Deciphering and Engineering the overlooked but Universal phenomenon of Subpopulations in BIOtechnology

Microbial bioproduction, despite being considered a paradigmatic sustainable alternative to petroleum-based chemistry, is often limited by low yields and productivities, which prevents commercialisation.

It is generally known for all types of cells that genetically identical populations can form metabolically distinct subpopulations.

This diversity strongly impairs bioproduction as the presence of low-producer or slow-grower cells reduces overall yields.

However, the universal phenomenon of subpopulations emergence has been largely overlooked, especially in biotechnology, due to technical difficulties.

Now, thanks to recent developments in single cell technologies, in molecular understanding of microbial communities and in synthetic biology tools, we can begin to address this widespread and impactful biological feature.

I propose to explore the emergence of subpopulations in yeast and understand their implications in metabolism and bioproduction using and developing cutting edge synthetic biology tools.

I aim to use that knowledge to develop novel engineered strains that lack the presence of undesired subpopulations and then use such homogeneous populations for bioproduction. The homogenised production will be investigated in both, monocultures and microbial communities.

In DEUSBIO, I will set up an innovative framework to maximise the biosynthesis of high value molecules, with high potential to overcome current limitations.This project will shed light on the phenomenon of subpopulations, whose relevance goes beyond bioproduction, as for example, it has been associated with the origin of multicellularity.

Increasing our knowledge about this matter will also have implications in biomedicine, as cell subpopulations are extremely important in the appearance of antimicrobial resistant, in cancer heterogeneity, and in microbiome complexity.