Examining the role of transcriptional and epigenetic alterations regulating microcalcification in ductal carcinoma in situ (DCIS)
Dr M Morgan
Dr S Das
Monday, December 02, 2019
Competition Funded PhD Project (Students Worldwide)
Breast cancer is the most common cancer in women worldwide with incidence rates increasing and survival rates largely varying depending on early detection and treatment. Ductal carcinoma in situ (DCIS) is often regarded as a precursor to invasive breast cancer, which is regulated by several genes which possibly control processes involved in development of common features associated with breast cancer such as microcalcification. Our laboratory has shown extensive, despite ongoing research in this specific breast cancer sub-type, the precise cellular/molecular alterations that underpin the DCIS-associated microcalcification remain unknown. This gap in knowledge necessitates an in-depth investigation to identify the genetic/epigenetic alterations that are impacted during the DCIS associated changes such as microcalcification.
The primary aim of this project therefore will be to identify the transcriptional and epigenetic alterations, as well as to examine their precise functional role of these alterations in driving DCIS-associated microcalcification in vitro. To this extent, the project will involve global genomic and DNA methylation analysis using next-generation sequencing based platforms using the well-established pipelines established by our lab of the DCSI cell line models following microcalcification. This will allow identification of gene targets that are altered during the process of microcalcification which will be further examined using in silico methods to identify the molecular/cellular pathways that are impacted by these genes. Next, in vitro perturbation of these gene targets using knock-in and knock-out methods in the DCIS cell lines followed by functional assays in order to ascertain the phenotypic impact of the genes on DCIS-associated phenotype. Ultimately, for the first time this project will allow development of a comprehensive profile of genetic/epigenetic induced alterations that largely impact DCIS associated microcalcification. The functional assessment of these gene targets will thereby identification of potential novel diagnostic/therapeutic targets for DCIS patient.