The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Unfortunately the immune system can sometimes lose specificity and attack the host resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. By understanding these complex processes the team aims to harness the unique therapeutic pro ....The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Unfortunately the immune system can sometimes lose specificity and attack the host resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. By understanding these complex processes the team aims to harness the unique therapeutic properties of our own immune system and translate their findings into the clinic.Read moreRead less
Host Parasite Interactions: Disease, Pathogenesis And Control
Funder
National Health and Medical Research Council
Funding Amount
$13,738,897.00
Summary
Our program will investigate two major global parasitic diseases: malaria and leishmaniasis. We will explore how the parasites identify and invade the host. This is a critical stage of the infection and we will characterise proteins involved as they are potential targets for drugs and vaccines against the parasites. Many of these recognition and interaction components are excellent candidates for the development of vaccines to interrupt the cycle of infection. We are also unravelling metabolic p ....Our program will investigate two major global parasitic diseases: malaria and leishmaniasis. We will explore how the parasites identify and invade the host. This is a critical stage of the infection and we will characterise proteins involved as they are potential targets for drugs and vaccines against the parasites. Many of these recognition and interaction components are excellent candidates for the development of vaccines to interrupt the cycle of infection. We are also unravelling metabolic pathways unique to the parasites using a mixture of genetic and computational tools complemented with sophisticated instrumentation to chemically identify the parasite�s entire repertoire of metabolic compounds. These pathways, absent from human hosts, are also highly vulnerable and we will feed the key steps into the drug development facet of the program. Our program also looks at how the parasites cause disease and how the host responds to the disease. We will explore the reactions of the immune system to infection and consequences of the body�s (often only partially successful) attempts to fight off the disease.Read moreRead less
Regulation Of Gene Expression: Biomolecular Interactions In Cellular Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,998,713.00
Summary
This team consists of three of Australia�s younger researchers Merlin Crossley, Joel Mackay and Jacqui Matthews (as Chief Investigators), who are recognized as authorities in the areas of gene regulation and the structural and functional analysis of proteins. They are joined by Mitchell Weiss, a world authority on blood development and clinical disorders,and Alexis Verger, a molecular and cell biologist recruited from France, both as Principal Investigators. Crossley, Mackay and Matthews have wo ....This team consists of three of Australia�s younger researchers Merlin Crossley, Joel Mackay and Jacqui Matthews (as Chief Investigators), who are recognized as authorities in the areas of gene regulation and the structural and functional analysis of proteins. They are joined by Mitchell Weiss, a world authority on blood development and clinical disorders,and Alexis Verger, a molecular and cell biologist recruited from France, both as Principal Investigators. Crossley, Mackay and Matthews have worked as a team for around six years to date, have published together in high-quality international journals, and have received anumber of accolades for their contributions to Australian science. For example, Crossley has won a number of national awards, including the Gottschalk Medal of the Australian Academy of Science; Mackay was recently awarded the Prime Minister�s Prize for Life Scientist of the Year, and Matthews won the only Charles and Sylvia Viertel Medical Research Fellowship to be awarded in 2003. The members of this team have collaborated extensively on the world stage and Crossley, Mackay and Matthews have also taken leadership roles in the Australian scientific community. Mitchell Weiss has been an important collaborator, exchanging reagents and advice, since he and Crossley trained together as postdocs in Stu Orkin�s lab at Harvard in the early 90s. Most recently Weiss, in collaboration with Mackay, has made important discoveries on a-globin production, which has led to several highly significant publications including a seminal paper in Cell in 2004.The program of research put forward in this proposal centres around understanding the mechanisms through which genes are switched on and off, using blood development as a model system, that is also fundamental to human life. The regulation of gene output is essential both during the development of an organism and throughout the course of its life. Problems with this regulation can result in many different disease states, most notably cancer, which includes the many different types of leukemias. At one level, gene output is controlled by networks of specific proteins known as transcription factors that interact both with each other and with DNA. Currently, however, the details surrounding which complexes regulate which genes and the processes that control the making and breaking up of the complexes are not well understood. Knowledge of how these interactions take place will put us in a position to control the output of chosen genes for therapeutic purposes. We propose to use a combination of cell biological, biochemical, and structural approaches to firstly shed light on these complexes and secondly develop reagents that can be used to manipulate the activity of specific genes.Read moreRead less
Immune Regulation, Effector Function And Human Therapy
Funder
National Health and Medical Research Council
Funding Amount
$11,474,346.00
Summary
