Long-term imaging and spatio-temporal control of living cells using targeted light based on closed-loop feedback.

The ability to optically interact with cells on both an individual and collective level has applications from wound healing to cancer treatment. Building systems that can facilitate both localised light illumination and visualisation of cells can, however, be challenging and costly. This work takes the Dynamic Optical MicroEnvironment (DOME), an existing platform for the closed-loop optical control of microscale agents, and adapts the design to support live-cell imaging. Through modifications made to the imaging and projection systems within the DOME, a significantly higher resolution, alternative imaging channels and the ability to customise light wavelengths are achieved (Bio-DOME). This is accompanied by an interactive calibration procedure that is robust to changes in the hardware configuration and provides fluorescence imaging (Fluoro-DOME). These alterations to the fundamental design allow for long-term use of the DOME in an environment of higher temperature and humidity. Thus, long-term imaging of living cells in a wound, with closed-loop control of real-time frontier illumination via projected light patterns, is facilitated. Supplementary Information: The online version contains supplementary material available at 10.1007/s12213-024-00165-0.

Comparative assessment of genes driving cancer and somatic evolution in non-cancer tissues: an update of the Network of Cancer Genes (NCG) resource.

BACKGROUND: Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development. RESULTS: Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues. Mapping the alterations of these genes in 7953 pan-cancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and non-cancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation. CONCLUSIONS: Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and non-cancer somatic drivers, their literature support, and properties are accessible in the Network of Cancer Genes and Healthy Drivers resource at http://www.network-cancer-genes.org/ .

Normal Somatic Mutations in Cancer Transformation.

Gene alterations play a prominent role in driving cancer initiation and progression. However, the genetic events that occur in normal cells prior to tumorigenesis are still unknown. Recent studies have started to map somatic mutations in normal human tissues, and here we discuss their implications for our understanding of tumorigenesis.