Optogenetic stem cells in heterotypic tumor spheroids

A new project headed by Anna Stierschneider, a senior postdoctoral researcher at the IMC Krems University of Applied Sciences, is designed to generate significant new insights into the development and progression of colorectal cancer tumours and, in turn, to promote the development of innovative therapies. At its most recent meeting, the Board of the Austrian Science Fund (FWF) approved 21 out of a total of 67 applications for the ESPRIT postdoctoral programme. The aim of the Early-Stage Programme: Research, Innovation, Training (ESPRIT) programme is to promote the careers of highly qualified postdoctoral researchers from all disciplines. Focused on medical biotechnology, this FWF-funded basic research project is being implemented in cooperation with Helmut Dolznig from the Medical University of Vienna and Lasse Jensen of Linköping University. Anna Stierschneider will receive support from her mentors, Franz Herzog and Christoph Wiesner of IMC Krems. With around 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 deaths. Recent studies have shown that the progression and spread of this type of cancer does not depend on the characteristics of the tumour cells themselves, but on their surroundings known as the tumour microenvironment. This complex network of cells, molecules and tissues surrounds the tumour and has a decisive 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, by means of both direct and indirect interaction with tumour cells. In order to gain a clearer picture of these interactions, the research group at IMC Krems aims to develop new stem cell lines that will enable reversible and precise activation of TLR signalling pathways in terms of position and timing. Conventional methods for examining receptor signal pathways are based on genetic manipulation of the receptor concerned or treatment with natural activators. However, these approaches frequently result in irreversible changes in the cells. Anna Stierschneider will use the principle of optogenetics to develop cell lines that are more precise in their positioning and timing, and also 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. As a result, the researchers will be able to examine 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 findings as the basis for developing new, targeted approaches for the treatment of colorectal cancer.