Biology subjects

Mirsaeidi, M.

Publications and source records attributed to Mirsaeidi, M..

6 recordsLinked to original sources

bioRxiv2026

Comparative genomics and structure-informed analysis identify a putative tandem receptor-binding module in Pseudomonas phage UF_RH1

Abstract Bacteriophage receptor-binding proteins (RBPs) determine host recognition and host range but are frequently missed by conventional annotation because they evolve rapidly and often lack recognizable sequence domains. Pseudomonas phage UF_RH1 is a lytic Septimatrevirus with a 42,567 bp double-stranded DNA genome encoding 57 predicted open reading frames, several of which remain annotated as hypothetical proteins. Here, we reanalyzed the UF_RH1 distal-tail region using comparative synteny, phage RBP specific prediction tools, structure-informed domain analysis, oligomeric-symmetry prediction, and independent physicochemical calculations. Two adjacent proteins, WCF59042.1 (317 aa) and WCF59043.1 (320 aa), emerged as the strongest candidates for functional reannotation. WCF59042.1 was classified by DepoScope as a tail-spike protein with probability 1.00 and contains a high confidence C terminal tail-spike-associated segment spanning residues 210 to 317. WCF59043.1 was independently classified as a tail-spike candidate by RBPdetect2 (probability 0.51) and showed a strong Seq2Symm prediction for C3 homo-trimeric symmetry (0.990). Comparative genomic analysis places these proteins at positions corresponding to DLP2 gp22 and gp23, two similarly sized hypothetical virion proteins immediately downstream of the tape measure gene in a conserved distal-tail morphogenesis cassette. Because the closely related phages DLP1 and DLP2 use type IV pili for adsorption, we propose a testable model in which WCF59042.1 functions as a proximal connector/adaptor and WCF59043.1 contributes a distal trimeric receptor binding element. The model is computational and does not establish direct binding to PilA or assembled pili. Together, the convergent sequence, structural, oligomeric, and syntenic evidence supports a previously unrecognized tandem distal tail receptor-binding module in UF_RH1 and provides experimentally tractable targets for defining Septimatrevirus adsorption and host range.

microbiology↗

bioRxiv2021

Impacts of 203/204: RG>KR mutation in the N protein of SARS-CoV-2

We present a structure-based model of phosphorylation-dependent binding and sequestration of SARS-CoV-2 nucleocapsid protein and the impact of two consecutive amino acid changes R203K and G204R. Additionally, we studied how mutant strains affect HLA-specific antigen presentation and correlated these findings with HLA allelic population frequencies. We discovered RG>KR mutated SARS-CoV-2 expands the ability for differential expression of the N protein epitope on Major Histocompatibility Complexes (MHC) of varying Human Leukocyte Antigen (HLA) origin. The N protein LKR region K203, R204 of wild type (SARS-CoVs) and (SARS-CoV-2) observed HLA-A*30:01 and HLA-A*30:21, but mutant SARS-CoV-2 observed HLA-A*31:01 and HLA-A*68:01. Expression of HLA-A genotypes associated with the mutant strain occurred more frequently in all populations studied. ImportanceThe novel coronavirus known as SARS-CoV-2 causes a disease renowned as 2019-nCoV (or COVID-19). HLA allele frequencies worldwide could positively correlate with the severity of coronavirus cases and a high number of deaths.

bioinformatics↗

bioRxiv2020

Inborn errors E778K and G908R in NOD2 gene increase risk of nontuberculous mycobacterial infection: a computational study

BackgroundThe innate immune system has a critical role in the early detection of pathogens, mainly by relying on pattern-recognition receptor (PRR) signaling molecules. Nucleotide-binding oligomerization domain 2 (NOD2) is a cytoplasmic sensor for recognition of invading molecules and danger signals inside the cells. NOD2s functions are critical; polymorphisms of its encoding gene are associated with several immune pathological conditions. We recently reported that missense E778K and G908R variants of NOD2 gene are associated with recurrent pulmonary nontuberculous mycobacterial infections MethodsThis is an in-silico analysis of NOD2 gene using SNPs functionality analyses, post-translational modification site prediction and network analysis. ResultsOur analysis revealed that these damaging mutations affect the structural properties and function and ligand binding in the mutant receptor. ConclusionThe consequence of these mutations may also impress downstream processing and receptor crosstalk with other immune molecules and therefore increase susceptibility to infectious disease.

genetics↗

bioRxiv2020

Novel Three-Dimensional Organoid Sarcoidosis Granuloma Model

Sarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. This article presents the development of a novel in vitro three-dimensional lung-on-chip organoid designed to mimic granuloma formation. A lung on chip fluidic macrodevice with three channels for cell culture insertion was developed and added to the previously developed a lung-on-membrane model. Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface (ALI) of the microchip to create a three-dimensional organoid sarcoidosis model (OSGM). The model was tested for cell viability with fibroblasts. We measured the cytokine profiles in medium of OSGM and compared with lung model without granuloma. Concentration of IL-1beta, Il-6, GM-CSF, and IFN-gamma were found significantly higher in OSGM group. The current model represents the first 3D OSGM created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its ALI.

immunology↗

bioRxiv2020

Mutation in position of 32 (G>U) of S2M differentiate human SARS-CoV2 from Bat Coronavirus

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic pathogen that has rapidly mutated and become transmissible to humans. There is little existing data on the mutations in SARS-CoV-2 and the impact of these polymorphisms on its transmission and viral load. In this study, the SARS-CoV-2 genomic sequence was analyzed to identify variants within the 3UTR region of its cis-regulatory RNA elements. A 43-nucleotide genetic element with a highly conserved stem-loop II-like motif (S2M), was discovered. The research revealed 32 G>U and 16 G>U/A mutations located within the S2M sequence in human SARS-CoV-2 models. These polymorphisms appear to make the S2M secondary and tertiary structures in human SARS-CoV-2 models less stable when compared to the S2M structures of bat/pangolin models. This grants the RNA structures more flexibility, which could be one of its escape mechanisms from host defenses or facilitate its entry into host proteins and enzymes. While this S2M sequence may not be omnipresent across all human SARS-CoV-2 models, when present, its sequence is always highly conserved. It may be used as a potential target for the development of vaccines and therapeutic agents.

microbiology↗

bioRxiv2020

Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis

Growth hormone releasing hormone (GHRH) is a potent stimulator of GH secretion from the pituitary gland. Although GHRH is essential for the growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remains unknown. Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA602 (a GHRH antagonist) in two in vitro human granuloma models and an in vivo granuloma model. MIA602 decreases levels of IL2, IL12, and IL17A in in vitro granuloma model. We show further that the anti-inflammatory effect of MIA602 appears to be mediated by reduction in CD45++CD68+ cells in granulomatous tissue and upregulation in PD-1 expression in macrophages. In analysis of expression of proteins involved in the mitochondrial stage of apoptosis, we show that MIA602 increases the levels of caspase 3, BCL-xL/BAK dimer, and MCl-1/Bak dimer in granuloma. These findings indicate that MIA602 may not induce apoptosis. The clinical relevance of our findings further suggest that HGRH-R is potentially a target for treatment of granulomatous disease and MIA602 possibly a novel therapeutic agent for sarcoidosis.

immunology↗