Optogenetic stem cells in heterotypic tumor spheroids

With approximately 1.2 million new cases and 600,000 deaths reported each year, colorectal cancer is the third most common form of the disease, and the fourth most common cause of cancer-related death. Recent studies have shown that the progression and spread of this type of cancer depends not on the characteristics of the tumour cells themselves, but on their surroundings – the so called tumour microenvironment. This complex network of cells, molecules and tissues surrounds the tumour and has a critical influence on its development and progression. It has been shown that within this environment, the activation of different Toll-like receptors (TLRs) in stem cells has both stimulatory and inhibitory effects on the growth and spread of cancer cells, through both direct and indirect interactions with tumour cells. In order to gain a clearer picture of these interactions, we aim to develop new stem cell lines that will allow reversible and precise activation of TLR signalling pathways in terms of position and timing. Conventional methods for studying receptor signalling are based on genetic manipulation of the receptor concerned or treatment with natural activators. However, these approaches often result in irreversible changes in the cells. We will use the principle of optogenetics to develop cell lines that are more precise in their positioning and timing, as well as more operationally and financially advantageous. This involves attaching a photosensitive protein from yellow-green algae to the receptors in question, which can then be activated by blue light. This will enable the researchers to study the specific effects of the TLR signalling in and on stem cells, on tumour cells, and on various cells in the tumour microenvironment. The goal is to use these knowledge to develop new, targeted approaches for the treatment of colorectal cancer. The basic research project will be carried out in cooperation with Helmut Dolznig from the Medical University of Vienna and Lasse Jensen of Linköping University and is financed by the Austrian Science fund (FWF), Project ID ESP 547-B. Principal Investigator: Anna Stierschneider, PhD Mentors: Dipl.-Ing. Dr. Franz Herzog Prof.(FH) Mag. Dr. Christoph Wiesner