Work was carried out in 6 work packages (WPs). WP1 identified how a panel of clinically relevant cancer-associated mutations reprogram cellular communication in breast epithelium. This comprised preparing a working model - introducing biosensors to prototype cancer models, setting up image acquisition, image quantification and data analysis pipelines, and acquiring the data. This allowed to identify mutation-specific pathological cellular signalling patterns. We found that a large part of this network is based on cell-cell communication across the tissue. This demonstrates that in tested cancer models oncogenic signalling is a tissue-scale property. This yielded data for 3 conference presentations including EACR Congress –the major cancer research conference in Europe.
WP2 aimed to identify how mutation-reprogrammed epithelium responds to standard drug treatments. We found that mutation-reprogrammed epithelial tissue capitalizes on fundamental epithelial homeostasis mechanisms to grow uncontrollably and resist targeted therapy. These findings so far resulted in 4 conference presentations, 3 of which were selected for conference talks. In addition, part of the work carried in WP2 contributed to peer-reviewed journal publication (Mol Syst Biol) and yielded datasets for the development of image quantification/analysis methods.
WP3 explored oncogenic mutation-reprogrammed tissue properties in three-dimensional in vitro models. This involved studies using the reductionist MCF10A mammary morphogenesis model and patient-derived organoids. The studies on the MCF10A spheroid model demonstrated that increased cell-cell communication allows cancer cells to escape programmed cell death and distorts mammary gland architecture, allowing uncontrolled growth. The planned work on PDOs was substituted with work on genetically modified mouse organoids (due to a lack of suitable PDOs from the biobank) and is still ongoing through external collaboration. The results of this part of the study so far contributed to 1 peer-reviewed journal publication (Dev Cell), and 1 publication in preparation that will combine the major findings of WP1, WP2, and WP3.
In WP4 the fellow received extensive technical training through the implementation of NOSCAR in the host laboratory – a laboratory with strong expertise in spatiotemporal bioimaging and quantitative image analysis. The fellow gained expertise in advanced imaging, computer vision-based image quantification, biosensor technology, and analysis of large datasets using computational and statistical methods. In addition, the fellow gained knowledge in breast cancer and received advanced training in applications of organoid technologies and techniques for mammary gland research at EMBL.
The WP5 focused on transferable skills for career development. The fellow completed COMET - Coaching, Mentoring, and Training – University of Bern’s Career Programme and received leadership, project management, and fund acquisition training. In addition, she co-supervised junior researchers (1 master's student, 1 bachelor's student, and 1 doctoral student), and was involved in grant writing. Beyond providing new skills, the training activities of WP4 and WP5 greatly added to the growth of fellow’s professional network.
In WP6 the fellow disseminated and communicated the research to the public, and scientific community. The fellow took an active part in popularising science through science outreach events “Science is Wonderful!” and “Research Night” at the University of Bern. She presented her research at 8 international conferences and workshops and coauthored 2 research articles.
