European projects

Abstract

A tumour cell uses both genetic and protein weapons in its development. Gaining a greater understanding of these lethal mechanisms is a key step towards developing novel and more effective treatments. Because the metal ion metabolism of a tumour cell is not fully understood, we will address the challenge of explaining the mechanisms of how a tumour cell copes both with essential metal ions and platinum based drugs. The metal-based mechanisms help a tumour to grow on one side and to protect itself against commonly used metal-based drugs. On the other side, the exact description of these mechanisms, which are being associated with multi-drug resistance occurrence and failure of a treatment, still remains unclear. We will reveal the mechanism of the as yet not understood biochemical and molecularly-biological relationships and correlations between metal ions and proteins in a tumour development revealing the way how to suppress the growth and development of a tumour and to markedly enhance the effectiveness of a treatment.

To achieve this goal, we will focus on metallothionein and its interactions with essential metals and metal-containing anticancer drugs (cisplatin, carboplatin, and oxaliplatin). Their actions will be monitored both in vitro and in vivo. For this purpose, we will optimize electrochemical, mass spectrometric and immune-based methods. Based on processing of data obtained, new carcinogenetic pathways will be sought on cell level and proved by genetic modifications of target genes. The discovered processes and the pathways found will then be tested on two animal experimental models mice bearing breast tumours (MCF-7 and 4T1) and MeLiM minipigs bearing melanomas.

The precise description of the tumour related pathways coping with metal ions based on metallothioneins will direct new highly effective treatment strategies. Moreover, the discovery of new carcinogenetic pathways will open a window for understanding of cancer formation and development.

Abstract:

Increasing chemical pollution seriously compromises the health of ecosystems and humans worldwide. Hazardous compounds, such as polycyclic aromatic hydrocarbons, heavy metals and emerging pollutants contaminate soils/sediments, ground and surface waters. To prevent/minimise the risks associated with the accumulations of these chemicals in the environment it is key to establish low-cost/green methodologies for the treatment and redevelopment of contaminated areas. Several physico-chemical methods have been explored to remove pollutants in the environment, but these are complex, energy consuming or expensive. The exploitation of the capability of bacteria, fungi and phototrophs to transform toxic contaminants into harmless end-products, can lead instead to cheap and sustainable bioremediation alternatives.

GREENER proposes the development of innovative, efficient and low-cost hybrid solutions that integrate bioremediation technologies with bio-electrochemical systems (BES). BES, such as microbial fuel cells, break down organic contaminants through the action of electroactive bacteria while generating electrical current. We will investigate the synergetic effect of different bioremediation strategies and demonstrate effective pollutants removal in water and soil/sediments, while generating side products of interest, such as bioelectricity. The type and entity of contamination, along with the specific physico-chemical/microbial characteristics of the environment to be depolluted, will feed into a decision-making toolbox. The latter will allow the establishment of ad hoc integrated solutions, which will take into account effectiveness of biodegradation, costs, environmental risks and social aspects. Fundamental research will be performed at lab-scale, while pilot-tests will be used to proof the scaling-up feasibility for field applications. Environmental benefits and risks, compared to standard remediation approaches, including energy efficiency, will be investigated.