Gerondakis S.,Burnet Institute
Cold Spring Harbor perspectives in biology | Year: 2010
This article focuses on the functions of NF-kappaB that vitally impact lymphocytes and thus adaptive immunity. NF-kappaB has long been known to be essential for many of the responses of mature lymphocytes to invading pathogens. In addition, NF-kappaB has important functions in shaping the immune system so it is able to generate adaptive responses to pathogens. In both contexts, NF-kappaB executes critical cell-autonomous functions within lymphocytes as well as within supportive cells, such as antigen-presenting cells or epithelial cells. It is these aspects of NF-kappaB's physiologic impact that we address in this article. Source
Chan J.A.,Burnet Institute
Cellular and molecular life sciences : CMLS | Year: 2014
Understanding the targets and mechanisms of human immunity to malaria caused by Plasmodium falciparum is crucial for advancing effective vaccines and developing tools for measuring immunity and exposure in populations. Acquired immunity to malaria predominantly targets the blood stage of infection when merozoites of Plasmodium spp. infect erythrocytes and replicate within them. During the intra-erythrocytic development of P. falciparum, numerous parasite-derived antigens are expressed on the surface of infected erythrocytes (IEs). These antigens enable P. falciparum-IEs to adhere in the vasculature and accumulate in multiple organs, which is a key process in the pathogenesis of disease. IE surface antigens, often referred to as variant surface antigens, are important targets of acquired protective immunity and include PfEMP1, RIFIN, STEVOR and SURFIN. These antigens are highly polymorphic and encoded by multigene families, which generate substantial antigenic diversity to mediate immune evasion. The most important immune target appears to be PfEMP1, which is a major ligand for vascular adhesion and sequestration of IEs. Studies are beginning to identify specific variants of PfEMP1 linked to disease pathogenesis that may be suitable for vaccine development, but overcoming antigenic diversity in PfEMP1 remains a major challenge. Much less is known about other surface antigens, or antigens on the surface of gametocyte-IEs, the effector mechanisms that mediate immunity, and how immunity is acquired and maintained over time; these are important topics for future research. Source
Gold J.,Burnet Institute
Journal of medical Internet research | Year: 2012
Online social networking sites offer a novel setting for the delivery of health promotion interventions due to their potential to reach a large population and the possibility for two-way engagement. However, few have attempted to host interventions on these sites, or to use the range of interactive functions available to enhance the delivery of health-related messages. This paper presents lessons learnt from "The FaceSpace Project", a sexual health promotion intervention using social networking sites targeting two key at-risk groups. Based on our experience, we make recommendations for developing and implementing health promotion interventions on these sites. Elements crucial for developing interventions include establishing a multidisciplinary team, allowing adequate time for obtaining approvals, securing sufficient resources for building and maintaining an online presence, and developing an integrated process and impact evaluation framework. With two-way interaction an important and novel feature of health promotion interventions in this medium, we also present strategies trialled to generate interest and engagement in our intervention. Social networking sites are now an established part of the online environment; our experience in developing and implementing a health promotion intervention using this medium are of direct relevance and utility for all health organizations creating a presence in this new environment. Source
Burnet Institute | Date: 2011-06-01
A method for quantifying apoptosis in absolute terms in a cellular sample by real-time ligation-mediated PCR, the method comprising: (a) obtaining first control genomic nucleic acid which is apoptotic nucleic acid from a cellular sample that is substantially 100% apoptotic; (b) obtaining test genomic nucleic acid derived from a test cellular sample; (c) subjecting a plurality of different known concentrations of first control genomic nucleic acid to real-time apoptosis-specific multi-product PCR in the presence of a nucleic acid-binding fluorophore or other detectable tag to obtain a threshold cycle number (Ct) or other equivalent value at different nucleic acid concentrations and establishing a linear numerical relationship between Ct or equivalent value and apoptotic nucleic acid concentration; (d) subjecting test nucleic acid to real-time apoptosis-specific multi-product PCR in the presence of a nucleic acid-binding fluorophore or other detectable tag to obtain a Ct or other equivalent value; and (e) establishing the quantity of apoptotic nucleic acid in the test nucleic acid, which corresponds numerically to the concentration of nucleic acid in (c) which determines the Ct or equivalent value obtained in (d). A standard composition of isolated genomic nucleic acid comprising substantially 100% apoptotic nucleic acid or comprising apoptotic nucleic acid as a predetermined proportion of an isolated nucleic acid sample. A kit comprising same.
Burnet Institute | Date: 2010-06-22
The invention relates to chimeric proteins comprising an antigen and a trimer forming portion or a trimer and virus-like particle forming portion of foamy virus envelope protein (FV TM). The trimer or trimer and virus-like particle forming portion comprises i) full length foamy virus transmembrane protein; ii) foamy virus transmembrane protein absent a functional cytoplasmic domain; iii) foamy virus transmembrane protein absent a functional cytoplasmic domain and transmembrane domain; iv) foamy virus ectodomain comprising N-terminal heptad repeat region and cysteine rich region between N-terminal heptad repeat region and C-terminal -helical region; v) N-terminal heptad repeat region; vi) a functional variant of any one of i) to v); or vii) any one of i) to vi) lacking an FV fusion peptide domain. In particular, the antigen is an antigen of a virus envelope protein, such as HIV gp 120. Soluble and membrane bound forms of trimeric and higher oligomeric forms of the chimeric proteins are provided as well as nucleic acid molecules encoding and expressing same, viral-like particles comprising same, compositions including pharmaceutical compositions, host cells and kits. Methods are described for producing immune responses including antibodies determined by the chimeric protein or VLP, as well as methods of screening using the chimeric protein, VLP and/or antibodies.