Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precurs ....Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precursors differentiate either along the male or the female pathway. Thus, this project aims to analyse in detail at which stage NEDD4 action is required and what are the crucial target proteins. This project could provide a deeper understanding of how post-translational modifications influence cell fate decisions during embryogenesis.Read moreRead less
Characterisation of plant cysteine proteases with therapeutic potential. This project aims to uncover how plant enzymes have effects on the immune system. This will allow the development of these enzymes as therapeutic agents for cancer and autoimmune conditions.
Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less
Understanding and exploiting bacterial sulfatases. Bacterial sulfatases participate in environmental nutrient cycling and are implicated in bacterial pathogenesis mechanisms. These enzymes catalyze the hydrolysis of sulfate esters and possess an unusual posttranslational active-site modification where a cysteine residue is oxidized to formylglycine. We will study the mechanism of these enzymes in detail and design inhibitors that exploit the reactivity of this aminoacid. This work has significan ....Understanding and exploiting bacterial sulfatases. Bacterial sulfatases participate in environmental nutrient cycling and are implicated in bacterial pathogenesis mechanisms. These enzymes catalyze the hydrolysis of sulfate esters and possess an unusual posttranslational active-site modification where a cysteine residue is oxidized to formylglycine. We will study the mechanism of these enzymes in detail and design inhibitors that exploit the reactivity of this aminoacid. This work has significance because of application to areas that include the treatment of cancer and bacterial infections. Additionally, we will clone novel carbohydrate sulfatases from the heparin-degrading bacterium Flavobacterium heparinum. These sulfatases will have use in biotechnology for characterization of sulfated glycoconjugates.Read moreRead less
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.
Structural and functional characterisation of compounds that inhibit the malarial aminopeptidases. Malaria is the world's most prevalent parasitic disease. Due to the rapid spread of drug resistant parasites there is a need to develop new antimalarial drugs. In this proposal we will characterise new targets and novel methods of inhibition that will form the basis of a new mechanism for antimalarial drugs.
Insect development : the role of cytochrome P450s. Pest insects vector human diseases such as malaria and impose a massive burden in agriculture due to control costs and production losses. The intelligent control of insect pests requires an understanding of their development that is controlled by hormones. This project will provide an in depth understanding of insect hormone synthesis/degradation that is controlled by a class of enzymes, the cytochrome P450s. This will increase the potential ....Insect development : the role of cytochrome P450s. Pest insects vector human diseases such as malaria and impose a massive burden in agriculture due to control costs and production losses. The intelligent control of insect pests requires an understanding of their development that is controlled by hormones. This project will provide an in depth understanding of insect hormone synthesis/degradation that is controlled by a class of enzymes, the cytochrome P450s. This will increase the potential for new insect-specific control strategies with a decreased environmental impact.Read moreRead less
Explaining the differences in affinity and of carbohydrate binding of the glycogen-sensing enzyme, AMP-protein activated kinase (AMPK). This project will provide fundamental molecular knowledge of how a complex enzyme, AMPK is controlled by the major sugar molecule, glycogen. Our research will increase our understanding of its role in metabolic diseases such as Type 2 diabetes and obesity.
To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be pl ....To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be placed on the disquieting reality whilst enjoy the use of antibiotics, an inescapable cost is the development of bacterial resistance. The increasing prevalence of bacterial tolerance against beta-lactams is a problem and as a result is a most pressing health issue. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560685
Funder
Australian Research Council
Funding Amount
$451,000.00
Summary
Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. Th ....Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. The bioelectrochemical imaging facility will be unique in Australia and establish an important cross-disciplinary approach within the international community.Read moreRead less