Publications by authors named "Robert B Sim"
Article Synopsis
- The classical pathway of the complement system is initiated when C1q binds to target activators, including immune complexes, while factor H primarily regulates the alternative pathway but can also influence the classical pathway by competing for binding sites with C1q.
- Both C1q and factor H can recognize and bind to foreign or altered-self materials, including fibrin clots, which can activate the classical complement pathway through mechanisms involving FXIIIa.
- The study showed that fibrin clots do indeed activate the classical pathway, leading to complement activation, but factor H effectively downregulates this activation, highlighting the complex interplay between the complement and coagulation systems.
Article Synopsis
- The complement system plays a crucial role in the immune response to infections like SARS-CoV-2, with some evidence suggesting it can both harm (through cytokine storms) and protect against the virus.
- This study specifically looked at the roles of two complement proteins, C1q and C4b-binding protein (C4BP), in preventing SARS-CoV-2 infection, focusing on their ability to bind to the virus's spike protein.
- Results showed that C1q and C4BP not only reduced the virus's ability to enter cells but also decreased the expression of proinflammatory cytokines, suggesting they offer a protective effect during infection.
Article Synopsis
- The study examines how in utero adversities like hypoxia and malnutrition relate to the development of schizophrenia (SZ) by investigating specific proteins (l-ficolin and MASP-2) linked to the immune response in patients.
- Results show that SZ patients had significantly higher levels of l-ficolin (about 40% increase) and a notable gender difference in MASP-2 levels, especially among female patients.
- The study also notes that while there are increases in certain protein activities in SZ, there was no significant association with demographic factors like age, family history, or smoking habits.
Fusarium verticillioides NAT1 (FDB2) N-malonyltransferase is structurally, functionally and phylogenetically distinct from its N-acetyltransferase (NAT) homologues.
Eleni-Pavlina Karagianni Evanthia Kontomina Edward D Lowe Konstantinos Athanasopoulos Georgia Papanikolaou Robert B Sim Edith Sim
FEBS J
May 2023
Article Synopsis
- - Fusarium endophytes, particularly Fusarium verticillioides (or Gibberella moniliformis), damage cereal crops by detoxifying host defenses through a specific enzyme, (GIBMO)NAT1, which plays a crucial role in their pathogenicity and ability to produce mycotoxins.
- - The study presents the detailed crystallographic structure of (GIBMO)NAT1, highlighting its unique monomeric arrangement, which facilitates access to the catalytic core through two distinct "tunnel-like" openings.
- - Biochemical assays indicate varying substrate preferences among different NAT isoenzymes, suggesting they have evolved separately and that understanding (GIBMO)NAT1's structure and function
Article Synopsis
- * The study focused on properdin's role against Influenza A virus (IAV), demonstrating that it interacts with certain viral proteins and influences immune responses in a subtype-specific manner.
- * Properdin was shown to suppress H1N1 replication while promoting H3N2 replication, triggering different inflammatory responses in infected cells, thus highlighting its dual role during viral infections.
Article Synopsis
- - The complement system is a vital part of the immune system that helps fight off pathogens, operating through three main pathways: classical, alternative, and lectin.
- - It has various roles in combating viruses, including opsonization, inducing phagocytosis, and forming a membrane attack complex, while also enhancing immune responses.
- - However, many viruses have developed strategies to evade the complement system by producing inhibitors, which aids in their survival and makes them more prone to cause disease.
Article Synopsis
- C4b Binding Protein (C4BP) inhibits the complement system by binding to activated component C4b, working alongside factor I to prevent the formation of the C3-convertase, which is essential for immune response.
- The study investigates C4BP's ability to interact with Influenza A Virus (IAV) subtypes H1N1 and H3N2, discovering that C4BP binds to various viral proteins and affects infection rates differently for each subtype.
- C4BP decreases inflammatory responses for H1N1, acting as an entry inhibitor, while it enhances pro-inflammatory responses for H3N2, suggesting that C4BP has strain-dependent effects on IAV entry and replication independent of its
Article Synopsis
- - The complement system is a key part of the innate immune defense that identifies pathogens, with factor H serving to regulate complement activation on host cells and locally at infection sites like the lungs.
