Biology subjects

Soliman, M.

Publications and source records attributed to Soliman, M..

4 recordsLinked to original sources

bioRxiv2024

Profiling Glioma Stem Cell Dynamics via 3D-based Cell Cycle Reporter Assays

Successful containment of unwanted cell cycle progression in tumours such as glioblastoma (GBM) requires targeted therapeutic approaches which rely on understanding cell cycle dynamics in response to microenvironmental stimuli. Glioma Stem Cells (GSCs) can drive tumour initiation, recurrence, therapy resistance, and are often attributed to the heterogeneity and plasticity of GBM. In vitro models using patient-derived GSCs provide a life relevant tool for exploration of complex molecular mechanisms underlying the aggressive characteristics of GBM. Introduction of 3D tissue culture systems permits the study of spatial complexity of the tumour mass and enables control over diverse conditions within the surrounding microenvironment. This chapter demonstrates detailed methods to study spatio-temporal changes to the cell cycle dynamics using available fluorescent cell cycle reporter systems in combination with bioinformatics-based signal intensity and localization analysis. We present a successful approach that investigates the 3D cell cycle dynamics of GSC populations. This approach utilizes GBM neurosphere and organoid cultures, which are assessed over time and under therapeutic pressure. These models can be further explored, manipulated, and customized to serve specific experimental designs.

cancer biology↗

bioRxiv2024

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8+ T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

cancer biology↗

bioRxiv2023

Multiepitope-based vaccine design against DiiA in Streptococcus pneumoniae, An immunoinformatics approach.

Streptococcus pneumoniae (SPN) infection has resulted in significant morbidity and mortality worldwide in children and adults. It is responsible for colonizing the human nasopharynx and can also cause diseases, including otitis media, pneumonia, bacteraemia, and meningitis. SPN is exhibiting resistance to multiple antibiotics and current vaccines have a number of limitations including poor immunogenicity and limited effectiveness against all pneumococcal serotypes. Here, we explain the design of a novel multi-epitope vaccine using Dimorphic invasion-involved protein A (DiiA) as a target protein. For designing the vaccine, the sequence of DiiA was obtained and various bioinformatics tools were employed to predict multiple CTL, HTL, B lymphocyte epitopes of DiiA. After evaluating antigenicity, allergenicity, toxicity, and immunogenicity, the most promising epitopes were chosen for constructing the vaccine, followed by an analysis of their physicochemical and immunological characteristics.The prediction, refinement, and validation of the 3D structure of the vaccine were carried out. Molecular docking, molecular dynamic simulation, and immune simulation were executed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptor (TLR4). Vaccine translation, codon optimization were performed and expression efficiency was assessed through an in-silico cloning experiment performed to transfer into pET28a(+) plasmid vector.The obtained results proved that the vaccine maintained structural stability and possessed the capability to stimulate an efficient immune response against S. pneumoniae infection. The constructed vaccine has the potential for subsequent wet lab experimentation, leading to the development of an innovative vaccine.

bioinformatics↗

bioRxiv2022

Coordinated control of neuronal differentiation and wiring by a sustained code of transcription factors

The enormous diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct neurons in the Drosophila visual system can each be defined by unique combinations of [~]10 transcription factors that are continuously expressed by them. We show that targeted modifications of this selector code induce predictable conversions of cell fates between neurons in vivo. These conversions appear morphologically and transcriptionally complete, arguing for a conserved gene regulatory program that jointly instructs both the type-specific development and the terminal features of neurons. Cis-regulatory sequence analysis of open chromatin links one of these selectors to an upstream patterning gene in stem cells that specifies neuronal fates. Experimentally validated network models show that selectors interact with ecdysone signaling to regulate downstream effectors controlling brain wiring. Our results provide a generalizable framework of how specific fates are initiated and maintained in postmitotic neurons.

neuroscience↗