Welcome to the In-Silico Model of Cutaneous Lipids Wiki

About the Project

The skin is the largest structure in the body and acts as the ultimate barrier to our environment. The aim of this project is to comprehend how the lipid network within the skin responds in physiopathological states such as inflammation (sunburn, atopic dermatitis, psoriasis). Little is known about the regulatory relationships within the cutaneous lipid signalling networks, and there is a distinct lack of information about how these networks interact between compartments (the different layers of the skin).

Description of the Model

We aim to create a quantitative computational model of the cutaneous lipid signalling networks, including variables such as multiple lipid substrates and enzyme isoforms. Model construction will be guided by literature studies, combined with new experimental lipidomics data collected in this project. In order to analyse model properties, experimental studies such as altering the systemic availability of fatty acids and the effect upon the anti-inflammatory milieu will be measured. This information will be integrated into the model to obtain estimated kinetic parameter values and also to validate and refine the overall model topology. The resulting mathematical model will be testable and predictive of the lipid responses during inflammation. The insights obtained will allow for more targeted experiments to be designed in order to better understand skin lipid biology and to aid in the mapping of lipid networks contributing to inflammation. This will ultimately support the design of interventional studies to combat skin disease.

Species

Acronym	Name	Species Type
15-D-PGJ2	15-Deoxy-Cyclopentenone Prostaglandin	Chemical
6-K-PGF2α	6-Keto-Prostaglandin F2α	Chemical
AA	Arachidonic Acid	Chemical
COX	Cycloxygenase	Enzyme
FA	Fatty Acid	Chemical
LOX	Lipoxygenase	Enzyme
PGD2	Prostaglandin D2	Chemical
PGDS	Prostaglandin D Synthase	Enzyme
PGE2	Prostaglandin E2	Chemical
PGES	Prostaglandin E Synthase	Enzyme
PGF2α	Prostaglandin F2α	Chemical
PGFS	Prostaglandin F Synthase	Enzyme
PGH2	Prostaglandin H2	Chemical
PGI2	Prostaglandin I2	Chemical
PGJ2	Cyclopentenone Prostaglandin J2	Chemical
PLA2	Phospholipase A2	Enzyme
TXA2	Thromboxane A2	Chemical
TXB2	Thromboxane B2	Chemical
TXAS	Thromboxane A Synthase	Enzyme

Information on the initial concentrations of all species can be found here.

Reactions

The reactions per compartment are the following:

Cell Binding of R2 to OR operator Binding of R2 to OA operator Binding of R2 to A Binding of R2 to C Binding of A-R2 to OA' operator Synthesis of C Transcription of r Transcription of a Antisense interaction between r and a Translation of R Translation of A

Formation of homo-dimer R2 Degradation of r Degradation of R Degradation of R2 Degradation of a Degradation of A Degradation of C Degradation of C2-R2 Degradation of A-R2 Degradation of r-a Cellular growth