- - Factor H interacts with the influenza A virus (IAV), affecting its entry into cells and modulating the expression of matrix protein 1 (M1), with varying effects on inflammatory cytokines depending on the IAV subtype (H1N1 vs. H3N2).
- - Both factor H and a similar protein (VCP) demonstrate different impacts on luciferase reporter activity in response to H1N1 and H3N2, highlighting factor H's role in modulating IAV infection and inflammatory responses outside of
Article Synopsis
- The complement system plays a key role in the immune response against tumors, but many cancer cells, including those from Glioblastoma multiforme (GBM), can evade destruction by this system.
- Researchers identified that primary GBM cells secrete a protein called FHR5, which functions similarly to factor H in inhibiting immune attack.
- The study showed that GBM-derived FHR5 not only prevents complement-mediated cell lysis but also assists in the breakdown of the complement component C3b, helping tumor cells to survive immune surveillance.
Article Synopsis
- Enterococcus faecalis is a major cause of bloodstream infections in critically ill patients, and the complement system helps the immune response target these bacteria.
- In an experiment with mice, those treated with anti-Factor H antibodies showed a lower bacterial count in their blood and organs compared to controls, suggesting the treatment enhanced immune response.
- The study found that E faecalis can evade the alternative pathway of the complement system by binding Factor H to its surface, effectively escaping phagocytosis while still being targeted by other pathways.
Article Synopsis
- * A recombinant form of conglutinin (rfBC) was found to bind to and inhibit the growth of BCG (a model organism for studying tuberculosis) in a dose-dependent manner, as well as suppress the uptake of BCG by human macrophage cells (THP-1).
- * The study reveals that rfBC can inhibit mycobacterial uptake through two mechanisms: masking lipoarabinomannan to prevent receptor-mediated uptake and blocking interactions with iC3b,
Article Synopsis
- Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious conditions caused by factors like trauma or infection, leading to major inflammation and damage in lung tissues due to neutrophil activity.
- Researchers found that a recombinant chemotaxis inhibitory protein (rCHIPS) from Staphylococcus aureus can effectively reduce the severity of ALI/ARDS in mice by decreasing lung inflammation and permeability after exposure to harmful substances.
- Treatment with rCHIPS leads to reduced levels of inflammatory markers, less neutrophil and leukocyte recruitment, and improved lung health, indicating its potential as a therapeutic option for treating ALI/ARDS.
Article Synopsis
- Mycobacterium can enter macrophages, reduce complement activation, suppress macrophage death, and survive inside these immune cells.
- The study indicates that properdin and TSR4+5 inhibit the intake of BCG by macrophages and alter inflammatory responses, enhancing pro-inflammatory signals initially before decreasing over time.
- Findings highlight that properdin may play a role in preventing mycobacterial entry into macrophages, suggesting its potential importance in the immune response to tuberculosis.
Article Synopsis
- * The study identifies that human properdin binds to functionalized carbon nanotubes (CNTs) and enhances their uptake by immune cells, leading to increased inflammatory responses.
- * Coating carbon nanotubes with recombinant TSR4+5 serves as a method to reduce unwanted complement activation, indicating potential therapeutic applications for these modified nanoparticles in inflammatory conditions.
Article Synopsis
- The study aimed to evaluate the activities of MASP-1 and MASP-2 proteins in the blood of patients with ischaemic stroke and explore the relationship between certain genetic polymorphisms and the disease.
- A total of 250 patients and 300 healthy individuals were tested, revealing significantly higher MASP-1 and MASP-2 activities in stroke patients.
- The research identified two specific genetic variations (rs3203210 and rs147270785) that are linked to ischaemic stroke risk, suggesting that these genetic factors may serve as protective markers in the population studied.
Article Synopsis
- Nanomaterials, like carbon nanotubes (CNTs), need to be biocompatible and target-specific for therapeutic use, as the immune system tends to recognize them as foreign substances.* -
- Studies show that CNTs interact with immune cells, influencing their internal processing and overall immune response, particularly through interactions with the complement system.* -
- The modification of CNT surfaces affects complement activation, which can enhance or reduce inflammation and improve the effectiveness of these materials in therapeutic applications.*
Article Synopsis
- The complement system helps protect the host from infection and plays roles in tissue development and remodeling, with connections to the blood coagulation system.
