Periodic Reporting for period 2 - DEUSBIO (Deciphering and Engineering the overlooked but Universal phenomenon of Subpopulations in BIOtechnology)
Période du rapport: 2022-09-01 au 2024-02-29
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:
a. To identify the main types of subpopulations of yeast in different growth conditions.
b. To study the specific areas in the yeast genome responsible for the emergence of specific subpopulations.
c. To engineer a homogenised yeast population with enhanced bioproduction capacities
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:
a. To identify the main types of subpopulations of yeast in different growth conditions.
b. To study the specific areas in the yeast genome responsible for the emergence of specific subpopulations.
c. To engineer a homogenised yeast population with enhanced bioproduction capacities
UP to now, we conducted the work according to the project plan and timeline.
We generated a catalogue of transcriptional subpopulation in yeast and a library of strains with different subpopulations marked with fluorescence reporters. We identified the mechanisms involved in the emergence of subpopulations.
Now we are working on engineering yeasts to produce homogeneous cells to increase yield in bioproduction.
Each of our finding and achievements are now in preparation for publications in leading scientific journals (some of them already published).
We generated a catalogue of transcriptional subpopulation in yeast and a library of strains with different subpopulations marked with fluorescence reporters. We identified the mechanisms involved in the emergence of subpopulations.
Now we are working on engineering yeasts to produce homogeneous cells to increase yield in bioproduction.
Each of our finding and achievements are now in preparation for publications in leading scientific journals (some of them already published).
By the end of the project, we will have a homogenised best-in-class yeast population created at the lab for the first time.
We will explore the effects of natural community behaviours on molecular expression pathways and find the features that will lead to the best production yield strain.
Once we create a homogenised yeast population, we will engineer the strains in order to produce high value molecules.
The project outcomes will be published either in journals with interest in bioproduction, microbial communities and synthetic biology such as Nature Biotechnology, Metabolic Engineering, Nature Microbiology. These results will be presented in the Gordon Conference in Synthetic Biology, the major conference in the field, which takes places every two years in the USA.
We will explore the effects of natural community behaviours on molecular expression pathways and find the features that will lead to the best production yield strain.
Once we create a homogenised yeast population, we will engineer the strains in order to produce high value molecules.
The project outcomes will be published either in journals with interest in bioproduction, microbial communities and synthetic biology such as Nature Biotechnology, Metabolic Engineering, Nature Microbiology. These results will be presented in the Gordon Conference in Synthetic Biology, the major conference in the field, which takes places every two years in the USA.