The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, ....The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. Importantly, they are deciphering the intricate communication networks of these immune components and dissecting their modes of action. By understanding these complex processes, the team aims to harness the unique therapeutic properties of our own immune system and translate their findings into the clinic. The team is developing new immune-based therapies for use, either alone or in combination with existing chemotherapies to fight debilitating human diseases such as cancer and autoimmune disease.Read moreRead less
Interactions Between Adaptable Pathogens, Drugs And The Human Host
Funder
National Health and Medical Research Council
Funding Amount
$5,727,327.00
Summary
The Centre for Clinical Immunology and Biomedical Statistics (CCIBS) represents a collaboration between Royal Perth Hospital and Murdoch University that has brought together internationally recognised expertise in clinical immunology, experimental biology and innovation in biostatistics and computing. These resources have been applied to a broad range of research issues within the broad framework of HIV and hepatitis C disease and treatment. CCIBS has become a leading centre of research excellen ....The Centre for Clinical Immunology and Biomedical Statistics (CCIBS) represents a collaboration between Royal Perth Hospital and Murdoch University that has brought together internationally recognised expertise in clinical immunology, experimental biology and innovation in biostatistics and computing. These resources have been applied to a broad range of research issues within the broad framework of HIV and hepatitis C disease and treatment. CCIBS has become a leading centre of research excellence internationally, establishing a reputation for innovative approaches to host-viral interactions that are built on a long tradition of research into the population genetics of both human and viral genomes, combined with a willingness to negotiate complex computation and statistical challenges in order to faithfully reflect dynamic biological processes at a population level. An early recognition that large and integrated repositories of genetic and clinical data are fundamental to the research success in the genomic era has also led to the creation of the single most comprehensive repository of HIV genetic sequencing data in the world. The contributions that CCIBS has made to several distinct areas of research, including understanding viral adaptation to host immune responses, the development of genetic testing to predict drug hypersensitivity reactions, and causes of antiretroviral drug-associated toxicities, have been published in prestigious journals including Science, Nature, Nature Immunology, The Lancet, Proceedings of National Academy of Sciences, and The American Journal of Human Genetics, and have also resulted in numerous international collaborations that recognise the unique attributes that CCIBS has been able to bring to the global research effort aimed at understanding fundamental aspects of HIV and hepatitis C biology and treatment.Read moreRead less
Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand dise ....Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand diseases such as allergy, lupus, arthritis and leukaemia to develop novel therapies.Read moreRead less
Regulation Of Bone Resorption And Formation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,596,183.00
Summary
Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. ....Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. Osteoporosis results from an excess of bone breakdown over formation, and our Program aims to identify the factors that regulate these processes, and develop new therapies that can modify them. We will also determine what it is about bone cell properties that make some cancers, especially those of breast and prostate, particularly prone to spread to bone.Read moreRead less
Breast Cancer is a very common disease in women and although huge progress has been made in the last two decades, much remains to be done to improve our understanding of different types of breast cancer and its management. This program brings together the expertise of three senior researchers: 2scientists and 1 medical scientist. Dr Trench has an interest in identifying genes involved in cancers arising in patients who have a strong family history. She will use molecular methods and cohorts of p ....Breast Cancer is a very common disease in women and although huge progress has been made in the last two decades, much remains to be done to improve our understanding of different types of breast cancer and its management. This program brings together the expertise of three senior researchers: 2scientists and 1 medical scientist. Dr Trench has an interest in identifying genes involved in cancers arising in patients who have a strong family history. She will use molecular methods and cohorts of patients enrolled with Kathleen Cunningham Foundation for Research into Familial Breast and Ovarian Cancer to identify the genes responsible, assess their distribution in the population and determine whether these genes also play a role in non-familial cancers. Dr Khanna's work examines the complex array of enzymes that are responsible for maintaining the integrity of the DNA, and investigates how failure of these mechanisms leads to damage of the genetic material which ultimately results in cancer. It is known that genes involved in familial predisposition code for proteins that work as DNA repair enzymes. It is also known that different types of breast cancer exist, each with differing behaviour and response to treatment and that they are associated with specific genetic changes, including those associated with a familial predisposition. Prof Lakhani's interest lies in using microscopy and the latest molecular tools to refine the classification of these different types of breast tumour so that they can be managed appropriately by his surgical and oncological colleagues. A better understanding of the genetic changes and underlying biology of different types of breast cancer will lead to individualised and specific therapy for patients. This program brings together a unique combination, nationally and internationally, that investigates cancers at the level of genes and cells and translates the information to the clinic for the benefit of patient management.Read moreRead less