Walter and Eliza Hall Institute of Medical Research

About: Walter and Eliza Hall Institute of Medical Research is a nonprofit organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Antigen & Immune system. The organization has 5012 authors who have published 10620 publications receiving 873561 citations.

Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs.

Abstract: Apoptosis is a physiological cell death process important for development, homeostasis and the immune defence of multicellular animals. The key effectors of apoptosis are caspases, cysteine proteases that cleave after aspartate residues. The inhibitor of apoptosis (IAP) family of proteins prevent cell death by binding to and inhibiting active caspases and are negatively regulated by IAP-binding proteins, such as the mammalian protein DIABLO/Smac. IAPs are characterized by the presence of one to three domains known as baculoviral IAP repeat (BIR) domains and many also have a RING-finger domain at their carboxyl terminus. More recently, a second group of BIR-domain-containing proteins (BIRPs) have been identified that includes the mammalian proteins Bruce and Survivin as well as BIR-containing proteins in yeasts and Caenorhabditis elegans. These Survivin-like BIRPs regulate cytokinesis and mitotic spindle formation. In this review, we describe the IAPs and other BIRPs, their evolutionary relationships and their subcellular and tissue localizations.

Apoptosis in the development and treatment of cancer

Abstract: Our somatic cells are born by mitosis and almost all will die by apoptosis, a physiological process of cellular suicide. Cancers can occur when this balance is disturbed, either by an increase in cell proliferation or a decrease in cell death. The goal of cancer therapy is to promote the death of cancer cells without causing too much damage to normal cells. Our knowledge of the mechanisms of apoptosis has enhanced our understanding of how some cancers originate and progress. It has also revealed that existing cancer therapies can work in two ways, by induction of apoptosis as well as by direct toxicity. In some cases resistance to apoptosis may explain why cancer therapies fail. Novel treatments designed to exploit our knowledge of apoptotic mechanisms are under development to promote apoptosis of cancer cells and limit concurrent death of normal cells.

BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death.

Abstract: The BH3-only members of the Bcl-2 protein family are essential initiators of programmed cell death and are required for apoptosis induced by cytotoxic stimuli. These proteins have evolved to recognise distinct forms of cell stress. In response, they unleash the apoptotic cascade by inactivating the protective function of the pro-survival members of the Bcl-2 family and by activating the Bax/Bax-like pro-apoptotic family members.

High affinity germinal center B cells are actively selected into the plasma cell compartment

Abstract: A hallmark of T cell–dependent immune responses is the progressive increase in the ability of serum antibodies to bind antigen and provide immune protection. Affinity maturation of the antibody response is thought to be connected with the preferential survival of germinal centre (GC) B cells that have acquired increased affinity for antigen via somatic hypermutation of their immunoglobulin genes. However, the mechanisms that drive affinity maturation remain obscure because of the difficulty in tracking the affinity-based selection of GC B cells and their differentiation into plasma cells. We describe a powerful new model that allows these processes to be followed as they occur in vivo. In contrast to evidence from in vitro systems, responding GC B cells do not undergo plasma cell differentiation stochastically. Rather, only GC B cells that have acquired high affinity for the immunizing antigen form plasma cells. Affinity maturation is therefore driven by a tightly controlled mechanism that ensures only antibodies with the greatest possibility of neutralizing foreign antigen are produced. Because the body can sustain only limited numbers of plasma cells, this “quality control” over plasma cell differentiation is likely critical for establishing effective humoral immunity.