A Saturation Screen For Modifiers Of Epigenetic Reprogramming In The Mouse: Phase II
Funder
National Health and Medical Research Council
Funding Amount
$1,374,820.00
Summary
The building of a complex organism, such as a human embryo, is a self-directed process driven by the genetic information inherited from the parents. As the cells differentiate into a diverse array of tissues, the genetic information does not change. What does change is the epigenetic state of the genome in each cell type. We still understand little about this epigenetic reprogramming except that mistakes in the process lead to death and disease. Our work aims to address this lack of knowledge
Use Of Peptides From Phage Display Libraries To Probe The Function Of AMA-1 And Other Malaria Surface Proteins
Funder
National Health and Medical Research Council
Funding Amount
$316,650.00
Summary
Malaria remains a major cause of mortality and morbidity worldwide. Much current research is aimed at exploring the molecular interactions between malarial proteins and host components in order to gain a deeper understanding of parasite virulence mechanisms, design alternative anti-malarial approaches and improve vaccine design. The apical membrane antigen-1( AMA-1) is a surface exposed protein which is thought to play a crucial role in invasion of red blood cells by malaria parasites, and is cu ....Malaria remains a major cause of mortality and morbidity worldwide. Much current research is aimed at exploring the molecular interactions between malarial proteins and host components in order to gain a deeper understanding of parasite virulence mechanisms, design alternative anti-malarial approaches and improve vaccine design. The apical membrane antigen-1( AMA-1) is a surface exposed protein which is thought to play a crucial role in invasion of red blood cells by malaria parasites, and is currently one of the leading asexual stage vaccine candidates. While antibodies to AMA-1 prevents malaria invasion, little is known about the role of the antigen in the invasion process. The aim of this proposal is to investigate the molecular interactions that makes AMA-1 an important player in the invasion process. We propose to map the regions of AMA-1 responsible for binding a set of peptides which we have isolated from random peptide libraries. Since these peptides inhibit the invasion of parasites into red blood cells, regions of AMA1- that bind these peptides will be of functional significance. A further outcome will be the identification of peptide residues essential for the inhibition of invasion followed by in vitro evolution of these peptides to improve their binding and inhibitory properties. A molecular description of how AMA1 binding peptides prevent parasite invasion of host erythrocytes will improve our understanding of the invasion process, and aid in improving vaccines based on AMA-1. Furthermore, this peptide-AMA-1 interaction will be assessed as a possible target for the development of novel anti-malarial therapies. Using random peptide libraries we have selected peptides that specifically bind to other merozoite surface proteins thought to be involved in merozoite invasion of erythrocytes. The ability of these peptides to inhibit merozoite invasion will be examined and characterised as described above.Read moreRead less
I am a developmental biologist using genetic approaches in the model vertebrate, zebrafish, to study the molecular basis for muscle formation. My laboratory studies the basic biology of muscle and applies that knowledge to create accurate disease models o
Studies Of Myeloid Leukaemogenesis In The Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$171,827.00
Summary
This project aims to investigate the causes of white blood cell cancer, or leukaemia, at the molecular level, using a novel approach in zebrafish. Zebrafish provide a powerful experimental model for developmental genetics, largely due to the visual and technical accessibility of embryos for experimentation. We plan to introduce a fluorescent molecular tag into the white blood cells in order to directly visualise them. We will then predispose these fish to leukaemia and screen for mutants with en ....This project aims to investigate the causes of white blood cell cancer, or leukaemia, at the molecular level, using a novel approach in zebrafish. Zebrafish provide a powerful experimental model for developmental genetics, largely due to the visual and technical accessibility of embryos for experimentation. We plan to introduce a fluorescent molecular tag into the white blood cells in order to directly visualise them. We will then predispose these fish to leukaemia and screen for mutants with enhanced or suppressed leukaemia. We anticipate that the mutants will allow new genes involved in the development of leukaemia to be identified.Read moreRead less