Sysmic

All processes of life occur in space and time, but present experimental methods for systems biology have limited ability to resolve this spatiotemporal complexity. Indeed, systems biology has typically aggregated these dimensions in population-based studies of cellular processes.

Therefore, there is a need to develop and use methods to collect data and build models for single living cells in four dimensions; three-dimensional space and time. To this end, the coordinator recently initiated and coordinated the development of the Systems microscopy strategy within the frame of an EU-supported Network of Excellence (NoE).

The use of this key enabling technology platform, from living cell to algorithm, will be a cornerstone for next-generation systems biology to elucidate and understand complex and dynamic molecular, sub-cellular and cellular networks. The current program builds on the advances in Systems microscopy made within the successful European NoE and utilize these to better understand cancer cell migration.

The core biological theme of this program is cell migration; a basic but complex cellular process that is highly relevant to human cancer. This complexity is, in part, explained by plasticity in the possible cell migration strategies that cells adopt and by the fine-tuned spatiotemporal coordination of migratory forces. However, the molecular mechanisms and genetic regulation that give rise to cell migration plasticity and dynamic force control constitutes knowledge gaps that this program aim to fill.

We will here further develop and apply the systems microscopy strategy by combining the recently developed quantitative imaging and statistical modeling with developing

(i) integrin tension sensors,

(ii) correlative traction force microscopy,

(iii) single cell proteomics, and

(iv) multiplex in situ protein detection.

We will also combine in a novel manner dynamic microscopy observations of migrating cells with RNA-seq and proteomics. All this is tailored to add to the understanding of cellular dynamics during cell migration. Finally, we will explore developed migration and traction force models and profiling methods on 25 different cancer cell lines.

We expect to commercialize novel technology through the participating companies Olink Bioscience and Sprint Bioscience. We also expect to unravel novel molecular mechanisms controlling cell migration, thereby identifying potential therapeutic targets in cancer, inflammation, and other cell migration-dependent pathologies and to seek further industry partnerships for the exploration of these targets.

To achieve this, this program brings together leading experts in advanced light microscopy and cell adhesion and migration (Staffan Strömblad, Karolinska Institute; Pontus Nordenfelt, Lund University); molecular imaging technologies (Ulf Landegren, Uppsala University); image analysis (Carolina Wählby, Uppsala University); genomics, bioinformatics and modelling (Carsten Daub, Karolinska Institute); and systems biology (Daub; Strömblad); as well as the industry partners (participating pro bono) with strong experience in imaging technology development and commercialization (Matthias Howell, Olink Bioscience) and in medicinal drug development (Anders Åberg, Sprint Bioscience).