CIDB: Chlamydia Interactive Database for cross-querying genomics, transcriptomics and proteomics data

Chlamydiae are important pathogens of humans, birds and a wide range of animals. They are a unique group of bacteria, characterized by their developmental cycle. Chlamydia has been difficult to study because of their obligate intracellular growth habit and lack of a genetic transformation system. However, the past 5 years has seen the full genome sequencing of seven strains of Chlamydia and a rapid expansion of genomic, transcriptomic (RT-PCR, microarray) and proteomic analysis of these pathogens. The Chlamydia Interactive Database (CIDB) described here is the first database of its type that holds genomic, RT-PCR, microarray and proteomics data sets that can be cross-queried by researchers for patterns in the data. Combining the data of many research groups into a single database and cross-querying from different perspectives should enhance our understanding of the complex cell biology of these pathogens. The database is available at: http://www3.it.deakin.edu.au:8080/CIDB/.

Focusing in on structural genomics : the University of Queensland structural biology pipeline

The flood of new genomic sequence information together with technological innovations in protein structure determination have led to worldwide structural genomics (SG) initiatives. The goals of SG initiatives are to accelerate the process of protein structure determination, to fill in protein fold space and to provide information about the function of uncharacterized proteins. In the long-term, these outcomes are likely to impact on medical biotechnology and drug discovery, leading to a better understanding of disease as well as the development of new therapeutics. Here we describe the high throughput pipeline established at the University of Queensland in Australia. In this focused pipeline, the targets for structure determination are proteins that are expressed in mouse macrophage cells and that are inferred to have a role in innate immunity. The aim is to characterize the molecular structure and the biochemical and cellular function of these targets by using a parallel processing pipeline. The pipeline is designed to work with tens to hundreds of target gene products and comprises target selection, cloning, expression, purification, crystallization and structure determination. The structures from this pipeline will provide insights into the function of previously uncharacterized macrophage proteins and could lead to the validation of new drug targets for chronic obstructive pulmonary disease and arthritis.

Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites

Techniques for targeted genetic disruption in Plasmodium, the causative agent of malaria, are currently intractable for those genes that are essential for blood stage development. The ability to use RNA interference (RNAi) to silence gene expression
would provide a powerful means to gain valuable insight into the pathogenic blood stages but its functionality in Plasmodium remains controversial. Here we have used various RNA-based gene silencing approaches to test the utility of RNAi in malaria
parasites and have undertaken an extensive comparative genomics search using profile hidden Markov models to clarify whether RNAi machinery
exists in malaria. These investigative approaches revealed that Plasmodium lacks the enzymology required for RNAi-based ablation of gene expression
and indeed no experimental evidence for RNAi was observed. In its absence, the most likely explanations for previously reported RNAi-mediated knockdown are either the general toxicity of introduced RNA (with global down-regulation of gene expression) or a specific antisense effect mechanistically distinct from RNAi, which will need systematic
analysis if it is to be of use as a molecular genetic tool for malaria parasites.

Comparative genomics and transcriptomics of lactation

Lactation is an important characteristic of mammalian reproduction sometimes referred to as the quintessence of mammals. Comparative genomics and transcriptomics experiments are allowing a more in-depth molecular analysis of the evolution of lactation throughout the mammalian kingdom and these recent results are reviewed here. Milk cell and mammary gland gene expression analysis with sequencing methodology have started to reveal conserved or specific milk protein and components of the lactation system of monotreme, marsupial and eutherian lineages. These experiments have confirmed the ancient origin of the complex lactation system and provided useful insight into the function of specific milk proteins in the control of the lactation programme or the role of milk in the regulation of growth and development of the young beyond simple nutritive aspects.

A survey of cloud-based service computing solutions for mammalian genomics

Cloud-based service computing has started to change the way how research in science, in particular biology, medicine, and engineering, is being carried out. Researchers in the area of mammalian genomics have taken advantage of cloud computing technology to cost-effectively process large amounts of data and speed up discovery. Mammalian genomics is limited by the cost and complexity of analysis, which require large amounts of computational resources to analyse huge amount of data and biology specialists to interpret results. On the other hand the application of this technology requires computing knowledge, in particular programming and operations management skills to develop high performance computing (HPC) applications and deploy them on HPC clouds. We carried out a survey of cloud-based service computing solutions, as the most recent and promising instantiations of distributed computing systems, in the context their use in research of mammalian genomic analysis. We describe our most recent research and development effort which focuses on building Software as a Service (SaaS) clouds to simplify the use of HPC clouds for carrying out mammalian genomic analysis.

Bioactive functions of milk proteins: a comparative genomics approach

The composition of milk includes factors required to provide appropriate nutrition for the growth of the neonate. However, it is now clear that milk has many functions and comprises bioactive molecules that play a central role in regulating developmental processes in the young while providing a protective function for both the suckled young and the mammary gland during the lactation cycle. Identifying these bioactives and their physiological function in eutherians can be difficult and requires extensive screening of milk components that may function to improve well-being and options for prevention and treatment of disease. New animal models with unique reproductive strategies are now becoming increasingly relevant to search for these factors.

