Author Archives: admin

Tuesday 23 July 2019 16:00 – 17:00 Seminar Room 1

“Numerical methods and development of Imaging techniques for Structural Health Monitoring applications”

Dr. Christos Panagiotopoulos Institute of Applied and Computational Mathematics (IACM)

Abstract
Research and development issues on material related to Structural Health Monitoring (SHM) worked during the ARCHERS project will be presented through a variety of related topics. First, an Operational Modal Analysis currently developed framework based on Stretching Method is examined and further applied to the case of the old Egyptian lighthouse of Rethymno. Using signal processing results within the Stretching Method framework we set up a minimization problem in order to appropriately define a simple mathematical model of the structure amenable for further numerical processes. Second, Time Reversal for Structural Analysis of frame structures will be covered in order to show whether it fits well as a numerical tool for source and damage localization problems. Another important issue of SHM is the Acoustic Emission that is the phenomenon of radiation of acoustic (elastic) waves in solids that occurs when a material undergoes irreversible changes in its internal structure. A mixed finite element method capable to simulate such problems of elastodynamics has been developed and will be discussed. Finally, Interface Crack Initiation and Growth in Composite Materials is viewed from the viewpoint of a coupled stress-energy failure criterion, and solved as a minimization problem developing appropriate algorithms and utilizing numerical methods such is the Boundary or the Finite Element Methods. Background theory, implementation of algorithms and applications considered will be discussed, while other subsidiary material occurred from the overall research activity will be briefly presented.

Tuesday 16 July 2019 16:00 – 17:00 A. Payatakes Seminar Room

” The role of Setdb1 in intestinal progenitor cells and in colorectal tumorigenesis”

Dr. Ioanna Peraki Institute of Molecular Biology and Biotechnology (IMBB)

Abstract
Setdb1 is a histone-3-lysine-9 methylase, which is highly expressed in embryonic-stem (ES) cells and in a variety of tumors including breast, skin, liver, colon and lung cancer. Setdb1 enzymatic activity contributes to the generation of a condensed, closed chromatin state and transcriptional repression. Previous studies have demonstrated that Setdb1 in ES cells is required for the suppression of a subset of genes encoding developmental regulators. In this way Setdb1 prevents uncontrolled differentiation, contributing to the mechanisms responsible for the maintenance of the pluripotent, stem cell phenotype. Setdb1 function in cancer is less well explored. While in many cases a correlation between Setdb1 expression and cancer phenotype is well established, evidence for a causative relationship is still missing. The current proposal is based on the hypothesis that similar to ES cells, Setdb1 may also repress differentiation specific regulators in adult somatic stem cells, like the intestinal Lgr5+ progenitor cells. The established role of Wnt signaling in both, intestinal progenitor cell maintenance and colorectal cancer, and the putative oncogenic function of Setdb1 in different organs, warrants parallel studies on the role of Setdb1 in progenitor cell maintenance and in colorectal cancer formation. We thus put forward the hypothesis that Setdb1deficiency may induce premature differentiation of Lgr5+ cells and derivative cancer stem cells, which may influence epithelium renewal or the growth characteristics of intestinal tumors.
To address these questions, we will conduct a study, which combines analyses of relevant mouse models with investigations of intestinal progenitor-derived organoid cultures. We expect this effort will not only decipher the role of Setdb1 in colorectal cancer but may also provide broader insights into the epigenetic mechanisms involved in the maintenanc

Tuesday 9 July 2019 16:00 – 17:00 A. Payatakes Seminar Room

“A generalization of Young measures for the Hydrodynamic limit of condensing Zero Range Processes”

Dr. Marios Stamatakis Institute of Applied and Computational Mathematics (IACM)

Abstract
Zero range processes (ZRPs) are stochastic interacting particle systems with zero range interaction. For particular choices of their parameters they exhibit phase separation with the emergence of a condensate. Such ZRPs are referred to as condensing and their hydrodynamic limit is not known, but is expected to be a degenerate non-linear diffusion equation where the diffusivity vanishes above a critical density ρc. In this talk we propose a generalization of the notion of Young-measures which allows to obtain a closed equation as the hydrodynamic limit of condensing ZRPs. We focus on symmetric ZRPs in the discrete torus and prove that the laws of the empirical density of the ZRP in terms of generalized Young-measures are concentrated on generalized Young measure-valued weak solutions π = (πt)t ≥ 0 to the equation θtπ = ΔΦ(π) where Φ(λ) is the mean jump rate of particles under an equilibrium state of mean density λ ≥ 0. Via the barycentric projection of Young measures and partial progress on the replacement lemma we can pass from the description in terms of generalized Young measures to ordinary measures and thus obtain that in the hydrodynamic limit the fluid phase ρ and the condensed phase ρ┴ οf the ZRP satisfy the equation θtρ – ΔΦ (ρ) = – θt ρ┴. Consequently, the fluid phase evolves according to a non-linear diffusion equation with a source term equal to the negative time derivative of the condensed phase.

