Bilal Ahmad Makki’s Post

Bacteriophages (phages) are viruses that can infect and kill the bacterial hosts specifically. Interaction between phages and their bacterial hosts is important in molecular biology research and has been extensively studied for decades. In various environments, phages and bacteria work toward into an endless state of co-evolutionary competition and equilibrium. On the one hand, the high abundance of phages, which outnumber bacteria by approximately 10-fold, makes the encounter of bacteria and phage invaders possible in every ecosystem. To survive and/or escape phage predation, bacteria have evolved and acquired sets of resistance mechanisms, including prevention of phage adsorption to cell surfaces and subsequent injection of phage genomes, targeted cleavage of injected nucleic acids via restriction-modification (R-M) system and CRISPR/Cas system, and even suicide of phage-infected cells via abortive-infection (Abi) system. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes various infections mainly in immunocompromised individuals, especially for those suffering from burn wounds, cancer and cystic fibrosis. The notorious characteristics of metabolic versatility, biofilm formation, and drug resistance make P. aeruginosa-related infections very difficult to eradicate in clinical settings. Phages represent a promising alternative to traditional antibiotics for treating bacterial infections, particularly for multidrug-resistant and biofilm infections. Characterization of the structural details of phages constitutes an important effort to develop new therapeutics. Here you can see the crystal structure of the gp2 protein from the bacteriophage PA1c that infects Pseudomonas aeruginosa (PDB code: 7UYX) Rendering by Francisco J. Enguita made with #proteinimager https://lnkd.in/dbRC7cBM #molecularart #immolecular #phage #pseudomonas #infection #biofilm #pa1c #gp2 #xray

Bacteriophages (phages) are viruses that can infect and kill the bacterial hosts specifically. Interaction between phages and their bacterial hosts is important in molecular biology research and has been extensively studied for decades. In various environments, phages and bacteria work toward into an endless state of co-evolutionary competition and equilibrium. On the one hand, the high abundance of phages, which outnumber bacteria by approximately 10-fold, makes the encounter of bacteria and phage invaders possible in every ecosystem. To survive and/or escape phage predation, bacteria have evolved and acquired sets of resistance mechanisms, including prevention of phage adsorption to cell surfaces and subsequent injection of phage genomes, targeted cleavage of injected nucleic acids via restriction-modification (R-M) system and CRISPR/Cas system, and even suicide of phage-infected cells via abortive-infection (Abi) system. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes various infections mainly in immunocompromised individuals, especially for those suffering from burn wounds, cancer and cystic fibrosis. The notorious characteristics of metabolic versatility, biofilm formation, and drug resistance make P. aeruginosa-related infections very difficult to eradicate in clinical settings. Phages represent a promising alternative to traditional antibiotics for treating bacterial infections, particularly for multidrug-resistant and biofilm infections. Characterization of the structural details of phages constitutes an important effort to develop new therapeutics. Here you can see the crystal structure of the gp2 protein from the bacteriophage PA1c that infects Pseudomonas aeruginosa (PDB code: 7UYX) Rendering by Francisco J. Enguita made with #proteinimager https://lnkd.in/dfJcVb4C #molecularart #immolecular #phage #pseudomonas #infection #biofilm #pa1c #gp2 #xray

A very informative paper using cryo-EM to obtain near-atomic structure of Ff phage! The Ff phage has long been harnessed for biomedical research and drug discovery, notably in phage display. However, its complete structure and precise biological mechanism have remained elusive. This paper now presents new structural insights into Ff phage infection, assembly, and egress. These findings hold the potential to advance technologies requiring genetically engineered phage, such as Phage-Assisted Continuous Evolution (PACE) and unconventional phage display. Even if you're not into phage, you should still check out the cool images and videos of this amazing creation of nature! https://lnkd.in/egJjncwc

