Research

Current key areas of research

1. Cellular metabolism: Role of co-substrate dynamics in regulating fluxes (funded by Leverhulme) (in collaboration with Wenying ShouLink opens in a new windowLink opens in a new window).

2. Microbial communities: 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 window).

3. Gliding motility in cyanobacteria and its role in macro scale microbial organisation

4. Relations between membrane potential, redox cycles, and metabolic fluxes (previously funded by Cancer Research UK).

5. Bistability and oscillation mechanisms in reaction networks (in collaboration with Elisenda FeliuLink opens in a new windowLink opens in a new window and Alex FletcherLink opens in a new window).

Brief details on our ongoing research

1. Regulation of metabolic fluxes via co-substrate dynamics (Leverhulme grant, previously funded by NSF/BBSRC) (in collaboration with Wenying Shou). In recent modelling work, we showed that dynamics of co-substrates (such as NADH) can create “built-in” regulation of metabolic fluxes. We are experimentally verifying this theory in yeast (Crabtree effect) and will expand to mammalian cells (Warburg effect). Expansion of this theory will allow engineering of metabolic fluxes via control of co-substrate dynamics (either by genetic or electrochemical means).

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 use laboratory adaptation under carbon-free media to develop cyanobacteria-dominated, simplified communities. We use these communities to answer questions on community assembly and stability, as well as understanding microbial interactions. This work paves the road to AI-assisted community assembly and engineering of bespoke communities for biotechnology applications.

3. Gliding motility in filamentous cyanobacteria. Gliding motility is seen in many single-celled bacteria, as well as in multicellular, filamentous cyanobacteria. Currently, the molecular mechanisms underpinning this type of motility are still unclear. We study both the dynamics of gliding motility and its relation to macro scale structure formation, using model filamentous cyanobacteria Fluctiforma draycotensis.

4. Relations between membrane potential, redox reactions, and metabolic fluxes (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.

5. 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.