My group is studying the mechanistic basis of epigenetic regulation in the Polycomb system, a vital epigenetic silencing pathway that is widely conserved from flies to plants to humans. We use the process of vernalization in plants in our experiments, which involves memory of winter cold to permit flowering only when winter has passed via quantitative epigenetic silencing of the floral...
In recent years, the success of and insight gained by classical molecular modeling, in understanding the fundamentals of complex molecular phenomena, have triggered a strong desire to go beyond the limitations of the information that can be extracted from classical Molecular Dynamics MD, especially the limitations that cannot be resolved by advances in computational efficiency. To this aim...
8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a major product of the DNA oxidization process, has been proposed to have an epigenetic function in gene regulation and has been associated with genome instability. NGS-based methodologies are contributing to the characterization of the 8-oxodG role in many genome-related functions. However, the number of studies addressing the 8-oxodG epigenetic...
Gastric cancer (GC) remains one of the major causes of cancer-related mortality worldwide. Molecular heterogeneity is a major determinant for the clinical outcomes and an exhaustive tumor classification is currently missing. Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies, nevertheless shows unique characteristics in several tumor types,...
Background and rationale. Human tumors are complex systems characterized by molecular, cellular and spatial diversities. The totality of features demonstrating differences within a tumor is termed intra-tumor heterogeneity (ITH). ITH may be one of the mechanisms at the basis of the drug resistance and relapse triggered, for example, via the selection of malignant clones. Single cell...
Reactivation of the inactive X-chromosome (Xi) has been used to model epigenetic reprogramming in the mouse. Human studies have, however, been hampered by Xi epigenetic instability in pluripotent stem cells and difficulties in tracking emerging iPSCs. Recently, we have shown that reprogramming female human fibroblast via mouse ESC fusion recapitulates features of in vivo human naïve...
Automatic analysis of rodent behavior has been receiving growing attention in recent years, since rodents have been the reference species for many neuroscientific studies. In parallel, a number of technologies have been developed in a bid to automate the data interpretation. Thanks to the Digital Ventilated Cage (DVC by Tecniplast), a system relying on the detection of animal activity via the...
Blood is a complex fluid with non-Newtonian characteristics. It consists primarily of a concentrated suspension of deformable red blood cells (RBCs) [1] which tend to aggregate reversibly in microstructures, such as rouleaux; this tendency is a major contributor to the viscoelastic flow behavior of blood. Human blood mechanical response is strongly affected by RBC properties, such as volume...
Bardet-Biedl syndrome (BBS) is a ciliopathy genetic disorder characterized in most cases by obesity, polydactyly, renal dystrophy and cystic kidneys. BBS is strictly related to the hetero-octameric protein complex named as BBSome. The recruitment of BBSome into cilia membranes is mediated by the binding with the GTP binding protein ARL6, which binds at the interface between the BBS1 and BBS7...
Understanding intratumor heterogeneity and the interactions between tumor cells and the immune system is the critical step in the study of tumor growth and evolution. Typically in these studies a large number of unsorted cells from tumor biopsies are subject to Single-cell RNA sequencing (scRNA-seq) and then classified as malignant cells, stromal cells, and immune cells.
The...
Synthetic Biology aims at engineering biological systems with new functionalities, with applications ranging from health treatments to bioremediation, production of biofuels and drugs in bioreactors. This is made possible by embedding artificial genetic circuits into living cells, such as bacteria, yeast, and fungi, modifying their natural behavior; that is, by synthetically modifying when and...
The list of known exoplanets is rapidly growing (almost 5000 at the moment), but we know only an handful of rocky planets in their circumstellar habitable zone. We propose a revision of the criteria for defining the habitable zone, based on the updated knowledge of the role and diffusion of biometals, and present updated results on the statistics of Earth-like planets in the Galaxy.
