The Patil group uses a combination of modelling, bioinformatics, and experimental approaches to study metabolic networks and how they are controlled.
Previous and current research
Metabolism is a fundamental cellular process that provides molecular building blocks and energy for growth and maintenance. In order to optimise the use of resources and to maximize fitness, cells respond to environmental or genetic perturbations through a highly coordinated regulation of metabolism. Research in the Patil group focuses on understanding the basic principles of operation and regulation of metabolic networks. We are particularly interested in developing models connecting genotype to the metabolic phenotype (metabolic fluxes and metabolite concentrations) in cell factories and in microbial communities.
With a foundation in genome-scale metabolic modelling, optimisation methods and statistics, we develop novel computational algorithms that are driven by mechanistic insights. For example, we have previously shown that the transcriptional changes in metabolic networks are organised around key metabolites that are crucial for responding to the underlying perturbations (see figure).
A microbial community can use the biosynthetic capabilities of its members to decrease the collective dependence on nutritional availability from the environment. The figure illustrates this concept using a toy model (left panel) and shows simulation results for communities of different size assembled from a pool of 1200 species (right panel). The metabolic models used here contain around 1000 reactions per species.
We complement our computational analyses with experimental activities carried out within our group (microbial physiology and genetics) and in close collaboration with other groups at EMBL and elsewhere (high-throughput phenotyping, metabolomics, proteomics etc.). Such combination of computational and experimental approaches has previously enabled us to improve yeast cell factories producing vanillin – a popular flavouring agent. We are currently developing novel tools, concepts and applications in the following research areas:
i) Metabolic interactions in microbial communities: Microbial communities are ubiquitous in nature and have a large impact on ecological processes and human health. A major focus of our current activities is the development of computational and experimental tools for mapping competitive and cooperative metabolic interactions in natural as well as in synthetic microbial communities. With the help of these tools, we aim at uncovering the role of inter-species interactions in shaping the diversity and stability of complex microbial communities.
ii) Computer-aided design of cell factories: Cell factories, such as yeast and CHO cells, are at the heart of biotechnological processes for sustainable production of various chemicals and pharmaceuticals. We are using modelling and bioinformatics tools to identify genetic re-design strategies towards improving the productivity of such cell factories. These strategies guide our experimental implementation, which in turn help us to further improve the design algorithms in an iterative fashion.
Future projects and goals
We are keenly interested in expanding the scope of our computational and experimental models to gain mechanistic insight into the following biological processes: i) xenobiotic metabolism in microbial communities; ii) crosstalk between metabolism and gene regulatory networks; and iii) metabolic changes during developmental processes. To this end, we are actively seeking collaborative projects within EMBL and elsewhere.