#newscience alert! Catch up on all the #publications from our department last month (December 2023) and learn about sperm, cell division, gene editing and more! 🤝 Regulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome https://lnkd.in/ez42j-py Jeremy Luban, James Munro ✂ Self-delivering, chemically modified #CRISPR RNAs for AAV co-delivery and genome editing in vivo https://lnkd.in/ecpbBk5Q Jonathan Watts 👩🔬 Dynamic stability of Sgt2 enables selective and privileged client handover in a chaperone triad https://lnkd.in/evAT6yi2 Yumeng Liu 🎁 Revisiting #chromatin packaging in mouse sperm https://lnkd.in/ePQ3hQaC Chih-Hsiang Yang, Oliver Rando, Qiangzong Yin, Olga Strelkova 🤔 RNA-mediated symmetry breaking enables singular olfactory receptor choice https://lnkd.in/esiBWZXU Houda Belaghzal , PhD, Job Dekker 🌟 A Fluorescent Reporter Mouse for In Vivo Assessment of Genome Editing with Diverse Cas Nucleases and Prime Editors https://lnkd.in/ebR72KUh Jonathan Watts 🤰 Food, nutrition, and #fertility: from soil to fork https://lnkd.in/efzSe96a Oliver Rando 🤒 Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA https://lnkd.in/eVfc-hYa Leonard Barasa, Ph.D., Paul Thompson 🚗 Nano-optogenetic CAR-T Cell #Immunotherapy https://lnkd.in/e6zQeJJ3 Gang Han 😵 A neuronal coping mechanism linking stress-induced #anxiety to motivation for reward https://lnkd.in/eN5zHA2n Leonora Martínez-Núñez, PhD 🤒 Citrullination profile analysis reveals peptidylarginine deaminase 3 as an HSV-1 target to dampen the activity of candidate #antiviral restriction factors https://lnkd.in/eyVK-zgj Sudeshna Sen, Leonard Barasa, Ph.D., Hafeez Haniff, Paul Thompson #Preprints 🤒 IFIH1 (MDA5) is required for innate immune detection of intron-containing RNA expressed from the #HIV-1 provirus https://lnkd.in/e3qj-Da2 Jeremy Luban 🍩 Differences in clamp loader mechanism between bacteria and eukaryotes https://lnkd.in/ec_eyPVR Joshua Pajak, Emily Norman, Emma Sedivy, Jacob Landeck, Brian Kelch

Release your inner M1 M2 Macrophage and Check this new paper by Dr Federica Orsenigo in my lab published today in Cell reports. Who should read it: -Anyone working with human monocytes needing to measure them, identify them or isolate them. We do it with CSF1R! -Anyone interested in M1 M2 Macrophage activation and is looking for a robust multi-gene tool to study how drugs, antibodies or even diseases alter their activation in response to the 4 horses of the innate immunity apocalypse: LPS, IFNg, IL-4 and steroids. -Anyone curious about what we mean about Macrophage Mosaicism. Happy to chat about this with any user interested in knowing more. Would be good to re-educate some macrophages together.

Innate immunity plays a vital role in xenotransplantation. A CD47 molecule, binding to the SIRPα expressed on monocyte/macrophage cells, can suppress cytotoxicity. Particularly, the SIRPα contains ITIM, which delivers a negative signal. Our previous study demonstrated that the binding between CL-P1 and surfactant protein-D hybrid (CL-SP-D) with SIRPα regulates macrophages' phagocytic activity. In this study, we examined the effects of human CD47 and CL-SP-D expression on the inhibition of xenograft rejection by neutrophils in swine endothelial cells (SECs).