- Genetic mutations and variations affecting complement components, like Factor H, contribute to autoimmune and inflammatory disorders, including systemic lupus erythematosus and rheumatoid arthritis.
- Factor H aids in self-tolerance through interactions that promote the clearance of apoptotic cells, which is important in maintaining immune balance and preventing inflammation.
Article Synopsis
- The three complement activation pathways—classic pathway (CP), alternative pathway, and lectin pathway (LP)—all lead to the key event of C3 activation through formation of C3 convertases.
- The C3 convertase complex requires both components C4 and C2, which are essential for CP and LP activation; without C4, CP cannot activate C3.
- In the absence of C4 and/or C2, the LP can still activate C3 through the action of mannan-binding lectin-associated serine protease-2, demonstrating a bypass route for C3 activation in certain physiological conditions.
Article Synopsis
- Carbon nanotubes (CNTs) are being researched for biomedical uses, particularly in drug delivery for diseases like tuberculosis, and their interaction with lung immune proteins is critical.
- The study investigates how surfactant protein D (SP-D) binds to CNTs, enhancing macrophage phagocytosis and spurring a pro-inflammatory response that may cause harm.
- The research suggests that while SP-D enhances CNTs' recognition and immune response, it also triggers pathways that can mitigate inflammation, highlighting the complex role of immune factors in developing effective CNT-based drug delivery systems.
Article Synopsis
- - Nanoparticles, particularly carbon nanotubes (CNTs), serve as promising tools for targeted drug delivery, but their interaction with the immune system poses challenges for effective treatment.
- - The study found that certain CNTs activate the complement system, enhancing their uptake by immune cells and altering the expression of inflammatory cytokines.
- - The research highlights how different nanoparticles interact with immune cells, indicating that the complement system can influence the immune response by recognizing specific molecular patterns on nanoparticles.
Article Synopsis
- Mycobacterium tuberculosis thrives inside macrophages, significantly impacting the body's response to the infection during latent tuberculosis.
- Factor H, a protein that regulates immune response, binds to M. bovis BCG and inhibits its uptake by macrophages in a dose-dependent manner, indicating that it might hinder infection.
- The presence of factor H alters the cytokine response during the early stages of infection, increasing pro-inflammatory cytokines like TNF-α while decreasing anti-inflammatory ones, thus influencing the survival of the bacteria.
Article Synopsis
- Properdin enhances the alternative complement pathway by stabilizing the C3 convertase complex through its polymeric forms made up of 53kDa monomers.
- The properdin monomers contain seven thrombospondin type I repeats (TSR 0-6) that share similarities with various proteins and complement components, indicating a complex evolutionary relationship.
- Research indicates that TSR4 and TSR5 together are necessary for effective C3b binding and stabilization of the C3 convertase, and when expressed together as a fusion protein, they can inhibit the alternative pathway of complement.
Article Synopsis
- Complement factor H has been studied for 50 years and is known for its role in the complement system, which helps regulate immune responses.
- It also acts as a binding protein for adrenomedullin, potentially protecting it from being broken down by enzymes.
- Adrenomedullin shows promise for treating vascular diseases, and factor H has been used alongside it in animal studies.
Article Synopsis
- The study investigates how carbon nanotubes (CNTs) interact with the complement system, which can affect their use in biomedical applications.
- It finds that pristine and modified CNTs primarily activate the complement via the classical pathway, enhancing their uptake by immune cells while reducing inflammation.
- Coating CNTs with C1q globular heads shows potential for controlling immune response and improving phagocytic clearance, highlighting the complexity of receptor interactions with CNTs.
Article Synopsis
- A European Union grant led by Prof. Mohamed R. Daha resulted in the development of a whole complement ELISA-based assay kit to screen for deficiencies in the complement system.
- The project produced a scientific publication and the commercially available WIESLAB(®) Complement system Screen kit, showcasing successful collaboration between researchers and a small-medium enterprise.
- The ongoing "Search for Applications for WIESLAB(®) Complement system Screen" project further explored the assay's use, supported by educational grants and royalties, and highlighted the lasting friendships formed among the research team.