Current key areas of research
1. Emergence and evolution of metabolic excretions and interactions in microbes (funded by NSF/BBSRC) (in collaboration with Wenying ShouLink opens in a new windowLink opens in a new window).
2. Species co-existence and metabolic interactions in spatially organised microbial communities (funded by an investigator award from the Gordon and Betty Moore FoundationLink opens in a new windowLink opens in a new window).
3. Relations between membrane potential, redox cycles, and metabolic fluxes (in-between funding - previously funded by Cancer Research UK).
4. Bistability mechanisms in metabolism (in-between funding) (in collaboration with Elisenda FeliuLink opens in a new windowLink opens in a new window and Alex FletcherLink opens in a new windowLink opens in a new window).
5. Mechanisms of metabolic interactions among soils microbes and plants (in-between funding).
Brief details on our ongoing research
1. Emergence and evolution of metabolic excretions and interactions in microbes (funded by NSF/BBSRC) (in collaboration with Wenying Shou). Metabolic interactions, mediated by excreted metabolites, are shown to be common within the microbial world, as well as between microbes and cells of higher organisms. We would like to understand how metabolic excretions emerge in the first place and how they subsequently evolve into stable interactions. To do so, (i) we develop 'toy' models of key motifs in cell metabolism, focusing on the role of 'cycling' reactions acting as a metabolic flux limitation, and (ii) aim to analyse single-cell physiology under different metabolic perturbations using fluorescent microscopy (using yeast and mammalian cells).
2. Role of spatial organisation on species co-existence and interactions (funded by Gordon and Betty Moore Foundation). Microbes in Nature exist commonly in spatially organised communities. We would like to understand the impact of spatial organisation on species co-existence and species-species interactions (primarily metabolic). To do so, we are using a cyanobacterial model microbial community that is enriched from a freshwater lake and that displays extensive spatial organisation. We are studying the dynamics of spatial organisation in this system, alongside the metabolic interactions and population dynamics.
3. Relations between membrane potential, redox reactions, and metabolic fluxes in cancer cells (previously funded by Cancer Research UK). A commonly disregarded fact about cell physiology is that metabolism implements a flow of electrons from strong electron donors (such as glucose) to strong electron acceptors (such as oxygen and pyruvate). This fact ties the redox reactions within metabolism (e.g. within glycolysis) together with membrane potential, that is ultimately linked to oxidation of the key redox carrier NADH. In this work, we aim to better understand the relation between metabolic pathway fluxes, membrane potential, and redox carrier dynamics. We develop 'toy' models of cell metabolism and membrane potential, and link these with experimental, single-cell data on NADH dynamics and membrane potential. One of our aims is to be able to influence one of these factors to then induce changes in cell physiology.
4. Bistability and oscillation mechanisms in cell metabolism. Key dynamics in metabolism involve oscillations and multiple steady states. To understand the molecular mechanisms that can lead to such dynamics, we develop and study mathematical models of enzymatic reaction motifs.
5. Mechanisms of metabolic interactions among soils microbes and plants. Soil harbours a myriad of microbes, which can interact among each other and with the plant. These interactions determine microbial processes in the soil and impact plant growth. We use the model organisms Bacillus subtilis and Piriforma indica to understand specific interaction mechanisms among soil microbes and their relevance on plant growth (using Arabidopsis thaliana as a model plant).