Life Sciences & Biotechnology
Title : | Influence of inherent tissue mechanics and cellular heterogeneity on epithelial defence against cancer |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Medhavi Vishwakarma, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | medhavi@iisc.ac.in |
Equipments : | Real Time PCR |
Details
Executive Summary : | Epithelial Defence against Cancer (EDAC) is a defense mechanism in epithelia that eliminates oncogenic cells through cell competition. However, EDAC is impaired when oncogenic cells become fitter than the host, leading to cancer initiation. Aging is a pro-tumorigenic state and is the single most important risk factor for cancer development in epithelial tissues. This project aims to understand how EDAC is impaired as tissue ages, hypothesizing that ageing phenotypes, such as increased transcriptional noise and changing tissue mechanics, might act as regulating factors for epithelial defense against cancer. Using mammary breast epithelia as a model system, the researchers will study tissue heterogeneity as a regulator of EDAC. They will measure biochemical heterogeneity in 2D cultures of MCF10a cells and physical heterogeneity using techniques like live confocal microscopy, real-time PCR, immunostaining, and flow cytometry. They will transform healthy cells into fluorescently tagged oncogenic mutants overexpressing ErbB2, which will influence the fate of oncogenic mutants. The researchers aim to mimic ageing by overexpressing integrin b3 and reducing cell-cell adhesions, modulating tissue mechanics. This study will provide insight into why aged epithelial tissue might be more vulnerable to cancer and help identify treatment strategies exploiting host defense mechanisms against cancer. |
Total Budget (INR): | 32,14,220 |
Organizations involved