Endocrine Abstracts

Glucocorticoid hormones are used in the treatment of variety of diseases, due to their diverse range of effects. Acute lymphoblastic leukaemia (ALL), the most common form of childhood cancer, is one such disease treated by glucocorticoids (GCs). Although there has been much success in the treatment of ALL with GCs, drug resistance remains a problem, despite the detailed knowledge of the signalling networks underlying the GC actions through the glucocorticoid receptor (GR). Systems biology offers the opportunity to gain a holistic view of protein interaction networks, whilst also allowing for the generation of predictions through in silico knockouts which can be validated through conventional laboratory approaches. Systems biology has shown great success in identifying the functions of seemingly-redundant proteins. Here we present the beginnings of a model of the GR interactome, constructed through MATLAB using the add-on CellNetAnalyzer, and visualised through Cytoscape. The model currently consists of proteins that interact with the GR and interactions between these proteins. Protein interactions were extracted automatically from the STRING database using a Java program, and then manually curated by literature mining to remove false positives. The curated interactions were imported into CellNetAnalyzer. Future work will be directed towards expanding and connecting this model to drugs or processes like apoptosis, to detecting potential therapeutic targets, whilst also validating it through analysis of microarray data from ALL patients, paving the way for personalized treatment.