An integrated view of the structure and function of the human 4D nucleome.

The dynamic three-dimensional (3D) organization of the human genome (the "4D Nucleome") is closely linked to genome function. Here, we integrate a wide variety of genomic data generated by the 4D Nucleome Project to provide a detailed view of human 3D genome organization in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We provide extensive benchmarking of 3D genome mapping assays and integrate these diverse datasets to annotate spatial genomic features across scales.

Use of in silico approaches, synthesis and profiling of Pan-filovirus GP-1,2 preprotein specific antibodies.

Intermolecular interactions of protein-protein complexes play a principal role in the process of discovering new substances used in the diagnosis and treatment of many diseases. Among such complexes of proteins, we have to mention antibodies; they interact with specific antigens of two genera of single-stranded RNA viruses belonging to the family Filoviridae-Ebolavirus and Marburgvirus; both cause rare but fatal viral hemorrhagic fever in Africa, with pandemic potential. In this research, we conduct studies aimed at the design and evaluation of antibodies targeting the filovirus glycoprotein precursor GP-1,2 to develop potential targets for the pan-filovirus easy-to-use rapid diagnostic tests.

immune evaluation of adenoviral vector-based platform for infectious diseases.

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes.

Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model.

Introduction: Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody.

Multi-scale phase separation by explosive percolation with single-chromatin loop resolution.

The 2 m-long human DNA is tightly intertwined into the cell nucleus of the size of 10 μm. The DNA packing is explained by folding of chromatin fiber. This folding leads to the formation of such hierarchical structures as: chromosomal territories, compartments; densely-packed genomic regions known as Topologically Associating Domains (TADs), or Chromatin Contact Domains (CCDs), and loops.

Genomic Marks Associated with Chromatin Compartments in the CTCF, RNAPII Loop and Genomic Windows.

The nature of genome organization into two basic structural compartments is as yet undiscovered. However, it has been indicated to be a mechanism of gene expression regulation. Using the classification approach, we ranked genomic marks that hint at compartmentalization.

Intermingling of chromosome territories.

The importance of higher order nuclear structure and compartmentalization for the control of the cell life is now indisputable. The genome of higher eukaryotes is organized into definite chromosome territories, and the three-dimensional organization of these territories may be intently related to genomic function, global regulation of gene expression, and even formation of exchange aberrations. In this review, we discuss our current understanding of the chromosome territories phenomenon and briefly describe how genes relocation in three-dimensional arrangement of the genome may influence their functioning.

The structural variability of the influenza A hemagglutinin receptor-binding site.

Hemagglutinin (HA) is a transmembrane protein of the influenza A virus and a key component in its life cycle. The protein allows the virus to enter a host cell by recognizing specific glycans attached to transmembrane proteins of the host, which leads to viral endocytosis. In recent years, significant progress has been made in understanding the structural relationship between changes in the HA receptor-binding site (RBS) and the sialylated glycans that bind them.

3DFlu: database of sequence and structural variability of the influenza hemagglutinin at population scale.

The influenza virus type A (IVA) is an important pathogen which is able to cause annual epidemics and even pandemics. This fact is the consequence of the antigenic shifts and drifts capabilities of IVA, caused by the high mutation rate and the reassortment capabilities of the virus. The hemagglutinin (HA) protein constitutes the main IVA antigen and has a crucial role in the infection mechanism, being responsible for the recognition of host-specific sialic acid derivatives.

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts.

Human DIS3, the nuclear catalytic subunit of the exosome complex, contains exonucleolytic and endonucleolytic active domains. To identify DIS3 targets genome-wide, we combined comprehensive transcriptomic analyses of engineered HEK293 cells that expressed mutant DIS3, with Photoactivatable Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) experiments. In cells expressing DIS3 with both catalytic sites mutated, RNAs originating from unannotated genomic regions increased ∼2.

Probabilistic approach to predicting substrate specificity of methyltransferases.

We present a general probabilistic framework for predicting the substrate specificity of enzymes. We designed this approach to be easily applicable to different organisms and enzymes. Therefore, our predictive models do not rely on species-specific properties and use mostly sequence-derived data.

The spirit of competition: to win or not to win.

A competition is a contest between individuals or groups. The gain is often an award or recognition, which serves as a catalyst to motivate individuals to put forth their very best. Such events for recognition and success are part of many International Society for Computational Biology (ISCB) Student Council Regional Student Groups (RSGs) activities.

Genomic positions of co-expressed genes: echoes of chromosome organisation in gene expression data.

Background: The relationships between gene expression and nuclear structure, chromosome territories in particular, are currently being elucidated experimentally. Each chromosome occupies an individual, spatially-limited space with a preferential position relative to the nuclear centre that may be specific to the cell and tissue type. We sought to discover whether patterns in gene expression databases might exist that would mirror prevailing or recurring nuclear structure patterns, chromosome territory interactions in particular.

Novel higher-order epigenetic regulation of the Bdnf gene upon seizures.

Studies in cultured cells have demonstrated the existence of higher-order epigenetic mechanisms, determining the relationship between expression of the gene and its position within the cell nucleus. It is unknown, whether such mechanisms operate in postmitotic, highly differentiated cell types, such as neurons in vivo. Accordingly, we examined whether the intranuclear positions of Bdnf and Trkb genes, encoding the major neurotrophin and its receptor respectively, change as a result of neuronal activity, and what functional consequences such movements may have.

A novel protein kinase-like domain in a selenoprotein, widespread in the tree of life.

Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised.

A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins.

Background: Peroxide turnover and signalling are involved in many biological phenomena relevant to human diseases. Yet, all the players and mechanisms involved in peroxide perception are not known. Elucidating very remote evolutionary relationships between proteins is an approach that allows the discovery of novel protein functions.