Background | Neuroblastoma is a paediatric tumour of the peripheral sympathetic nervous system originating from the neural-crest cells. It is the second most common childhood solid cancer and its cure remains a challenge. In recent years, next generation sequencing of neuroblastoma has documented low somatic mutation rates and few recurrently mutated genes. As a result, the search for...
Genomic Medicine (GM) is an interdisciplinary medical specialty, whose goal is applying genomic information to clinics and research. Genome data, such as those generated by microarray (MA) and next generation sequencing (NGS), are natively digital and thus well suited for computational analysis and sharing. Nonetheless, their volume and complexity require ad hoc computational approaches and...
Peptide Nucleic Acids (PNAs), introduced by Nielsen et al. in 1991, are synthetic DNA/RNA analogues and represent a promising tool for gene modulation in anticancer treatment[1]. In the PNA structure, repetitive N-2-aminoethyl-glycine units replace the traditional sugar-phosphate DNA backbone, and the polyamide chain is connected to nucleobase covalently via carboxymethyl spacer. Thanks to...
In recent years, mathematical models are providing fundamental support in cancer research. By accounting for various biological and physical processes, these models can reveal insights into the dynamics of tumour growth and invasiveness, thereby allowing the development of pharmacological strategies to control tumour proliferation and invasion. The use of these tools is becoming increasingly...
Aberrant expression of transcriptional regulators can affect oncogenic gene expression programs in cancer. Mutations in the tumor suppressor TP53 (p53) are commonly found in UV-damaged skin and are thought to protect damaged epidermal cells from senescence and or oncogene-induced apoptosis, favoring cancer formation. In contrast, the other p53 family members TP63 (p63) and TP73 (p73) are...
CDC25 phosphatases (CDC25S) are members of the family of dual-specificity phosphatases (DSPs) and play a critical role in the regulation of the cell cycle. The overexpression of CDC25s in many human cancers supports their clinical significance and has encouraged the pursuit of specific small-molecule inhibitors. Unfortunately, there are currently no available CDC25 inhibitors with clinical...
The "Omics Sciences" have revolutionized modern biology. To date, there is no scientific field, from medicine to environmental sciences, passing through biochemistry and pharmacology that does not resort to these sciences for the study of complex biological systems.
Proteomics among these fields aims to study the entire set of constitutive proteins of a tissue, an organism in specific moment...
Computational protein design has collected many successes in recent years,1,2 however de novo proteins with a tetrathiolate mononuclear metal site have never been characterized both in structure and function. In this case, the selection of the first and second sphere of the iron center able to purposely induce a chosen redox potential is still a difficult task3. Besides...
DNA methylation is one of the most studied epigenetic modifications, with an established role in regulating gene expression and genome stability. It consists of enzyme mediated addition of a methyl-group to DNA bases. By acting in concert with other epigenetic marks, DNA methylation shapes the fate and engraves the identity of a cell. Its dysregulation has been linked to pathological...
The schematization of DNA structure can be tested by the Chern–Simons theory, that is a topological field theory mostly considered in the context of effective gravity theories. By means of the expectation value of the Wilson Loop, derived from this analogue gravity approach, it is possible to find the point-like curvature of genomic strings in KRAS human gene and COVID-19 sequences,...
Molecular Dynamics (MD) is a powerful computational technique used to understand the physical basis of the structure and function of biological systems.[1] In this context, coarse-grained (CG) models have been successfully applied to a broad range of bio-molecular systems, including the self-assembly of lipids in aqueous solutions. However, many biologically relevant processes occur on...
Cancer is a genetic disease resulting from the accumulation of genomics alterations in living cells. Large scale genomics studies have been instrumental to understand the recurrent somatic genetic
alterations within a cell, including chromosome translocations, single base substitutions, and copy-number alterations and for the characterization of their functional effects in transformed...
Motivation: DNA methylation is an epigenetic modification, primarily occurring at CpG sites, that is involved in major biological mechanisms, such as the regulation of gene expression and the genome stability. Typically, association studies based on this modification are focused on the identification of genomic regions whose average DNA methylation differs among distinct conditions. However,...
