A Genome-scale models of metabolism and protein expression can be reconstructed for microbes
B Microbial stress responses are reconstructed from molecular mechanisms
C These models can help discover new antimicrobials
Aerobic organisms have evolved cellular responses against reactive oxygen species (ROS) over the coures of 3 billion years, since the Earth's atmosphere became oxygenated. ROS targets macromolecules and metal cofactors, which can impair cellular function. ROS is generated as a by-product of normal metabolic operation. It is also used as an offensive tool by competing microbes and the human immune system.
Adaptation against ROS stress can require system-level responses, including metabolic shifts, use of alternative cofactors, and change in macromolecular composition. Adaptation against other stresses (e.g., thermal, pH, osmotic) requires similar system level responses.
Such system-level stress responses can be modeled using genome-scale models that integrate the processes of metabolism and macromolecule expression (ME models). By extending these models with the thermodynamic and kinetic processes associated with stress-related damage and repair of cellular components, it is possible to model microbial stress response. These extended models are collectively termed StressME models.
Our lab aims to: