Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great pot ....Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.Read moreRead less
Convergent Evolution of Desert Lizards: Phylogenomic and Morphological Analyses of Limb Development. Evolutionary convergence, where similar traits evolve independently in multiple lineages, is a fundamental biological process, which affects many aspects of an organism's morphology. Despite its importance we don't understand what underlies the convergence we observe in nature - does convergence in genetic make-up underlie convergence in morphology? We will investigate whether similar hindlimb mo ....Convergent Evolution of Desert Lizards: Phylogenomic and Morphological Analyses of Limb Development. Evolutionary convergence, where similar traits evolve independently in multiple lineages, is a fundamental biological process, which affects many aspects of an organism's morphology. Despite its importance we don't understand what underlies the convergence we observe in nature - does convergence in genetic make-up underlie convergence in morphology? We will investigate whether similar hindlimb morphologies are determined by the same genetic mechanisms in iguanian lizards of Australia and North America. Our study will be the first of its kind in vertebrates and will provide significant information about the evolutionary link between an animal's morphology and its genetic make-up.Read moreRead less
Assessing Acellular Pertussis Vaccine Effectiveness: Integrating Transmission Models, Genetics And Cohort Data To Inform Policy
Funder
National Health and Medical Research Council
Funding Amount
$429,597.00
Summary
Between 2009-12 a very large epidemic of whooping cough occurred in Australia. More surprisingly during the course of the epidemic the bacteria that cause whooping cough showed genetic changes that seemed to avoid protection provided by the current vaccine against whooping cough in Australia. This grant seeks to use mathematical models of whooping cough transmission to explain how this occurred and to establish whether alternative vaccination strategies might improve the control of this disease.
Enhancing Control Of Enteric Bacteria Through Pathogen Genomics
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Bacteria part of the Enterobacteriaceae family are responsible for causing significant enteric disease in Australia and internationally. Compounding the public health threat posed by these enteric bacteria is the rise in antimicrobial resistance, which limits treatment options. This project has three complementary research objectives; 1) to investigate new control strategies; 2) to better understand outbreak dynamics and; 3) to explore how bacteria are causing new disease in humans.
Reducing Pertussis Burden By Optimising Molecular Epidemiological Surveillance Of Epidemic Bordetella Pertussis In Australia
Funder
National Health and Medical Research Council
Funding Amount
$487,258.00
Summary
Australia has experienced a prolonged epidemic of pertussis from 2008 to 2012 and is currently experiencing another epidemic. In this project, we aim to elucidate the evolutionary dynamics of the epidemics by genome sequencing and develop a practical high throughput culture independent method for epidemiological typing. The outcomes will be highly significant for surveillance of pertussis infections and designing strategies for control and prevention of pertussis.
Origins And Relationships Of Shigella And Enteroinvasive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$377,310.00
Summary
Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoe ....Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoea in less developed countries and has also caused large outbreaks in developed countries. It is now clear that Shigella and E. coli are really one species. EIEC and Shigella strains are variants of E. coli with humans as the only host. However separation of the two in all records and most studies means that there is no integrated understanding of the forms. We aim to study the relationships of Shigella and EIEC and expect significant insights into the origins of Shigella-EIEC. This will facilitate diagnosis and understanding of the disease(s) and lead to a far better classification . EIEC-Shigella strains have arisen from other E. coli independently. This has happened seven times in the derivation of Shigella and we expect more such events with EIEC. An interesting phenomenon during this process is that strains tend to lose metabolic functions. In this study we will look at what, why and how functions are lost. O antigens are important in evading the host immune system. Shigella strains obtained many O antigens, the majority apparently from other species. This is quite likely the key to its success. We will look at how Shigella obtained new O antigens. This project will be significant in the understanding of Shigell-EIEC, a very significant human pathogen, and in general for understanding emergence of new pathogens.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Black Death Genomics And The Evolution Of Pathogen Virulence
Funder
National Health and Medical Research Council
Funding Amount
$525,412.00
Summary
The Black Death was one of the most lethal plagues of antiquity and changed the course of human history. We will reconstruct and analyse the evolution of its causative agent – the bacterium Yersinia pestis – sampled from human skeletal remains dating back to the Black Death and beyond. We will determine the mutations that changed the virulence of plague epidemics through time, enabling a unique insight into the most dramatic example of pathogen emergence that has ever been available for study.