Overview of the research programme
We will use a synthetic biology driven approach to generate a suite of production circuits (for EPS, vitamins and carotenoids) that work in both E. coli and S. cerevisiae and across settings, from the laboratory to industry. To achieve our objectives, we have assembled a network of leading scientists with complementary expertise covering a broad range of disciplines, including quantitative biology and cell biophysics, cell engineering and microbial physiology. Our approach is augmented and intertwined with whole-cell mathematical modelling that will ultimately allow prediction of contextual effects between circuits and the host organism.
We will develop a creative research environment for inter-disciplinary and inter-sectoral training of the ESRs with a broad range of industrial stakeholders. The research is embedded in four Research Training work packages (WPs) where, together, the ESRs working on individual research projects relevant for each RO mentioned above:
(i) to construct and optimise various synthetic circuits with differing complexities for applications in both E. coli and S. cerevisiae,
(ii) to analyse physiological changes and response of the host upon expression of these circuits, and
(iii) to exploit the flexibility of central cellular processes
(iv) to reprogram and optimize the hosts for optimal industrial production.
It is our strength that we use two model organisms, two established and attractive industrial platforms, and take advantage of the natural scale-up in complexity from E. coli to S. cerevisiae to more robustly develop mathematical models that describe production circuits across species. The research programme will use novel technologies that have a cell-wide resolution to simultaneously measure the metabolome and transcriptome and to globally profile translation and lipid composition with an unprecedented depth. Furthermore, these data will be integrated with microscopy approaches with high spatio-temporal resolution to assess the physico-chemical properties of the cell. We will leverage the unique features of each host (e.g. the fast growth and small genome of E. coli, and the growth robustness and infection-free growth at low pH of S. cerevisiae) to create robust industrial circuit production hosts.
Our ESRs will gain expertise in the systems and production behaviour of bacteria and lower eukaryotes, which will equip them with unique skills by applying evolutionarily-conserved principles to work with organisms from different kingdoms.
The SynCrop Network is built around a strong core of partners with an established collaboration in research and the successful training of young researchers in other consortia (e.g. NICHE; ISOLATE; METACODE; FOR1805) or on a bilateral basis substantiated with several joint publications. These established connections help minimise risk. All projects can start immediately from the onset of the funding period and successful recruitment: some synthetic circuits have already been constructed and initial versions of the biosensors are available to quantify, for example, pH, ionic strength, macromolecular crowding and energy charge. SynCrop partners work at the frontiers of their fields and contribute to the development of high-resolution technologies providing a powerful toolkit for the ESRs. Milestones have been defined to maximise the possibilities of breakthroughs through cooperation between the ESRs and partners. Different parts of the program are connected through intimate collaboration. To maximise collaboration between ESRs, their individual research projects are connected, but in such way to facilitate complementarity and avoid critical interdependencies that could jeopardize the training due to delays in another project.
By close collaboration between academia and industry, through cutting-edge research, diverse training courses and secondments, SynCrop will provide an inter-disciplinary personal development and training programme for each ESR that complements their research experiences. Furthermore, the trans-national mobility is designed to improve the employability of our ESRs and enhance their future career perspectives.