Tuesday 25 June 2019 16:00 – 17:00 A. Payatakes Seminar Room

” The Plasmodium NF-Y like complex is required for malaria parasite transmission ”

Dr. Chiara Curra Institute of Molecular Biology and Biotechnology (IMBB)

Abstract

Malaria is transmitted by Plasmodium parasites and has a tremendous impact in the world. The sporozoites, transmitted from the mosquito to the vertebrate host during a mosquito bite, are produced in the mosquito inside the oocyst in about 12 days after blood meal uptake. Oocyst rupture is an essential step for the release of the sporozoites, which next travel to the salivary glands where they will be transmitted to the new host. Here, parasites first invade the liver cells and after they reach the blood stream infecting erythrocytes. Little is known about the mechanism of oocyst rupture and liver cells invasion. Recently, three Oocyst Rupture Proteins (ORP1-3) have been identified with a function in sporozoite transmission. Mutants lacking orps are blocked at oocyst stage, and sporozoites mechanically released are not able to establish infection in the vertebrate host. ORP1 and ORP2 play a role in the mechanism of oocyst rupture through the interaction of their histone-fold domains, similar to subunit B and C of the transcription factor NFY. Also ORP3 has a function during oocyst rupture but the mechanism is not known. ORPs represent a new discovery on how the parasite exploits protein domains to provide vital functions such as oocyst rupture and liver cells invasion. ORPs, or their specific domains, could be a possible target for anti-malarial strategies development to stop malaria transmission to the vertebrate host.

Tuesday 18 June 2019 16:00 – 17:00 A. Payatakes Seminar Room

” Liposomes and cellular vesicles: Νovel applications for effective drug targeting”

Dr. Antonia Marazioti Institute of Chemical Engineering Sciences (ICE-HT)

Abstract
Liposomes are well known for their potential applications as efficient carriers for drug delivery, with the most common administration route so far being intravenous administration. Little is known about the potential therapeutic advantages as well as the retention of topically administered liposomal drugs into confined body cavities. In the present study the retention of various types of liposomes in the pleural cavity of healthy mice and mice with malignant pleural effusion (MPE) following their intrapleural administration was monitored by live animal imaging. The experimental results reveal that certain liposome preparative parameters, such as the liposome size/lamellarity and coating with PEG-lipids, significantly affect the local bioavailability of liposomes. Furthermore, no difference was noticed in liposomal retention between tumorinoculated (MPE) and healthy mice, indicating the stability of liposomes in the presence of effusion. Interestingly, when we administered intrapleurally a liposomal formulation of deltarasin, to an experimental mouse model of MPE, fluid accumulation was halted, indicating the high potential of this route of administration as a method to increase the therapeutic potential of liposomal drugs for local diseases. In parallel, we studied the exosome inspired cell derived vesicles (CVs) as alternatives to artificial liposomes for targeted drug delivery. We isolated CVs from different cell lines and characterized their properties, morphology, cytotoxicity, integrity, cellular uptake as well as their brain-targeting potential, in vitro and in vivo. Our results provide new insights in the CVs physiology and potential for effective and targeted drug delivery.

Tuesday 16 April 2019 16:00 – 17:00 A. Payatakes Seminar Room

“Autophagy affects neuronal function via cAMP signalling”

Dr. Thanos Metaxakis Institute of Molecular Biology and Biotechnology (IMBB)

Abstract
Neuronal autophagy is an evolutionarily conserved catabolic process that facilitates recycling of dysfunctional cellular constituents and survival of nerve cells under adverse nutritional conditions. Importance of intact autophagy on neuronal homeostasis preservation is explicitly proven by the severe consequences of its blockage on neuronal survival and functionality: loss of neuronal autophagy causes neuronal pathologies, including neurodegeneration and stroke, while promoting age-related neuronal decline and disease. Apart from the role of basal autophagy on neuronal survival, growing evidence suggests its implication in the development of neuropsychiatric diseases and cognitive impairment in animal experimental models. Relative studies have associated neurodegeneration and certain neuropsychiatric disorders with autophagy impairment, accompanied by extensive protein aggregation. Moreover, autophagy upregulation has been linked to both improvement of neurodegenerative symptoms and mood stabilization in animals. Indeed, evidence suggests that macroautophagy, a specific form of autophagy, plays a major role on presynaptic neurotransmission and neuronal circuits, albeit through unknown mechanisms. Hence, neuronal autophagy is involved in numerous neuronal processes and identification of the relative underlying molecular mechanisms can lead to a better understanding of brain function and neuropsychiatric pathologies in humans. However, the way through which enhancement of neuronal autophagy affects specific brain domains, neuronal circuits, cognition, mood and behaviour is still obscure.
In this study we tested the effects of neuronal autophagic enhancement in flies and zebrafish. Combined behavioral and biochemical analysis revealed that acute and chronic autophagy induction at the brain impaired specific forms of memory and altered behavioral patterns in both species. We identified specific categories of nerve cells at specific brain domains where autophagy exerts its action, serving as coordinators of mood and cognition. We have characterized a neuronal circuit that is affected by autophagy – induced alterations on neurotransmitters transporters’ intracellular localisation, which target activity of specific postsynaptic receptors. Such alterations trigger c-AMP signalling activity, responsible for the autophagic effects on behaviour and cognition. Our results indicate that neuronal autophagy affects neuronal functionality through an evolutionary conserved mechanism, which also regulates developmental phenotypes in Drosophila.

