Thermodynamic Genome-Scale Metabolic Modeling of Metallodrug Resistance in Colorectal Cancer.

Background: Mass spectrometry-based metabolomics approaches provide an immense opportunity to enhance our understanding of the mechanisms that underpin the cellular reprogramming of cancers. Accurate comparative metabolic profiling of heterogeneous conditions, however, is still a challenge.

Methods: Measuring both intracellular and extracellular metabolite concentrations, we constrain four instances of a thermodynamic genome-scale metabolic model of the HCT116 colorectal carcinoma cell line to compare the metabolic flux profiles of cells that are either sensitive or resistant to ruthenium- or platinum-based treatments with BOLD-100/KP1339 and oxaliplatin, respectively.

A Holistic Approach to Study Photosynthetic Acclimation Responses of Plants to Fluctuating Light.

Plants in natural environments receive light through sunflecks, the duration and distribution of these being highly variable across the day. Consequently, plants need to adjust their photosynthetic processes to avoid photoinhibition and maximize yield. Changes in the composition of the photosynthetic apparatus in response to sustained changes in the environment are referred to as photosynthetic acclimation, a process that involves changes in protein content and composition.

From empirical to theoretical models of light response curves - linking photosynthetic and metabolic acclimation.

Light response curves (LRCs) describe how the rate of photosynthesis varies as a function of light. They provide information on the maximum photosynthetic capacity, quantum yield, light compensation point and leaf radiation use efficiency of leaves. Light response curves are widely used to capture photosynthetic phenotypes in response to changing environmental conditions.

Flux sampling is a powerful tool to study metabolism under changing environmental conditions.

The development of high-throughput 'omic techniques has sparked a rising interest in genome-scale metabolic models, with applications ranging from disease diagnostics to crop adaptation. Efficient and accurate methods are required to analyze large metabolic networks. Flux sampling can be used to explore the feasible flux solutions in metabolic networks by generating probability distributions of steady-state reaction fluxes.

Metabolic acclimation-a key to enhancing photosynthesis in changing environments?

Plants adjust their photosynthetic capacity in response to their environment in a way that optimizes their yield and fitness. There is growing evidence that this acclimation is a response to changes in the leaf metabolome, but the extent to which these are linked and how this is optimized remain poorly understood. Using as an example the metabolic perturbations occurring in response to cold, we define the different stages required for acclimation, discuss the evidence for a metabolic temperature sensor, and suggest further work towards designing climate-smart crops.