The project was designed to address the phenomenon of microbial subpopulation in the context of bioproduction. Defined subpopulations emerging from genetically identical cells have been found across all forms of life, including microorganisms. Understanding microbial subpopulations has great importance in a variety of fields for example biomedicine in antimicrobial resistance research or environmental microbiome. Here we are focusing on bioproduction, where the appearance of low-producing and slow-growing cells limit overall yields and productivities. Addressing this issue would enable the creation of more profitable bioprocess, which is key to develop a bio-based economy. Despite their biological and biotechnological relevance, this universal phenomenon has not been largely overlooked in part due to technical limitations arising from using single cell methodologies and analysis tools. Only recently, latest developments of robust single cell sequencing techniques have been developed, which can be now employed to study microbial subpopulations. Such advances, together with the blooming of synthetic biology tools that we and others have developed to facilitate strain engineering, make this project timely.
This ambitions project will have a high impact in both fundamental and industrial research and could challenge our current conception of clonal populations. The global economy faces many societal challenges, including dealing with climate change, a growing population to be fed and kept healthy and an unsustainable dependence on non-renewable resources. The current manufacturing of most chemicals, energy, materials, and consumer products relies on the exploitation of fossil fuels, which are non-renewable and limited. It is therefore urgent to find new production technologies, utilising renewable sources, such as those provided by Industrial Biotechnology. Microbial-based bioproduction can convert low-cost substrates into chemicals, materials, or fuels in an eco-friendly manner. Despite the advantages offered by microbial biotechnology, few bioprocesses have reached the market due to high production costs and low yields.
The overall objectives of the DEUSBIO project are:
1. Identify the main types of subpopulations that emerge in yeast under different growth and production conditions.
2. Develop tools to monitor and characterize heterogeneity at the single-cell level.
3. Uncover the genetic determinants—specific genomic regions and regulators—responsible for the formation of these subpopulations.
4. Engineer more homogeneous yeast populations with enhanced and consistent bioproduction capacities
5. Explore community-based strategies (e.g. division of labour) to reduce cell stress that can lead to heterogeneity.
