NovaMechanics awarded funding for the following projects:
The NanoMILE project intends to establish a fundamental understanding of the mechanisms of nanomaterial interactions with living systems and the environment, across the entire life cycle of nanomaterials and in a wide range of target species. The project will identify critical properties (physico-chemical descriptors) that confer the ability to induce harm in biological systems. This is key to allowing these features to be considered in nanomaterial production (“safety by design”).The overarching objective of NanoMILE is thus to formulate an intelligent and powerful paradigm for the mode(s) of interaction between manufactured Nanomaterials (MNMs) and organisms or the environment to allow the development of a single framework for the classification of nanomaterial safety and the creation of a universally applicable framework for nanosafety.A wide range of manufactured MNMs will be sourced and characterized throughout their life cycle. Using a high throughput screening process, a streamlined testing and selection platform will be developed and applied to refine the MNMs selection. The selected MNMs will undergo focused testing relative to their mechanism(s) of effects on living systems and the environment. An iterative experimental / modeling process will integrate the data obtained into quantitative structure or properties / effects relationships.
- nanoMILE: Enginneered nanomaterial mechanisms of interactions with living systems and the environment: a universal framework for safe nanotechnology FP7 funded project (2013-2017) (link)
THALAMOSS (THALAssaemia MOdular Stratification System for personalized therapy of beta-thalassemia) is aimed at development of universal sets of markers and techniques for stratification of β-thalassaemia patients into treatment subgroups for (a) onset and frequency of blood transfusions, (b) choice of iron chelation, (c) induction of fetal hemoglobin, (d) prospective efficacy of gene-therapy. At present, no framework exists to guide therapeutic decisions and personalised treatment of β-thalassaemia.
- THALAMOSS: THALAssaemia MOdular Stratification System for personalized therapy of beta-thalassemia FP7 funded project (2012-2016) (link)
This COST Action aims to unite researchers with expertise in rational drug design and the medicinal chemistry of synthetic and natural compounds with biomedical investigators dedicated to the understanding the mechanisms governing drug resistance in cancer stem cells. Cancer stem cells (CSC) are a subpopulation of cells within tumors that exhibit enhanced tumor-initiating attributes and are a major contributing factor to current cancer therapy failure. The CSC phenotypic state comprises distinct molecular and functional differences that underpin resistance to current treatments and the unique ability spread and to seed new tumors throughout the body. This insight necessitates an entirely new approach to cancer drug development to effectively target tumor CSCs. Through exchange of information, experience and expertise, researcher mobility and fostering new collaboration between chemistry and biology groups, the Action endeavours to develop new, effective methods for identifying novel compounds and drug candidates that target drug-resistant cancer stem cells.
- "Chemoinformatic solutions for the identification and optimization of agents for the treatment of thalassaemia" (2011-2013)
The main aim of this project is to discover agents which have higher efficacy and are safer than existing drugs through the development of a novel pathway for drug discovery and design involving the use of molecular modeling and data mining. Data generated by biological screening process will be used to develop a predictive combinatorial QSAR model that will define a set of structural criteria required for HbF inducing activity without the need for identifying a specific target molecule. Molecular modeling will be employed to design/identify a small number of compounds which will be expected to have higher HbF inducing activity and reduced cytotoxicity than the original analogues.
The contribution of NOVAMECHANICS will be the development of advanced mathematical models for predicting environmental durability and ageing resistance with respect to environmental factors (temperature, humidity, etc.) and material structure. A computational procedure will be developed to identify the most critical among the influence parameters for the models. Furthermore, the accuracy and prediction ability of the produced mathematical models will be validated by measuring the correlation between the model predictions and “real life” results. Material ageing Versus Time curves will also be developed. The models will be used to design new high-quality products with minimum investment in time and money for experimental work. Based on the experimental results an addendum to ISO 21207 (International Standards Organisation) will be suggested. This addendum will describe the accelerated test methods in the format of a formal addendum to the existing International Standard. In collaboration with National Standards Bodies and the other participants, a proposal will be made to ISO and to its relevant Technical Committee ISO/TC 156 for adoption as the new and enriched version of ISO 21207.
