BACTERIAL PATHOGENESIS, BIOFILMS AND ANTIBIOTIC RESISTANCE

Antibiotics commonly target Antibiotics commonly target and disrupt the metabolism of individual bacteria, with drug resistance arising via mutation of their metabolic pathways, acquisition of antibiotic resistance genes through horizontal gene transfer, or growth as complex biofilm communities. IBID scientists are elucidating and targeting critical events in control of bacterial growth, the molecular mechanisms which sustain bacterial biofilms or are involved in bacterial interactions with host cells and tissues. These studies will allow us to discover new targets for the development of antibiotics that target novel pathways of bacterial cell division, replication, biofilm development or host-pathogen interactions. We will focus this work on the biggest threats in terms of drug resistance i.e. Staphylococcus aureus and Pseudomonas aeruginosa.

DISCOVERING NEW INTERVENTIONS IN IMMUNO-REGULATORY PATHWAYS TO CONTROL INFECTIOUS AND NON-INFECTIOUS INFLAMMATORY DISEASES.

Pathogens have the ability to control various facets of immunological networks. Parasites, for example, can influence the balance between anti- and pro-inflammatory responses (immunosuppression and immunotolerance) not only in their host, but in 'bystander' pathogens as well. Similarly, many viruses subvert the immune response to their own benefit. IBID's work in this area will allow us to identify new entry points into the immune system networks that could be controlled by drug intervention, and utilise successful viral strategies as models for developing new anti-inflammatory agents. Since different pathogens influence different immunological pathways IBID resources place us in a unique position to exploit this area of research. We expect to find applications to other major human immune disorders such as asthma and arthritis.

HIGH-THROUGHPUT SCREENING OF CHEMICAL LIBRARIES FOR ANTI-PARASITE DRUG TARGETS.

Our research has driven us to develop specialised recombinant DNA techniques for expressing parasite drug targets. Development of simple micro-array drug-screening assays has opened the possibility to use these targets as screens in High-Throughput Chemical Libraries to identify new lead drug compounds. We have already won international funding for a drug screening program to identify new lead compounds that target aminopeptidases of the malaria parasites. We will be applying the same screening approach to identify new antibiotics that block bacterial cell division or biofilm formation.

GASTRO-INTESTINAL INFECTIONS.

Collaborative research between UTS and St. Vincents Hospital has discovered that the gut flora is more complex than previously believed. Development of molecular techniques combined with microscopy revealed that the gut is inhabited by a multitude of organisms, both bacterial and parasitic, that are potentially infectious and likely to contribute to a range of intestinal disorders such as ulcers and irritable bowel syndrome. This research has already received attention by highly respected medical journals and by the media. IBID has a unique capacity to investigate the interactions between these organisms in their in vivo environment, their epidemiology and causation of common intestinal diseases and their impact on the mucosal immunity. Furthermore, we will also develop new microscopic and molecular diagnostic procedures to screen and monitor for the presence of infectious gut flora.

MOLECULAR  BIOLOGY  BIOINFORMATICS AND COMPARATIVE GENOMICS.

Researchers in IBID have used molecular biological methods to discover and produce vaccines for various animal and human diseases (neosporosis, fasciolosis and coccidiocis. In recent times, the enormous and rapidly growing genomic information in the public databases has dramatically altered how we study infectious diseases. Bioinformatics is the use of mathematical and data mining tools to identify and understand the biological function of families of genes and proteins. Bioinformatics also provides tools for interrogating and interpreting this information to discover fundamental processes in bacterial and parasite biology, not only at the molecule level but also at the whole organism and community level. Combined with the nexus of IBID researchers we employ bioinformatics in the discovery of molecules important for infectious disease (and hence vaccine and drug targets), elucidate networks and processes involved in cell division, cell growth and drug resistance and investigate the genomes of newly discovered infectious gut flora.