Nanobiology of Cancer

Modelling Biomolecular Signalling Pathways in Colorectal Cancer Cells by Using Multidimensional Correlative Imaging Techniques
In this project we endeavour to further elucidate the complex and dynamic machinery of membrane transport and signalling mechanisms that have been shown to be a key event in colorectal tumour cell survival and further metastatic outgrowth. In this project we will apply cutting-edge 3-D and 4-D microscopic methods in combination with correlative immunocytochemistry- and molecular biology techniques to address the aims of the study.
Investigators: ;

X-Ray Micro-Computed Imaging of Bioreactor Liver Tissue: A Model for Colorectal Metastasis
In previous studies we successfully imaged liver tissue and its associated vasculature via soft X-ray micro-computed imaging. In this research project we aim to image, reconstruct and model colorectal cancer growth in a liver organoid bioreactor via X-ray micro-computed tomography. This approach will be an unique set-up in the study and screening of potential anti-cancer drugs.

3-D Microscopic Analysis of Colorectal Cancer
This fundamental research project addresses problems of collecting currently unknown architectural tissue and (sub)cellular information by reconstructing and modelling colorectal liver metastasis pathways using novel correlative tomographic imaging methods. Identifying the mechanisms regu-lating the nanobiology of colorectal liver metastasis, as well as gaining a better understanding of the interaction between the metastatic tumour cell and the different types of liver cells, including the liver vasculature, will provide a foundation for new therapeutic approaches. The correlative data and models achieved will be a breakthrough in the study of liver tumours.

Apoptosis-inducing Anti-Actin Drugs: A Potential Approach for Suppressing the Onset of Hepatic Metastasis
Mounting literature evidence reveals that alterations of actin polymerization plays a pivotal role in regulating the metastatic behaviour of a malignant cell. In line, we found in a preliminary study by using actin-binding agents a relationship between actin-mediated fine structural changes and an in-crease in the number of apoptotic colorectal cancer cells. The identification of anti-actin drugs which exerts severe cytotoxic cellular effects by inducing apoptosis in colon carcinoma cancer cells are relatively unexplored and form the basis of this research project. This should in the long-term con-tribute to the development of new chemotherapeutic strategies.

Development of Correlative Fluorescence- and Scanning, Transmission Electron Microscopy Imaging Methods for Biomolecular Investigation of Colorectal Metastasis
In this project we aim to develop novel imaging analysis techniques to detect and image the specific localisation of small biomolecules within subcellular structures of the same cancer cell(s) using ad-vanced immunogold techniques such as nano and decagold technology in conjunction with correlative confocal, X-ray and electron microscopy.

Transendothelial Transport Mechanisms of the Hepatic Sinusoid: From Cell to Molecule
The liver sinusoidal endothelium plays a central and active role in regulating the exchange of mac-romolecules, solutes, fluid and (cancer) cells between the blood and the surrounding tissues. The high permeability of the liver sinusoidal endothelium to these substances are reflected in the presence of special transporting systems represented by non-diaphragmed fenestrae, coated pits, caveolae, vesicle vacuolar organelles and receptor-mediated scavenger mechanisms. This ongoing research project endeavours to elucidate further the complex and dynamic machinery of liver transendothelial transport mechanisms by applying high-resolution 3-D and 4-D correlative microscopic methods