📃Scientific paper: Antibacterial, antibiofilm, and anti-quorum sensing activities of pyocyanin against methicillin-resistant Staphylococcus aureus: in vitro and in vivo study Abstract: Background Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered a major public health problem, as the treatment options are restricted. Biofilm formation and the quorum sensing (QS) system play a pivotal role in S. aureus pathogenicity. Hence, this study was performed to explore the antibacterial effect of pyocyanin (PCN) on MRSA as well as its effect on MRSA biofilm and QS. Results Data revealed that PCN exhibited strong antibacterial activity against all test MRSA isolates ( n  = 30) with a MIC value equal to 8 µg/ml. About 88% of MRSA biofilms were eradicated by PCN treatment using the crystal violet assay. The disruption of MRSA biofilm was confirmed using confocal laser scanning microscopy, which showed a reduction in bacterial viability (approximately equal to 82%) and biofilm thickness (approximately equal to 60%). Additionally, the disruption of the formation of microcolonies and the disturbance of the connection between bacterial cells in the MRSA biofilm after PCN treatment were examined by scanning electron microscopy. The 1/2 and 1/4 MICs of PCN exerted promising anti-QS activity without affecting bacterial viability; Agr QS-dependent virulence factors (hemolysin, protease, and motility), and the expression of agrA gene, decreased after PCN treatment. The in silico analysis confirmed the binding of PCN to the AgrA protein active site, which blocked its action. The in vivo study using the rat wound infection model confirmed the ab... Discover the rest of the scientific article on es/iode ➡️https://etcse.fr/3Hkb

Parkinson’s disease (PD)-relevant protein pathological alpha-synuclein triggers disruption of proteostasis and subsequently augment global protein synthesis via activation of mTOR complex (mTORC1), leading to neurodegeneration in PD. Genetic and pharmacological inhibition of mTOR rescued pathologic alpha-synuclein-induced loss of dopamine neurons, behavioral abnormalities and aberrant biochemical signaling in sporadic PD-relevant alpha-synuclein pre-formed fibril mouse model and Drosophila transgenic model. Proud to be a part of this exciting study!

Extracellular nucleotides are important mediators of activation, triggering various responses through plasma membrane P2 and P1 receptors. P2 receptors are further subdivided into ionotropic P2X receptors and G protein-coupled P2Y receptors. P2X4 is an ATP-gated cation channel broadly expressed in most tissues of the body. Within the P2X family, P2X4 has a unique subcellular distribution, being preferentially localized in lysosomes. In these organelles, high ATP concentrations do not trigger P2X4 because of the low pH. However, when the pH increases to 7.4, P2X4 can be stimulated by intra-lysosomal ATP, which is in its active, tetra-anionic form. P2X7-dependent activation of inflammasomes, leading to increased release of IL-1β and IL-18. The role of P2X4 in various diseases could be beneficial or deleterious even though the pathophysiological mechanisms involved are still poorly defined. However, in diseases whose physiopathology involves activation of the NLRP3 inflammasome, P2X4 was found to exacerbate severity of disease. The recent production of monoclonal antibodies specific for the human and mouse P2X4, some of which are endowed with agonist or antagonist properties, raises the possibility that they could be used therapeutically. Analysis of single nucleotide polymorphisms of the human P2RX4 gene has uncovered the association of P2RX4 gene variants with susceptibility to several human diseases. Here you can see a cryoEM structure of the zebrafish P2X4 receptor, used as a model to understand the function of the human protein (PDB code: 8JV5) Rendering by Francisco J. Enguita made with #proteinimager https://lnkd.in/d5i3QiWG #molecularart #receptor #zebrafish #P2X4 #model #nucleotide #cryoem

👨🔬 Understanding the structure, including multiple conformational states, of #SLCs can be vital to understanding various disease modalities, however #membraneproteins are historically challenging to study. In the study "Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2" Hu, W. et al. reveal high-resolution structures of SLC26A2 in complex with its substrates. 🎯 The authors highlight the role of sulfate ion (SO42-) in human physiology, facilitating cellular growth and hormone regulation through sulfate conjugation, focusing on the #SLC26A2 #transporter, which actively manages SO42− levels and other anions like Cl− across tissues, revealed with #cryoEM. These structures, supported by molecular dynamics simulations and mutational analysis, clarify the molecular interactions and anion exchange mechanisms of SLC26A2, illustrating how it influences health conditions like Crohn's disease and colon cancer. 💡 Their findings underscore SLC26A2's involvement in genetic disorders, with pathogenic mutations linked to severe developmental diseases. By mapping these mutations onto the high-resolution structures, this study provide insights into their impact on transporter function, emphasizing SLC26A2's potential as a therapeutic target in related diseases, enhancing our understanding of its structural dynamics and physiological roles. 📖 Read the study: https://lnkd.in/gAFMBcEU