1. Genetic & Structural investigation of Nuclear Receptors Nuclear receptors (NRs) are one of the most diverse and well-reported family of proteins. They are involved in numerous cellular processes as they play pivotal roles in cell signaling and cell cycle. In this project an effort will be made to elucidate the molecular pedigree of this superfamily. A phylogenetic tree will provide evidence on the evolution of nuclear receptors. In house preliminary data indicate that the family of Glucocorticoid receptors (GRs) is the ancestral species of all Nuclear receptors. Estrogen receptors (ERs) seem to have followed GRs in evolution. Supporting this finding is the fact that GRs are stress regulating machines and in the early ages of evolution on this planet, ancestral species would have used them to overcome environmental fluctuations and overall unstable living conditions towards their survival. Going back in time and life complexity at the times when early species had the first ancestral nuclear receptor, it makes more sense to have the necessary molecular machinery to overcome stress factors rather than having Estrogen receptors. 2. Carcinogenic pesticide control via hijacking endosymbiosis Pesticides have little, if any specificity, to the pathogen they target in most cases. Wide spectrum toxic chemicals are being used to remove pests and salvage crops and economies linked to agriculture. The burden on the environment, public health and economy is huge. There are many very widespread pests, whose impact is devastating on a repertoire of crops. To date, there is no specific pesticide nor agent to control them. In this project an effort will be made to develop a novel strategy to manage those pest via deploying a holistic genetic and bioinformatic approach that will control their spread, via inhibiting the key functional and metabolizing enzymes of their endosymbiotic bacterial strains. Our methodology, provides the means to design, test and identify highly specific pest control substances that minimize the impact of toxic chemicals on health, economy and the environment. 3. Antiviral Drug Design: HCV Enzymatic Assay A very fast and cost efficient approach to scan large number of potential inhibitors of the HCV helicase has been developed in our group. In this project an effort will be made to screen for new compounds that will be synthesized via our network of Medicinal Chemistry collaborators and will be send for testing. Data coming out of the assay will eventually feedback the drug design process, thus leading to even more active and potent species of the existing inhibitors. A first version of this rapid assay has been published in Nature Protocol Exchange. 4. Genetic Diseases: Cadasil CADASIL disease belongs to the group of rare diseases. It is well established that the Notch3 protein is primarily responsible for the development of CADASIL syndrome. In this project an effort will be madeto shed light to the actual molecular mechanism underlying CADASIL via insights that we have from preliminary in silico and genetic studies on the Notch3 protein. At the moment, we are aware of a series of Notch3 point mutations that promote CADASIL. In this direction, we investigate the nature, extent, physicochemical and structural significance of the mutant species in an effort to identify the underlying mechanism of Notch3 role and implications in cell signal transduction. Overall, our in silico study has revealed a rather complex molecular mechanism of Notch3 on the structural level; depending of the nature and position of each mutation, a consensus significant loss of beta-sheet structure is observed throughout all in silico modeled mutant/wild type biological systems. 4. Computer-aided Drug Design: flaviviridae inhibitors Based on the x-ray determined structure of HCV helicase, the three dimensional structures of various other helicases that belong to the family of Flavi viruses were established by homology modelling. In this project an effort will be made to design new inhibitors using structure based de novo drug design algorithms. The aim is to eventually design a universal inhibitor compound that will be active in all helicases. Various active compounds in the mM range have already been designed, synthesized and tested for their biological activities. More than 30 publications have been published the last 5 years from our group on this project. Check publications Likewise, the three dimensional structure of the HCV and BVDV polymerases have been solved by x-ray crystallography. Based on those two structures, the three dimensional structures of the Dengue, West Nile, Yellow fever and Japanese Encephalitis Viruses, all members of the family of Flavi viruses will be established by homology modelling.
Undergraduate Teaching: 1. Genetics 2. Modern Genetics (spacial chapters) 3. Genetic Diseases 4. Evolution 5. Bioinformatics To access eClass click here Postgraduate Teaching: 1. Arg. University of Athens: Systems Biology 2. Medical School of Athens: Pharmacogenetics 3. Medical School of Patras: Next Generation Sequencing Dissertations Available (ΔΙΠΛΩΜΑΤΙΚΕΣ) - if interested please contact me