Copper is an essential trace element tightly regulated within organisms, particularly in hepatocytes, where the ATPase Copper Transporting Beta protein (ATP7B) maintains homeostasis. Mutations in ATP7B result in Wilson disease (WD), causing harmful copper accumulation and organ dysfunction. Despite its importance, accurately measuring copper concentrations remains challenging due to low...
Background: Tbx1 function is involved in cardiac and pharyngeal development. Information regarding the genetic elements and molecular mechanisms that regulate the gene expression is still incomplete. We used in vitro differentiation, single cell biology, and bioinformatic tools to identify and validate regulatory elements of the gene.
Material and methods: We employed simultaneous single...
De-novo protein design allows a wider exploration of protein folding space than directed evolution and has been profitable employed in several fields of biochemistry and medicine, as metalloproteins design [1] and in-vitro diagnostics (IVD) [2]. Among other design tasks, de novo protein binders can now be obtained with high success-rate that are highly specific towards a series of biological...
Effective clinical genome interpretation relies on accurately distinguishing between benign and pathogenic rare variants. Current genome-wide trained variant prioritization tools often lack precision and may overlook key parameters defining gene-disease relationships. We hypothesized that developing predictors based on curated, disease-specific gene sets could significantly enhance the...
We have developed an innovative approach to simultaneously measure the volume of the cell and the volume of the nucleus in live cultured cells. Through this method, we have made a surprising discovery that challenges the conventional understanding of cellular growth. While the cytoplasm grows exponentially, in line with previous findings, we have found that the nucleus grows linearly. This...
Synthetic Biology aims at the design and implementation of novel, and more reliable, genetic circuits by employing engineering principles, with applications ranging from health treatments to bioremediation and production of drugs or biofuels. The use of biomolecular PID controllers is particularly appealing in this field as it allows achieving perfect robust adaptation via the integral action...
It has been recently discovered that SARS-CoV-2 alters chromatin 3D structure of the host genome [1] at multiple length scales, ranging from some kbp to entire chromosomes. We use polymer-physics models to investigate the physical mechanisms underlying such re-structuring. In particular, we show that a polymer model with altered chromatin phase-separation properties [3] accurately captures...
Neoadjuvant chemotherapy (NAC) plays an important role in the therapeutic strategy of locally advanced gastric cancer (GC). Unfortunately, the heterogeneous cellular and molecular nature of GC results in NAC resistance and subsequent loss of benefit in almost 50% of treated patients. Currently, predictive biomarkers to guide perioperative treatment drug selection, are still heterogeneous and...
Background.
Methylmalonic acidemia (MMA) is the most common form of organic acidemias, an heterogeneous group of rare inherited metabolic disorders that affect amino acid and protein metabolism. As suggested by their name, organic acidemias are characterized by the accumulation of organic acids at toxic concentrations. Isolated methylmalonic acidemia is caused by impaired...
Glycogen storage diseases are inherited disorders of carbohydrate metabolism resulting from the deficiency of individual enzymes involved in the synthesis, transport and breakdown of glycogen [1]. In particular, glycogen storage disease type Ia (GSDIa) is caused by deficient activity of glucose-6-phosphatase, which plays a key role in glucose homeostasis by hydrolysing glucose-6-phosphate...
Simulation of cell populations can be carried out by using parameters obtained from experimental cell cultures producing cells defined in terms of position, size or growth state. However representation of cell shape is desirable in order to better visualise the results as well as predicting interactions with the culture substrate or between bordering cells. Here we describe a procedure for...
Simulations are often used to analyse and dissect complex experimental systems where cells modify their behaviour while moving, growing and adapting to internal and external stimuli. A number of procedures and tools have been proposed aimed to model cell behaviour, ranging from whole cell mass simulation to lattice based models, where cells are represented by one or more lattice elements. More...
The microbiome plays a critical role in human health and has also become a key focus in the development of food products. Our understanding of these complex microbial communities has been improved thanks to recent advances in metagenomics and computational development that has enabled large-scale integrative analyses. In this talk, we will provide an overview of recent and ongoing research...
Introduction
Neuroblastoma (NB) is a pediatric malignancy originating from neural crest cells (NCCs) during sympathetic nervous system development. NB is a heterogeneous tumor composed by two distinct cell identities: the most differentiated adrenergic (ADRN) identity, and the most aggressive mesenchymal (MES) one. Perturbations in the activity of transcription factors (TFs) involved in...
The study of major biomolecules within cells, such as DNA, RNA, proteins,
and metabolites, has led to the emergence of various omics disciplines (genomics,
transcriptomics, proteomics, metabolomics) that generate vast volumes of data, known
as big omics data. Managing, analyzing, interpreting, sharing, and integrating this data
presents significant challenges in bioinformatics. This field...
DNA analysis has become fundamental to various fields, including disease treatment [1], outbreak surveillance [2], forensic investigations [3], and evolutionary studies [4]. The rise of large-scale genomics and advanced sequencing technologies, such as Oxford Nanopore Technologies, has led to an exponential increase in data generation, far surpassing Moore's Law [5]. By...
Immune functions have a general sex bias, with women showing stronger immune responses to pathogens and being more susceptible than men to autoimmune diseases. The presence of two X chromosomes has been widely associated with autoimmunity, independently of sex hormones. This might be explained by a failure of the mammalian sex-dosage compensation mechanism by which one of the two female X...
Neuroblastoma (NB) is a pediatric solid tumor, with a median diagnosis age of 18 months. Its presentation varies widely, ranging from low-risk tumors to aggressive disease in high-risk cases with a 5-year survival rate of 50%. Despite numerous identified genomic alterations, the current understanding of NB mutational landscape does not fully explain its heterogeneity.
We analyzed Whole Genome...
