Hadrien delattre- University of Warwick
Hadrien delattre
- University of Warwick
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14
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Publications (14)
The fluorescent benzothiazole dye thioflavin T (ThT) is widely used as a marker for protein aggregates, most commonly in the context of neurodegenerative disease research and diagnosis. Recently, this same dye was shown to indicate membrane potential in bacteria due to its cationic nature. This finding prompted a question whether ThT fluorescence i...
Cycling of co-substrates, whereby a metabolite is converted among alternate forms via different reactions, is ubiquitous in metabolism. Several cycled co-substrates are well known as energy and electron carriers (e.g. ATP and NAD(P)H), but there are also other metabolites that act as cycled co-substrates in different parts of central metabolism. He...
Cycling of co-substrates, whereby a metabolite is converted among alternate forms via different reactions, is ubiquitous in metabolism. Several cycled co-substrates are well known as energy and electron carriers (e.g. ATP and NAD(P)H), but there are also other metabolites that act as cycled co-substrates in different parts of central metabolism. He...
The fluorescent benzothiazole Thioflavin T (ThT) has a high binding affinity to protein aggregates and is used as a marker for the study of this process, most commonly in the context of neurodegenerative disease research and diagnosis. Recently, this same dye was shown to indicate membrane potential in bacteria due to its cationic nature. This find...
Cellular metabolism consists of many interconnected reactions that present feedbacks through cyclic reaction motifs and through metabolite regulation of enzyme kinetics. In addition, metabolism is interlinked with gene regulation and other cellular, energy-driven processes such as division and motility. While many important insights have been gaine...
Viruses rely on their host for reproduction. Here, we made use of genomic and structural information to create a biomass function capturing the amino and nucleic acid requirements of SARS-CoV-2. Incorporating this biomass function into a stoichiometric metabolic model of the human lung cell and applying metabolic flux balance analysis, we identifie...
Microbial communities are complex dynamical systems harbouring many species interacting together to implement higher-level functions. Among these higher-level functions, conversion of organic matter into simpler building blocks by microbial communities underpins biogeochemical cycles and animal and plant nutrition, and is exploited in biotechnology...
Microbial communities are complex dynamical systems harbouring many species interacting together to implement higher-level functions. Among these higher-level functions, conversion of organic matter into simpler building blocks by microbial communities underpins biogeochemical cycles and animal and plant nutrition, and is exploited in biotechnology...
Microbial communities are key engines that drive earth’s biogeochemical cycles. However, existing ecosystem models have only limited ability to predict microbial dynamics and require the calibration of multiple population-specific empirical equations. In contrast, we build on a new kinetic “Microbial Transition State” (MTS) theory of growth derived...
Microbial communities play a key role in geochemical cycles and environmental bioprocesses. Despite their importance, the mechanisms involved in their structuration remain elusive and are poorly captured in current models. The modelling approach developed during this thesis stands as an alternative to the current empirical approaches. It relies on...
Distant homology search tools are of great help to predict viral protein functions. However, due to the lack of profile databases dedicated to viruses, they can lack sensitivity. We constructed HMM profiles for more than 80,000 proteins from both phages and archaeal viruses, and performed all pairwise comparisons with HHsearch program. The whole re...
Questions
Questions (2)
NAD+ has a -1 net charge while NADH has a -2 net charge (https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide). But in total, 7 different ionization states have been reported for that molecule (http://equilibrator.weizmann.ac.il/metabolite?compoundId=C00003).
Experiments and models about NAD+/NADH generally only account for its "-1" and "-2" state. In order to be able to formulate the energy differential associated with this conserved moiety as a function of ionic strength, pH, pMg etc, the speciation of this molecule and its interaction with metal ions must be studied (as it has been made and taken into account in studies of ATP, for example in Iotti et al. 2005 (doi: 10.1016/j.bbabio.2005.01.008) and Vinnakota et al. 2006 (doi: 10.1529/biophysj.105.073296)). Has such work ever been done for the NAD molecule?
As an example, let us consider the acetoclastic methanogenesis reaction, mediated by a microbial population in its culture medium;
C2H3O2- + 4 H2 + H+ --> 2 H2O + 2 CH4
In order to compute the Gibbs energy differential of this reaction in standard conditions, one has to sum the Gibbs energy of formation of each reagent, multiplied by their stoichiometric coefficient (negative if consummed).
The Gibbs energy of formation of H2 and CH4 differs depending on whether they are assumed to be in gas or dissolved form. This significantly affects the computed value of the Gibbs energy of the reaction. This is especially concerning when modelling anaerobic metabolisms, where the dG of all reactions are usually small and close to eachothers, so a small change of a dG can totally change the predictions.
Has this question been investigated, and what is the rationale behind the choice of gas or dissolved form in a metabolic reaction?
In the literature, it is often assumed that those molecules are in gas phase, but I suspect that it is because those papers are based on the Gibbs energy tables of Thauer (Thauer et al., Bacteriol Rev. 1977 Mar;41(1):100-80), which generally does not provide Gibbs energy of formation for molecules in dissolved form.
