OncoLive | Optogenetic control and measurement of oncogenic mutations and signaling in organoid cultures for the biophysical modelling of early oncogenesis.
What is it? OncoLive is a Cancer Research UK funded multi-disciplinary collaboration between Dr. Alessandro Esposito (MRC Cancer Unit – University of Cambridge), Dr. Maria Alcolea (Stem Cell Institute – University of Cambridge) and Dr. Philip Greulich (Mathematical Sciences – University of Southampton).
What is oncogenesis? Oncogenesis, also called carcinogenesis or tumorigenesis, is the process of transformation of cells into cancer. Our bodies are made of cells and cells maintain the structure and function of tissues and organs by establishing a balance between cell proliferation and cell death. This balance is called ’tissue homeostasis’ and it is maintained by rules written in our DNA and cell-to-cell interactions. Environmental factors and errors that can occur by chance during the normal living of a cell can damage (mutate) DNA, change how cells communicate and break the rules. If not cleared by tumor-suppressive mechanisms, mutant cells will develop to a clinically relevant cancer over time.
What is optogenetics? Optogenetics is a very recent research field aimed to harness the power of biophotonics and genetic engineering. In broad terms, optogenetics includes research in and application of genetically encoded tools that permits scientists to manipulate the behaviour of a cell or an organism by light. Optogenetics can provide high spatiotemporal control of cell biochemistry through the use of light-inducible ion channels or protein-protein interactions.
What is light sheet fluorescence microscopy? Light sheet fluorescence microscopy (LSFM) is an optical technique that permits scientists to image three-dimensional samples with high spatiotemporal resolution and low invasiveness. Because of these features, LSFM has been extensively utilized in developmental biology to understand how entire organisms develop from a fertilized egg.
What are we doing? We aim to remove technology barriers that are limiting our understanding of the earliest steps in oncogenesis by integrating advanced photonics, genetic, culturing and biophysical modelling techniques. In broad terms, we will attempt to develop a unique LSFM capable of controlling and quantifying biochemical events in 3D organoids, seeding at a given time and in spatially localized regions oncogenic mutations, for then following how different mutant cells cooperate or compete. These techniques will be exploited to generate models of early oncogenesis for oesophageal cancer.