Model-driven engineering of central metabolism

Cellular metabolism underpins life. In addition to its central role as the energy provider, metabolism also provides the cell its building materials. It is thus no surprise that engineering of cellular metabolism is one of the key targets of synthetic biology efforts. Despite significant amount of work in this area, however, rational engineering of metabolism is still not achieved and trial-and-error and “intuitive reasoning” guide most studies. This is mostly due to a lack clear understanding of metabolic structures and functions in the cells. For example, even the most central structures in metabolism, such as the TCA cycle are not appropriately modelled. Similarly, phenomena such as the overflow metabolism, in which key fluxes are diverted away from TCA cycle into fermentation products, still remain paradoxical.
In Soyer lab, we are interested in developing quantitative and evolutionarily motivated approaches to the study of cellular metabolism. While metabolism fulfills many functions in the cells, these functions could not have been a priori drivers of the evolution of metabolism1. The most important drivers must have come even before cells and specific functions, and are most likely to have involved thermodynamic forces2-4. These thermodynamics drivers, along with cellular trade-offs, might still play important roles in the current functions and dynamics of metabolic systems5-8.
In this particular project, the successful candidate will join our ongoing efforts to decipher cellular metabolism and study the basis and consequences of overflow metabolism within key model organisms that are also of biotechnological relevance. In particular, we will aim to quantify overflow metabolism at population and single cell levels using the model species from the kingdom of algae, yeast, and bacteria. We have several species from each kingdom established in our own (and collaborators’) laboratories and have been developing key measurement and quantitative imaging approaches. The successful candidate will use this base to further develop quantitative measurement of cell metabolism and overflows. S/he will then use this data in conjunction with mathematical models to devise rational engineering routes for genetic manipulations. In parallel, the successful candidate will develop synthetic co-cultures that will allow exploiting of overflow metabolism, and thereby achieve higher productivity from the key organisms studied.


Key experimental skills involved: Microbial skills in culturing, isolation. Microscopy skills in time laps microscopy. Data analysis skills. Mathematical modelling skills.