Tuesday 11 June 2019 16:00 – 17:00 A. Payatakes Seminar Room

” FOG-1 interacts with CTCF and the cohesin complex in erythroid cells”

Dr. Grigorios Tsaknakis Institute of Molecular Biology and Biotechnology (IMBB)

Abstract
The Friend of GATA-1 (FOG) family of zinc finger proteins play essential roles in development and cell differentiation through physical interaction with GATA transcription factors. The specific interaction between FOG-1, a non-DNA binding, multi-zinc finger transcriptional co-factor, and GATA-1 is necessary for lineage specification towards the erythroid and megakaryocytic cell fates and is involved in both transcriptional activation and repression, potentially in the context of chromatin architecture reorganization. More specifically, FOG-1 and GATA-1 have been implicated in the spatial re-organization of ‘looped’ chromatin domains when activating the β-globin locus or when repressing the Kit locus during murine erythroid differentiation. In investigating the molecular basis of FOG-1/GATA1 functions, we used a biotinylation tagging approach in mouse erythroleukemic cells followed by mass spectrometry in order to characterize novel FOG-1 protein complexes. Apart from the known multi-protein complexes that FOG-1 recruits in association with GATA-1, such as the nucleosome remodeling domain (NuRD) complex and Cterminal binding protein (CTBP)-containing complex, we identified FOG-1 to be interacting with the transcriptional factor CTCF and the cohesin complex. Cohesins and CTCF are known to be implicated in the 3-dimensional organization of the genome and in delineating subdomains of gene activity in nuclear space. Validation experiments including streptavidin pulldown assays, immunoprecipitations and ChIP-reChIP assays in the mouse β-globin and c-Kit loci have confirmed these interactions. Moreover, we have recently generated ChIP-seq data for FOG-1 genome-wide occupancy profile in mouse erythroid cells and these data demonstrate overlapping as well as distinct patterns with GATA-1, CTCF and cohesins. These findings raise the intriguing prospect of functional crosstalk between a lineage-specific transcriptional complex (GATA1/FOG-1) and architectural transcription factors and structural chromosomal proteins in regulating cellspecific gene expression programs in differentiation.

Tuesday 4 June 2019 16:00 – 17:00 A. Payatakes Seminar Room

” Changes of PM2.5 concentrations and its sources during the last 20 years in the US”

Dr. Xakousti Skyllakou Institute of Chemical Engineering Sciences (ICE-HT)

Abstract
Quantification of the spatial and temporal variations in the sources of air pollutants, especially PM2.5, can inform control strategies and, potentially, the understanding of PM2.5 health effects. Three-dimensional chemical transport models (CTMs) are well suited to help address this problem, since they simulate all the major processes that impact PM2.5 concentrations and transport. In this study we quantify the changes in the concentration, composition, and sources of PM2.5 in the US from the early 1990s to the early 2010s.
The CTM PMCAMx is applied over US to together with the Particulate Source Apportionment Technology (PSAT) source apportionment algorithm. PSAT is used to quantify the contribution of seven source categories (on road transport, non-road transport, biogenic, electrical generation units (EGU) non EGU point sources, long-range transport from outside the domain and all other sources) to all the simulated primary and secondary PM components (and also gas-phase air pollutants) as a function of space and time. The same version of the CTM PMCAMx using consistent emissions and meteorology was used to simulate the changes in source contributions over two decades. The performance of the model was similar to those of its previous evaluation exercises in the same domain. The significant changes that have taken place in the contributions of the PM major sources during this extended period are highlighted.

Tuesday 21 May 2019 16:00 – 17:00 “Stelios Orphanoudakis” Seminar Room

“Unravelling novel genes that contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in mice”

Dr. Effie Thymiakou Institute of Molecular Biology and Biotechnology (IMBB)

Abstract
The number of people with non-alcoholic fatty liver disease (NAFLD) has increased dramatically in the past three decades imposing a substantial public health burden. Almost one third of NAFLD patients develop nonalcoholic steatohepatitis (NASH), a condition which is related to increased mortality due to the progression to cirrhosis and hepatocellular carcinoma. In addition, all NAFLD/NASH patients are at high risk of cardiovascular disease and type 2 diabetes (T2D). The need for improved diagnosis, treatment and management is evident but the efforts to develop efficient treatments are hindered by the combinatorial effect of genetic and environmental influences. Our aim is to develop new models of NAFLD that will enrich our knowledge on the pathogenesis of this disease and reveal potential therapeutic targets. For this purpose, we studied mice with liver-specific ablation of HNF4α (H4LivKO mice) which develop hepatic steatosis and show abnormal lipid homeostasis. We also studied the liver-specific HNF4α heterozygote mice (H4LivHet) which express lower levels of HNF4α in the liver in order to mimic the state found in NASH patients and investigate whether HNF4α can act as a predisposition factor for the development of NAFLD.