Biology subjects

Tomazou, M.

Publications and source records attributed to Tomazou, M..

4 recordsLinked to original sources

bioRxiv2023

Oct4 is a gatekeeper of epithelial identity by regulating cytoskeletal dynamics in skin keratinocytes

Oct4 is a pioneer transcription factor regulating pluripotency. However, it is poorly known whether Oct4 has an impact on epidermal cells. We generated OCT4 knockout clonal cell lines using immortalized human skin keratinocytes to identify a functional role for the protein. Here we report that Oct4-deficient cells transitioned into a mesenchymal-like phenotype with enlarged size and shape, exhibited accelerated migratory behavior, decreased adhesion and appeared arrested at G2/M cell cycle checkpoint. Oct4 absence had a profound impact on cortical actin organization, with loss of microfilaments from cell membrane, increased puncta deposition in the cytoplasm and stress fiber formation. E-cadherin, {beta}-catenin and ZO1 were almost absent from cell-cell contacts while fibronectin deposition was markedly increased in ECM. Mapping of the transcriptional and chromatin profiles of Oct4-deficient cells revealed that Oct4 controls the levels of cytoskeletal, ECM and differentiation related genes, whereas epithelial identity is preserved through transcriptional and non-transcriptional mechanisms.

cell biology↗

bioRxiv2021

In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches

This study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence. We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obtained between March 2020 and January 2021, as well as all data available from GISAID. We combine this with countries regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of Cyprus-specific mutations are obtained by mutation tracking analysis. This entails calculating specific mutation frequencies within the Cypriot population and comparing these with their prevalence world-wide throughout the course of the pandemic. We further make use of linear regression models to extrapolate additional information that may be missed through standard statistical analysis. We report a single mutation found in the ORF1ab gene (S6059F) that appears to be significantly enriched within the Cypriot population. We further analyse this mutation using regression models to investigate possible associations with increased deaths and cases per million. Moreover, protein structure prediction tools show that the mutation infers a conformational change to the protein that significantly alters its structure when compared to the reference protein. Investigating Cyprus-specific mutations for SARS-CoV-2 can not only lead to important findings from which to battle the pandemic on a national level, but also provide insights into viral virulence worldwide.

bioinformatics↗

bioRxiv2020

Generalized linear models provide a measure of virulence for specific mutations in SARS-CoV-2 strains

This study aims to highlight SARS-COV-2 mutations which are associated with increased or decreased viral virulence. We utilize, genetic data from all strains available from GISAID and countries regional information such as deaths and cases per million as well as covid-19-related public health austerity measure response times. Initial indications of selective advantage of specific mutations can be obtained from calculating their frequencies across viral strains. By applying modelling approaches, we provide additional information that is not evident from standard statistics or mutation frequencies alone. We therefore, propose a more precise way of selecting informative mutations. We highlight two interesting mutations found in genes N (P13L) and ORF3a (Q57H). The former appears to be significantly associated with decreased deaths and cases per million according to our models, while the latter shows an opposing association with decreased deaths and increased cases per million. Moreover, protein structure prediction tools show that the mutations infer conformational changes to the protein that significantly alter its structure when compared to the reference protein.

bioinformatics↗

bioRxiv2017

Computational Re-Design of Synthetic Genetic Oscillators for Independent Amplitude and Frequency Modulation

Engineering robust and tuneable genetic clocks is a topic of current interest in Systems and Synthetic Biology with wide applications in biotechnology. Synthetic genetic oscillators share a common structure based on a negative feedback loop with a time delay, and generally display only limited tuneability. Recently, the dual-feedback oscillator was demonstrated to be robust and tuneable, to some extent, by the use of chemical inducers. Yet no engineered genetic oscillator currently allows for the independent modulation of amplitude and period. In this work, we demonstrate computationally how recent advances in tuneable synthetic degradation can be used to decouple the frequency and amplitude modulation in synthetic genetic oscillators. We show how the range of tuneability can be increased by connecting additional input dials, e.g. orthogonal transcription factors that respond to chemical, temperature or even light signals. Modelling and numerical simulations predict that our proposed re-designs enable amplitude tuning without period modulation, coupled modulation of both period and amplitude, or period adjustment with near-constant amplitude. We illustrate our work through computational re-designs of both the dual-feedback oscillator and the repressilator, and show that the repressilator is more flexible and can allow for independent amplitude and near-independent period modulation.

synthetic biology↗