PATHOSYS focuses on the development of novel and generally applicable mathematical methods and algorithms for systems biology. These methods and algorithms will be applied to study the complex interactions of hepatitis C virus (HCV), a human-pathogenic virus of high medical relevance, with its host at the systems level. Using a multidisciplinary, integrative approach, PATHOSYS will (a) develop methods to analyze and integrate a wide variety of data from wet lab experiments, databases and biological literature, (b) develop and apply machine learning tools to reconstruct and study intracellular interaction networks from experimental data, (c) develop new and improve existing algorithms and mathematical methods for bottom-up modelling, to fit models to data, and to analyze the dynamic behaviour of models (d) generate new experimental data to gain novel insights into hepatitis C virus host interactions, and (e) use the newly developed methods and data to model and analyze HCV-host interactions at the systems level.
- "New Algorithms for Host Pathogen Systems Biology" (PATHOSYS) FP7 funded project (2010-2014) (link)
Guided by biological data, PATHOSYS focuses on the design of novel algorithms and mathematical methods for systems biology, with the aim to provide generally applicable tools to elucidate biological processes. Based on developed models and using systems analysis, PATHOSYS will elucidate virus host interactions of Hepatitis C virus at an unprecedented level. As a direct spin-off, models and analysis methods developed in PATHOSYS will lead to the identification of new candidate host cell target genes applicable for the design of novel anti-viral drugs against hepatitis C. Targeting of host cell factors will reduce the likelihood for the development of therapy resistance and increase the chance for broad-spectrum anti-virals. Inclusion of two SME partners will ensure exploitation of results generated in PATHOSYS and their transfer into industrial and pharmaceutical applications, thus strengthening economy and health care system in Europe.
The aim of this project is the development of alternative in silico models for the evaluation of toxicity of chemicals and a prioritized list of compounds for experimental in vivo testing. Recent (Q)SAR developments allow much more accurate prediction of complex toxicological endpoints than a few years ago. This progress is due to (i) the development of improved (Q)SAR methodologies and (ii) by the availability of larger and better curated public databases. The QSAR models that will be developed for predicting the in vivo adverse health effects of compounds will use both biological and chemical descriptors. The ultimate goal of this project is to construct a prioritized list of compounds with low potential for in vivo toxicity. This list of compounds will be proposed for experimental testing and will be of particular interest for the REACH and other similar projects.
- “Development of Robust Computational Models of Chemical Toxicity for Health and Environmental Risk Assessment” (2009-2011) Project Website (link)
The aim of the project was the rational drug design, with the development of in silico modeling methods, synthesis and biological evaluation of new active Rheumatoid Arthritis small molecules. The developed method, due to the high predictive ability and simplicity, could be a useful aid to the costly and time-consuming experiments for determining the TNF-a inhibition. The method can also be used to screen existing databases or virtual combinations to identify derivatives with desired activity. The developed in silico workflows to help researchers to design novel chemistry driven molecules with desired biological activity.
- “In Silico Modelling, Prediction, Synthesis and Biological Evaluation of Novel Rheumatoid Arthritis Inhibitors” (2009-2011) Project Website (link)
In this project we have developed an in silico model to predict the inhibition of β-amyloid aggregation by small organic molecules. In particular we have explored the inhibitory activity of a series of small molecules acids using Kohonen maps and Counterpropagation Artificial Neural Networks. The effects of various structural modifications on biological activity are investigated and novel structures are designed using the developed in silico model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds was described.
- “Benzo[1,2,4]triazinones: Inhibitors of β-Amyloid Aggregation - New Leads for the Fight Against Alzheimer's Disease” (2008-2010)
Excessive or insufficient angiogenesis (new blood vessel formation) is connected with many human diseases, cancer included. For effective disease intervention, interdisciplinary approach in the research is necessary. This COST Action focuses on networking of interdisciplinary oriented chemistry and biology researchers who are actively involved in rationale designing and development of small organic compounds with anti-angiogenic properties. Exchanges of information and presentations of experiences and skills from chemical and biological research will be performed for effective introduction, exploitation and improvement of modern methods for development of new angiogenic inhibitors. Meetings, short-term scientific missions, workshops, training schools and conference will ensure the expansion of effective cooperation in the development of new drug candidates.
- "Inhibitors of angiogenesis: design, synthesis and biological exploitation" (ANGIOKEM) CMST Action COST CM060 (2007-2011) Project Website (link)
Acknowledgements: The projetcs are co-funded by Republic of Cyprus, Cyprus Research Promotion Foundation, European Regional Development Fund (ERDF) and European Union.