Genomics based biomarker discovery in oral squamous cell carcinoma

 The present thesis showed signaling mechanisms and pathways essential for oral cancer progression through genomics approach. It has identified markers that are of diagnostic, prognostic and therapeutic importance. It has also shown that aspirin is a potential drug in oral cancer treatment.

"Cancer 2015": a prospective, population-based cancer cohort-phase 1: feasibility of genomics-guided precision medicine in the clinic

"Cancer 2015" is a longitudinal and prospective cohort. It is a phased study whose aim was to pilot recruiting 1000 patients during phase 1 to establish the feasibility of providing a population-based genomics cohort. Newly diagnosed adult patients with solid cancers, with residual tumour material for molecular genomics testing, were recruited into the cohort for the collection of a dataset containing clinical, molecular pathology, health resource use and outcomes data. 1685 patients have been recruited over almost 3 years from five hospitals. Thirty-two percent are aged between 61-70 years old, with a median age of 63 years. Diagnostic tumour samples were obtained for 90% of these patients for multiple parallel sequencing. Patients identified with somatic mutations of potentially "actionable" variants represented almost 10% of those tumours sequenced, while 42% of the cohort had no mutations identified. These genomic data were annotated with information such as cancer site, stage, morphology, treatment and patient outcomes and health resource use and cost. This cohort has delivered its main objective of establishing an upscalable genomics cohort within a clinical setting and in phase 2 aims to develop a protocol for how genomics testing can be used in real-time clinical decision-making, providing evidence on the value of precision medicine to clinical practice.

Contrasting patterns of population connectivity between regions in a commercially important mollusc Haliotis rubra: integrating population genetics, genomics and marine LiDAR data

Estimating contemporary genetic structure and population connectivity in marine species is challenging, often compromised by genetic markers that lack adequate sensitivity, and unstructured sampling regimes. We show how these limitations can be overcome via the integration of modern genotyping methods and sampling designs guided by LIDAR and SONAR datasets. Here we explore patterns of gene flow and local genetic structure in a commercially harvested abalone species (Haliotis rubra) from South Eastern Australia, where the viability of fishing stocks is believed to be dictated by recruitment from local sources. Using a panel of microsatellite and genome-wide SNP markers we compare allele frequencies across a replicated hierarchical sampling area guided by bathymetric LIDAR imagery. Results indicate high levels of gene flow and no significant genetic structure within or between benthic reef habitats across 1400 km of coastline. These findings differ to those reported for other regions of the fishery indicating that larval supply is likely to be spatially variable, with implications for management and long-term recovery from stock depletion. The study highlights the utility of suitably designed genetic markers and spatially informed sampling strategies for gaining insights into recruitment patterns in benthic marine species, assisting in conservation planning and sustainable management of fisheries.

What are we missing about marine invasions? Filling in the gaps with evolutionary genomics

Research on invasion biology has been largely dominated by studies on the ecological effects of invasion events, although recently, evolutionary processes have been shown to be important to invasion success. This is largely attributed to novel genomic tools that provide new opportunities to unravel the natural history, taxonomy, and invasion pathways of invasive species, as well as the genetic basis of adaptive traits that allow them to expand within and beyond their native range. Despite these advances and the growing literature of genomic research on terrestrial pests, these tools have not been widely applied to marine invasive species. This is in part due to the perception that high levels of dispersal and connectivity in many invasive marine species can limit the opportunity for local adaptation. However, there is growing evidence that even in species with high dispersal potential, significant site-specific adaptation can occur. We review how these “omic” tools provide unprecedented opportunities to characterise the role of adaptive variation, physiological tolerance, and epigenetic processes in determining the success of marine invaders. Yet, rapid range expansion in invasions can confound the analysis of genomic data, so we also review how data should be properly analysed and carefully interpreted under such circumstances. Although there are a limited number of studies pioneering this research in marine systems, this review highlights how future studies can be designed to integrate ecological and evolutionary information. Such datasets will be imperative for the effective management of marine pests.

Heterologous microarray experiments used to identify the early gene response to heat stress in a coral reef fish

Coral reef fishes are expected to experience rising sea surface temperatures due to climate change. How well tropical reef fishes will respond to these increased temperatures and which genes are important in the response to elevated temperatures is not known. Microarray technology provides a powerful tool for gene discovery studies, but the development of microarrays for individual species can be expensive and time-consuming. In this study, we tested the suitability of a Danio rerio oligonucleotide microarray for application in a species with few genomic resources, the coral reef fish Pomacentrus moluccensis. Results from a comparative genomic hybridization experiment and direct sequence comparisons indicate that for most genes there is considerable sequence similarity between the two species, suggesting that the D. rerio array is useful for genomic studies of P. moluccensis. We employed this heterologous microarray approach to characterize the early transcriptional response to heat stress in P. moluccensis. A total of 111 gene loci, many of which are involved in protein processing, transcription, and cell growth, showed significant changes in transcript abundance following exposure to elevated temperatures. Changes in transcript abundance were validated for a selection of candidate genes using quantitative real-time polymerase chain reaction. This study demonstrates that heterologous microarrays can be successfully employed to study species for which specific microarrays have not yet been developed, and so have the potential to greatly enhance the utility of microarray technology to the field of environmental and functional genomics.