The Effect Of Follicular Helper T Cells (TFH) On AID Regulation And Selection Of High Affinity Germinal Centre B Cells.
Funder
National Health and Medical Research Council
Funding Amount
$430,964.00
Summary
An integral component of an immune response to foreign pathogens is the production of antibodies by B cells. However, if antibodies react to self-antigens (human molecules rather than bacteria or viruses) they may also cause autoimmune diseases such as lupus. This research project is investigating the mechanisms that control antibody generation by B cells, and how these are dysregulated in autoimmune diseases, such as lupus.
Role Of Complement Factor H And Related Proteins In Regulating Complement Activation And Microbial Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage ....A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage and the regulatory proteins have therapeutic potential in this area. In addition many bacteria and other microorganisms, which should be destroyed by complement, escape by binding regulatory proteins. Understanding how this is achieved may reveal new targets for vaccine development. Knowledge of how the production of factor H and related proteins will help understand how inflammation occurs and how it might be controlled.Read moreRead less
Characterisation Of The SCR-domain Family Of Complement Regulators ; Structure, Function And Streptococcal Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
A group of proteins in blood called 'Complement' are activated in the presence of foreign cells or micro-organisms and this generally results in their destruction. It is important that this destructive activity is directed against foreign and not self tissue. This is achieved by a further family of proteins, including a protein called factor H, which switch off or regulate complement activity. How these proteins work is the principle focus of this project. There are many diseases in which damage ....A group of proteins in blood called 'Complement' are activated in the presence of foreign cells or micro-organisms and this generally results in their destruction. It is important that this destructive activity is directed against foreign and not self tissue. This is achieved by a further family of proteins, including a protein called factor H, which switch off or regulate complement activity. How these proteins work is the principle focus of this project. There are many diseases in which damage results from inadvertent complement activation and the regulatory proteins have therapeutic potential in this area. In addition, many bacteria and other micro-organisms, which should be destroyed by complement, escape by binding regulatory proteins. Understanding how this is achieved may assist in identifying targets for vaccine development.Read moreRead less
Structural And Functional Properties Of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Isoforms
Funder
National Health and Medical Research Council
Funding Amount
$188,623.00
Summary
Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1-CD31) is a member of the Ig-superfamily that is implicated in a variety of biological responses such as leukocyte transmigration, angiogenesis, cellular signaling, cell adhesion and migration. Recent studies from this laboratory has demonstrated that PECAM-1 contains intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM) that upon phosphorylation can mediate an inhibitory function through recruitment and activation of protei ....Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1-CD31) is a member of the Ig-superfamily that is implicated in a variety of biological responses such as leukocyte transmigration, angiogenesis, cellular signaling, cell adhesion and migration. Recent studies from this laboratory has demonstrated that PECAM-1 contains intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM) that upon phosphorylation can mediate an inhibitory function through recruitment and activation of protein tyrosine phosphatases, SHP-1 and SHP-2. We would therefore consider PECAM-1 as a new member of an emerging Ig-ITIM superfamily. Members of the Ig-ITIM gene family have both inhibitory-non-inhibitory receptors which upon ligation of specific receptors can globally stimulate or inhibit cellular activation in the context of B cells, Tcells, mast cells , endothelial cells or platelets. Balancing the threshold of cellular activation is critical in the immune response to tumours, pathogens or allergens, to arrest autoimmune and infectious disease, to provoke immunological memory from vaccination and to dampen the extent and duration of platelet activation. Our investigations are focussing on the isolation and functional characterisation of PECAM-1 family members to define their role in regulating cell signaling pathways in vascular and haematopoietic cells. We predict that PECAM-1 has numerous undefined family members that exist as multiple isoforms as a product of separate genes, alternative splicing of discrete exons and single point mutations giving rise to conservative and non-conversative amino acid changes. The longer term potential of this study is to provide knowledge for understanding the structural and functional roles of PECAM-1 isoforms in physiological cells in health and disease. This knowledge could then be applied to provide targets for novel therapeutic interventions in the clinical management of autoimmune disease, humoral and inflammatory responses.Read moreRead less