Biology subjects

Iuliani, I.

Publications and source records attributed to Iuliani, I..

3 recordsLinked to original sources

bioRxiv2025

Sex-specific disease association and genetic architecture of retinal vascular traits

Sex as a biological variable (SABV) remains underemphasized in biomedical research, despite its well-established impact on disease prevalence, progression, and genetic architecture. Here, we investigated sex differences in retinal vascular phenotypes, which are emerging as non-invasive biomarkers for ocular, cardiovascular, and neurodegenerative diseases. We used both interaction and sex-stratified analyses in disease association and genome-wide association studies (GWAS), including the X chromosome. Our analyses revealed sex-specific differences in associations between retinal traits, cardiometabolic risk factors, and disease outcomes. Several phenotypes showed prognostic value for mortality and cardiovascular endpoints, predominantly in one sex, illustrating the limitations of sex-agnostic analyses. Genetic analyses revealed differences in genetic architectures, with females exhibiting higher heritability and a greater number of associated loci, as well as sex-specific trait-gene associations. Notably, we report the first genetic association on the X chromosome for retinal vascular phenotypes. These findings suggest sex-differential genetic and environmental contributions to microvascular morphology, possibly reflecting divergent biological pathways and risk profiles. Our study underscores the necessity of integrating SABV and sex-aware approaches in genetic and prognostic research to advance precision medicine and improve tailored risk stratification.

genetics↗

bioRxiv2023

Direct single-cell observation of a key E. coli cell cycle oscillator

A long-standing hypothesis sees DNA replication control in E. coli as a central cell cycle os-cillator at whose core is the DnaA protein. The consensus is that the activity of the DnaA protein, which is dependent on its nucleotide bound state, is an effector of initiation of DNA replication and a sensor of cell size. However, while several processes are known to regulate DnaA activity as a function of the cell cycle, the oscillations in DnaA expression and DnaA ac-tivity have never been observed at the single cell level, and their correlation with cell volume has yet to be established. In this study, we measured the volume-specific production rate of a reporter protein under control of the dnaAP2 promoter in single cells. By a careful dissection of the effects of DnaA-ATP-and SeqA-dependent regulation, two distinct cell cycle oscilla-tors emerge. The first oscillator, driven by gene dosage, DnaA activity and SeqA repression oscillates synchronously, and shows a causal relationship, with cell size and divisions, sim-ilarly to initiation events. The second one, a reporter of dosage and DnaA activity only, is strongly coupled to cell size, but loses the synchrony and causality properties, suggesting that DnaA activity peaks do not correspond directly to initiation events. These findings suggest that while transcription regulation by DnaA activity performs volume sensing, transient in-hibition of gene expression by SeqA following replication fork passage keeps DnaA activity oscillations in phase with initiation events.

cell biology↗

bioRxiv2019

Early fate of exogenous promoters in E. coli

Gene gain by horizontal gene transfer is a major pathway of genome innovation in bacteria. The current view posits that acquired genes initially need to be silenced and that a bacterial chromatin protein, H-NS, plays a role in this silencing. However, we lack direct observation of the early fate of a horizontally transferred gene to prove this theory. We combine sequencing, flow cytometry and sorting, and microscopy to monitor gene expression and its variability after large-scale random insertions of a reporter gene in a population. We find that inserted promoters have a wide range of gene-expression variability related to their location. We find that high-expression clones carry insertions that are not correlated with H-NS binding. Conversely, binding of H-NS correlates with silencing. Finally, while most promoters show a common level of extrinsic noise, some insertions show higher noise levels. Analysis of these high-noise clones supports a scenario of switching due to transcriptional interference from divergent ribosomal promoters. Altogether, our findings point to evolutionary pathways where newly-acquired genes are not necessarily silenced, but may immediately explore a wide range of expression levels to probe the optimal ones.

genomics↗