Projects / Programmes
Ecotoxicology, toxicogenomics and carcinogenesis
January 1, 2015
- December 31, 2018
| Code |
Science |
Field |
Subfield |
| 1.08.00 |
Natural sciences and mathematics |
Control and care of the environment |
|
| 1.03.00 |
Natural sciences and mathematics |
Biology |
|
| Code |
Science |
Field |
| T270 |
Technological sciences |
Environmental technology, pollution control |
| Code |
Science |
Field |
| 1.05 |
Natural Sciences |
Earth and related Environmental sciences |
WP1: Algae, Ecotechnology, Cyanobacteria blooms, Ecological status, Phycocyanin, Phytoplankton, Stress;
WP2: Genotoxicity, Environmental pollutants, Complex mixtures;
WP3: Apatmers, Cancer stem cells, Circulating tumour cells, Exosomes, Glioma, Mesenchymal Stem Cells, Tumour biomarkers.
Researchers (22)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0105 |
National Institute of Biology |
Ljubljana |
5055784 |
0 |
Abstract
ECOTOXICOLOGY, TOXICOGENOMICS AND CARCINOGENESIS: CELLULAR AND MOLECULAR MECHANISMS
In the developed countries one in four deaths results from cancer. The increasing incidence of cancer partially results from environmental pollution. This Program aims to extrapolate global climate changes related to aquatic ecosystems, being increasingly polluted by natural and synthetic toxins, to the effects on diseased environment and humans, via a plethora of possible interactions at organism, cellular and molecular levels.
The Programme comprises of two scientific aspects – the first is the observational, analysing global changes indicators, such as decline in biodiversity of harmful cyanobacterial blooms in eutrophic surface waters, requiring the redefinition of bioindication, based on standard specific biological elements. The spatio-temporal component is also becoming more relevant in the evaluation of ecological status and environmental protection strategies. Our mission is to provide novel concepts in waters status, where we are suggesting new monitoring modalities, using morphological and bioinformatics approaches, and offering innovative bio indicators and related eco-technologies, like computer controlled robotised probes for water ecological status monitoring. This knowledge is shared with the industry and transferred nationally in monitoring programmes and internationally.
Early warnings on the dangerous effects of natural and synthetic toxins on higher organisms, resulting from our mechanistic studies, present the second aspect of this Programme, focusing on prevention and possible treatment of diseased states of the environment and human. This involves the studies of anthropogenic substances, i.e. the effects of spilling drugs’ remnants in the water environment, use of nanotechnology products and yet unknown effects of food additives on humans, where novel systems biology approaches and animal testing in zebra fish models are required. Food technologies are increasingly controlled and demand relevant investigations, including new biotechnologies (e.g. algal products), as proposed in this Programme.
All above lead to better prevention of disease, in particular cancer, e.g. glioma. We will analyse the impact of less known environmental factors from, e.g. modern communication technologies on cancer initiation, progression and resistance to therapies, mostly regarding the presence of variable amounts of cancer stem cells. We propose to reveal novel biomarkers of these cells with substantial bioinformatics support and to introduce novel aptamer technologies for following these cells and their products in (non-invasive) biopsies. In the studies on tumour microenvironment, in vitro cellular and in vivo animal models will be used for drug testing in collaboration with pharmaceutical industry. Together with those, novel approaches using electroporation for optimizing cellular vectors transfer, proposed for glioma treatment, will lead to clinical translation.
Significance for science
The speed of global climate change is becoming a painful reality, effecting also aquatic ecosystems, as the adaptation of individual species varies. The most efficient adaptation is achieved via selection, where organisms with high reproduction rates are privileged. As the result, we can expect decline in biodiversity. This affects the self-renewal ability of ecosystems, having a log term reciprocal effects on the global climate. There are many indicators that global changes could be the cause of higher toxicity of harmful cyanobacterial blooms in eutrophic surface waters. Basic research in the bloom dynamics, related to environmental changes’ indicators, which is resulting from our improved original measurements design, as we are proposing here, might revolutionise the field.
