Appendix D: Confirmation Report

This thesis aims at initiating this framework by building a model of endocrine stimulation of lactation in murine mammary epithelial cells, using information extracted from the literature. At the same time, this project also aims to establish a set of tools necessary for building signal transduction models.

The two main tools needed are,

1. a system for handling and analysis of abstracts from PubMed, which is used to manage the process of extracting, storing and analysis of published abstracts describing the mechanisms of endocrine signal transduction in mammary epithelial cells and the subsequent induction of milk protein genes that are used as a marker for lactation; and
2. a system for the modeling and simulation of the built mouse lactation model, which will be used as a platform for managing the model built from the extracted information and provides facilities for simulation of the model.

The project focuses on two aspects. Firstly, using a published set of 5000 genes that have been implicated in the regulation of murine lactaion, it seeks to understand how they are related to each other, in terms of gene-protein and protein-protein interactions. Secondly, it seeks to explore the link from the endocrine stimulation of the mammary gland by insulin, prolactin, and glucocorticoid to the set of 5000 genes.

Tasks for Second Year

• Complete SBML adaptor for Mosirium
• Run tests cases for SBML conversion to and from MCMAS/MADIR using the test suite provided by SBML Team
• Write a simulation engine for production use
• Examine the routes to add clustering support onto Mosirium
• Extract information from abstracts on prolactin signaling pathways
• Extract information from abstracts on glucocorticoid signaling pathways
• Create a model for insulin/prolactin/glucocorticoid signaling pathways in the mammary gland from hormone receptors to their response elements
• Extract information from abstracts to model the relationships between the set of 5000 genes and their products
• Examine the synergistic use of other text processing tools, such as NLTK, GATE and ConceptNet, on Muscorian
• Write chapter 2 (Mosirium) of thesis
• Write chapter 3 (Muscorian) of thesis

Tasks for Third Year

• Model the relationships (gene-protein, protein-protein) of the 5000 genes and their products
• Link between signal transduction pathways of insulin, prolactin and glucocorticoid, and the interaction model of the set of 5000 genes
• Devise means to verify the model
• Verify the model for accuracy of information
• Write chapter 4 (insulin, prolactin, and glucocorticoid signaling pathways) of thesis
• Write chapter 5 (interactions of 5000-genes and proteins) of thesis
• Write chapter 1 (introduction and literature review of lactation and hormonal signaling in lactation) of thesis
• Write chapter 6 (verification of model) of thesis
• Write chapter 7 (general discussion and future work) of thesis
• Submit PhD thesis

Expected date of completion

Expected date to stop all crucial bench work: 31st December 2006

Expected date of thesis submission: 30th June 2007