DNA, the nucleus, and its energy ‘factory’, the mitochondria, provide a means of enhancing the efficiency with which individual functions occur. Unlike eukaryotic cells, bacterial cells lack this compartmentalisation. Despite their ‘simplicity’ as prokaryotic organisms, the mechanisms by which bacteria organise all the processes necessary for their growth and survival are poorly understood. The EU-funded BacterialBlueprint project will use its pioneering high-throughput single-cell phenomics approach for systematic characterisation of phenotypes within and across species to uncover the principles of subcellular organisation of bacterial replication.

Objective

Modern metagenomics has opened our eyes to the immense bacterial diversity that exists both among and within us. Despite this diversity, all bacteria share the basic challenge of organizing the various processes that ensure their faithful replication. All bacterial cells need to metabolize nutrients, generate building blocks, maintain their shape and size, replicate and segregate their chromosomes, synthesize cell walls and membranes, and divide to give rise to daughter cells. At present, we do not understand how bacteria integrate all these processes in their small cellular compartments. What makes this question even more intriguing is that bacteria represent simple forms of proliferating cells, without additional layers of internal organization (e.g. membrane-enclosed organelles) or cell cycle regulation (e.g. cyclins and cyclin-dependent kinases) seen in eukaryotic cells. My goal is to address this gap by uncovering the internal architecture of bacterial replication and identifying the molecular mechanisms that underlie it. I will use a high-throughput single-cell phenomics approach that I developed and that provides high-content, quantitative cell biological information. By applying this approach across different levels of bacterial diversity (both within and across species, beyond the small number of currently existing model species), I aim to identify general and species-specific principles for the subcellular organization of replication in bacteria. This analysis will also enable the identification of key factors involved in establishing these governing principles, which will be functionally characterized further to provide a unique overview of the molecular mechanisms that determine the spatial organization of bacterial replication. If successful, this project will transform our understanding of bacterial cell biology by expanding it beyond current textbook standards and providing us with the blueprints and design principles of bacterial cells.

Host institution

KATHOLIEKE UNIVERSITEIT LEUVEN
Net EU contribution
€ 1 500 000,00
Address
OUDE MARKT 13
3000 Leuven
Belgium

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Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 500 000,00

Beneficiaries (1)