Investigating The Consequences Of Dysregulated Lipogenesis In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,647.00
Summary
Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to the investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.
Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, ....Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, for example in disease such as diabetes or transplant rejection. Furthermore, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
Molecular basis of antimicrobial and insecticidal activity of floral defensins from the Solonaceae. The flowers of Solanaceous plants produce high levels of defensins that protect the reproductive tissues against potential damage from microorganisms. The presence of related defensins in mammals, insects and plants indicates that they are part of an ancient defence mechanism. The floral defensins are potent antifungal molecules and surprisingly also have insecticidal activity. The aim of this pro ....Molecular basis of antimicrobial and insecticidal activity of floral defensins from the Solonaceae. The flowers of Solanaceous plants produce high levels of defensins that protect the reproductive tissues against potential damage from microorganisms. The presence of related defensins in mammals, insects and plants indicates that they are part of an ancient defence mechanism. The floral defensins are potent antifungal molecules and surprisingly also have insecticidal activity. The aim of this project is to understand the molecular basis of the antifungal and insecticide activity and to use this knowledge to produce improved molecules for crop protection.Read moreRead less
Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the ....Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the host's immune system will also be gained. The techniques established during the study of MSP-2 will be useful for the study of larger proteins and protein complexes from many systems in the future.Read moreRead less
Searching for novel protein domains: A bioinformatic analysis of whole proteomes. The functional annotation of the set of proteins encoded by a whole genome (the "proteome") is a crucial component of genome research. The aim of this project is to extend the functional and structural annotation of large protein databases by identifying novel protein domain families and building a novel domain library. Our approach is semi-automated and fast, thanks to execution in the fastest parallel supercom ....Searching for novel protein domains: A bioinformatic analysis of whole proteomes. The functional annotation of the set of proteins encoded by a whole genome (the "proteome") is a crucial component of genome research. The aim of this project is to extend the functional and structural annotation of large protein databases by identifying novel protein domain families and building a novel domain library. Our approach is semi-automated and fast, thanks to execution in the fastest parallel supercomputer in Australia available at the Victorian Partnership for Advanced Computing. Our preliminary data demonstrates that our method is feasible.Read moreRead less
Autophagy and the nucleus. Autophagy is a degradation pathway that is essential for survival, internal change (differentiation and development) and maintenance of physiological equilibrium (homeostasis). Moreover autophagy serves to protect higher organisms against infections, cancer and neurodegeneration. This project seeks to better understand the mechanisim by which parts of the nucleus can be degraded by autophagy and how this relates to diseases which may involve defects in, or abnormal deg ....Autophagy and the nucleus. Autophagy is a degradation pathway that is essential for survival, internal change (differentiation and development) and maintenance of physiological equilibrium (homeostasis). Moreover autophagy serves to protect higher organisms against infections, cancer and neurodegeneration. This project seeks to better understand the mechanisim by which parts of the nucleus can be degraded by autophagy and how this relates to diseases which may involve defects in, or abnormal degradation of nuclear components. Benefit will accrue from a contribution to knowledge with future potential to impact on disease, as well as strengthening links with the international network working in the field of autophagy.Read moreRead less
Development of high-throughput in silico methods for protein structure determination by X-ray crystallography. This work will have major outcomes for structural biology research at a national and international level. The ability to perform MR calculations using an exhaustive set of search models will offer a timesaving of weeks to months in a typical successful structure determination. Further, significant insights will be gained into the use of high-performance GRID computing in protein struct ....Development of high-throughput in silico methods for protein structure determination by X-ray crystallography. This work will have major outcomes for structural biology research at a national and international level. The ability to perform MR calculations using an exhaustive set of search models will offer a timesaving of weeks to months in a typical successful structure determination. Further, significant insights will be gained into the use of high-performance GRID computing in protein structure determination by X-ray crystallography. This knowledge has considerable impact on our ability to undertake high quality structural biology research - a key area in the majority of biological research programmes. Read moreRead less
Structural and Functional studies on Membrane Attack Complex / Perforin-like proteins. Membrane Attack Complex Perforin (MACPF) proteins play crucial roles in immunity and development. Together, these molecules comprise the largest family of pore forming proteins in eukaryotes. This proposal will result in a major advancement of knowledge in our understanding of the MACPF mechanism of pore formation. These data will provide fundamental insight into how proteins can change shape and adopt both wa ....Structural and Functional studies on Membrane Attack Complex / Perforin-like proteins. Membrane Attack Complex Perforin (MACPF) proteins play crucial roles in immunity and development. Together, these molecules comprise the largest family of pore forming proteins in eukaryotes. This proposal will result in a major advancement of knowledge in our understanding of the MACPF mechanism of pore formation. These data will provide fundamental insight into how proteins can change shape and adopt both water-soluble and membrane bound states. Our work will also eventually be important in developing approaches to control unwanted MACPF function, for example in diabetes or transplant rejection. Finally, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. ....Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. Understanding fat breakdown is also important for developing new processing technologies in the food industry.Read moreRead less