This concept is the key scientific premise of this Programme, which also relates to anthropogenic pollution. Creative scientific solutions and innovative approaches in their application are the only tool by which we can contribute to the prevention of the effects from emerging environmental pollutants.
The toxicogenomic research proposed here will provide the missing data, new knowledge on the molecular mechanisms of the effects of individual compounds and complex mixtures of environmental pollutants and new data analysis protocols for predicting their long term potential and delayed effects on life forms upon the exposure to low doses. The application of the proposed combination of traditional toxicological tests with the latest “omics” technologies and bioinformatics will enable identification of molecular biomarkers of the mechanisms of action that are in line with the biological complexity of the underlying processes. In the field of experimental as well as science based regulatory toxicology this is important, as there is an urgent need to develop new strategies and methods to screen and evaluate large numbers of chemicals for potential adverse effects. The resulting information will enable prioritisation of most efficient entities and endpoints to define the risk to health.
Carcinogenesis, which results from the imbalances described above, has moved the focus into understanding of cellular origin of cancer, where our research on the dual role of - cancer and normal - stem cells, present in the tumour, is increasingly relevant. We propose to investigate these cells and their interactions, mostly from the aspect of their biomarkers, possibly also therapy targets, urgently needed in oncology. These will be tested in novel alternative fish models, more efficiently translating their application to clinical trials. Specific scientific challenge is to find new principles related to the stem cells as therapeutics, as well as cancers stem cells, as (their) therapy targets. Here, we will apply new methodology, the oligonucleotide aptamers, overcoming the problems of antibodies application in clinical oncology.
Significance for the country
The Programme is addressing highly relevant issues of Slovenia societal problems, e.g. environment and health, as increasing environmental pollution is increasing the incidence of diseases such as cancer, both issues being also highlighted in EU Horizon 2020 research and innovation strategy. For example, we need waters with "good ecological status" in accordance with the EU Water Framework Directive. Primary producers e.g. cyanobacteria and algae, the subjects of our research are indicators of water quality and key elements for its biological assessment. Frequent blooms of cyanobacteria clearly indicate a disturbed dynamics of ecological balance. In toxicology, complex systems biology approaches will lead to assessment of health risks of exposure to multiple toxic substances. The proposed studies on naturally and anthropogenically induced pollution also aim to increase the awareness of public and policy makers, associated with environment and health risks regulations, resulting in national guidelines and directives for coordinated risk assessment.
These are very important also for prevention of cancer, where better understanding of cancer initiation at the cellular and molecular level will result in novel relevant biomarkers. In predictive medicine and clinical oncology, a plethora of novel biomarkers shall offer a more personalised patients’ treatment. The validation of biomarkers in animals is crucial translation step, where the trends move to use of alternative animal models to the costly higher organisms’ trials. The proposed development of zebra fish model enables high throughput at lower cost both in toxicology and the preclinical evaluation of biomarkers as novel therapy targets. The latter not only contributes to improve general health, but also lowers the cost of ”unnecessary” therapies, improving health system economy.
In EU as well is Slovenia, economic challenges are approached by the efforts to enhance transition of knowledge from research to production. This Programme is offering ecotechnologies, such as new robotised vessel for cyanobacteria blooms control. We are also proposing novel approaches in algal biotechnology products. Translating cancer research into clinics, as planned here, is associated with new opportunities for biomedical and pharmaceutical industry in Slovenia and thus contribution to economic growth. Further, we already collaborate with the Centre of Excellence COBIC in designing aptamers’ biomarkers and products for selecting cells and small molecules to be used for diagnostic and therapeutic purposes. Cellular models for testing, and the stem cell research offer numerous possibilities for application and collaboration with regenerative medicine related companies.
The Programme also comprises the dissemination of knowledge to students, and researchers’ training, an important investment for economical development of the country.
Most important scientific results
Annual report
2015,
2016,
2017,
final report
Most important socioeconomically and culturally relevant results
Annual report
2015,
2016,
2017,
final report
