Life Sciences & Biotechnology
Title : | Understanding the sources and consequence of heterogeneity in endocytic capacity in mammalian cells |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Varadharajan Sundaramurthy, National Centre For Biological Sciences, Karnataka |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | varadha@ncbs.res.in |
Details
Executive Summary : | Phenotypic heterogeneity in isogenic cultures is a significant factor in determining population outcomes, particularly during intracellular infections. This is particularly relevant as an infected cell population contains individual cells with distinct outcomes. Understanding the sources of heterogeneity is crucial to addressing this issue. Previous research has shown that the variance in the endocytic capacity of macrophages determines phagocytosis, infectivity, and sub-cellular trafficking of pathogens like M. tuberculosis. The study aims to understand the source of endocytic variance, quantitatively analyze the variance of endocytic states, and assess the role of endocytic variance in generating phenotypic diversity in intracellular M. tuberculosis (Mtb). The study will employ single cell readouts (flow cytometry and long-term live cell imaging) to understand the stability of the states over time. The hypothesis is that the states fluctuate over the cell cycle, and experiments will be performed using flow sorted populations of cells with different endocytic capacities to identify molecular and cellular determinants of these alterations. The study will further our understanding of the role of cell-to-cell variability in non-perturbed populations at three key levels. First, the experiments will identify key determinants of variation, providing a mechanism on the determinants of cellular heterogeneity in endocytic capacity. Second, the detailed quantitative experiments will provide a comprehensive understanding of the cell-to-cell variability of endocytic capacity, examining the endocytic state(s) at a single cell level over time. Finally, the experiments will link the cell-to-cell variability in endocytic capacity to observed phenotypic diversity in Mtb infections, providing a rationale for host-directed modulation of tolerance. |
Total Budget (INR): | 56,19,628 |
Organizations involved