Male Chlamydia Infections: The Key Role Of Macrophages In Testicular Dissemination And Disrupted Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$868,464.00
Summary
Male partners of couples seeking IVF, who are seropositive for Chlamydia, indicating a prior infection, often have significantly impaired sperm quality (reduced motility, increased DNA damage and abnormal sperm morphology). Our studies will define how Chlamydia are transported to the testis from the penis and how chronic chlamydial infection in the testis disrupts sperm development. We will also develop new antibiotic delivery systems to improve treatment of male chlamydial infections.
Novel ways of regulating epithelial transport. This project is intended to discover novel intracellular mechanisms that regulate the rate of ion transport by the lung, the gut and the kidney. It will not only provide new insights into how the body controls a process that is critical to animal life, but also provide new targets for the development of pharmaceuticals.
Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to ....Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to develop novel platinum(IV) compounds to the point where the industry partner can commercialise them.Read moreRead less
Unleashing the Hidden Chemical Diversity in Australian Fungi. This project aims to exploit an exclusive genomic resource consisting of >150 unique Australian filamentous fungi that has been built in a university-industry collaboration for genomic-guided biodiscovery. The genome sequence of these fungi revealed extensive hidden genetic instructions for production of novel biologically active molecules. The project will apply cutting-edge synthetic biology and chemical tools to tap into the hidden ....Unleashing the Hidden Chemical Diversity in Australian Fungi. This project aims to exploit an exclusive genomic resource consisting of >150 unique Australian filamentous fungi that has been built in a university-industry collaboration for genomic-guided biodiscovery. The genome sequence of these fungi revealed extensive hidden genetic instructions for production of novel biologically active molecules. The project will apply cutting-edge synthetic biology and chemical tools to tap into the hidden genomic potential of these Australian fungi. Expected outcomes of this project include new fine chemicals and lead molecules with desirable bioactivies. This will provide significant benefits to Australia's economy through the discovery of new pharmaceuticals, veterinary products and agrichemicals.Read moreRead less
Fertility Management of Koalas, Kangaroos and Wallabies. The aims of this work are to test a commercially available long-acting contraceptive on large populations of kangaroos and koalas, and to devise efficient, economic and practical ways of delivering these contraceptives to the animals. The outcome will be a system of controlling the number of these animals which is economically realistic and acceptable to national and international communities. The contraceptive is administered as a small, ....Fertility Management of Koalas, Kangaroos and Wallabies. The aims of this work are to test a commercially available long-acting contraceptive on large populations of kangaroos and koalas, and to devise efficient, economic and practical ways of delivering these contraceptives to the animals. The outcome will be a system of controlling the number of these animals which is economically realistic and acceptable to national and international communities. The contraceptive is administered as a small, subcutaneous implant in the back of the neck. It can be inserted very quickly and has no harmful side effects. A further outcome may be its adoption in other parts of the world, to the advantage of the company which manufactures it.Read moreRead less
Development of a topical treatment to replace surgical mulesing in sheep. 10,800 farms in Australia are sheep farms and a further 30,000 have sheep. Exports of wool earn over $2 billion annually. The animal rights campaign to ban mulesing has forced the industry to outlaw mulesing by 2010. Mulesing is largely confined to Australian Merino sheep and requires Australian research. If practical alternatives are not found costs will rise compromising the economic viability of many sheep farms. C ....Development of a topical treatment to replace surgical mulesing in sheep. 10,800 farms in Australia are sheep farms and a further 30,000 have sheep. Exports of wool earn over $2 billion annually. The animal rights campaign to ban mulesing has forced the industry to outlaw mulesing by 2010. Mulesing is largely confined to Australian Merino sheep and requires Australian research. If practical alternatives are not found costs will rise compromising the economic viability of many sheep farms. Chemical use on the breech will increase causing environmental contamination. A simple topical alternative to mulesing will allow farmers to economically manage flies and satisfy welfare imperatives. This will support rural communities and sustain Australia's export income from wool.Read moreRead less
Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this proje ....Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this project we will (i) prepare new anticancer active platinum complexes based on these two highly promising groups of compounds and (ii) determine how these drugs work and what happens to them when in biological environments.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient c ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient compliance. We will conduct critical chemical and biological experiments with a new series of potentially orally active iron chelators identified in our lab. The results from this project will be vital for the development of these compounds as pharmaceuticals.Read moreRead less
The biosynthesis of structural proteins in parasites. The socio-economic impact of parasitic diseases, in Australia and throughout the world, is enormous- they kill 2-3 million people per year and cost livestock industries billions of dollars per annum. Some are serious food and waterborne threats, such as the coccidia, because they are transmitted from person-to-person via the faecal-oral route, or via ingestion of contaminated water or food, or through the ingestion of cysts in raw or underco ....The biosynthesis of structural proteins in parasites. The socio-economic impact of parasitic diseases, in Australia and throughout the world, is enormous- they kill 2-3 million people per year and cost livestock industries billions of dollars per annum. Some are serious food and waterborne threats, such as the coccidia, because they are transmitted from person-to-person via the faecal-oral route, or via ingestion of contaminated water or food, or through the ingestion of cysts in raw or undercooked meat. They cause diarrhoea, which in some cases, can be life-threatening. We will understand how the coccidia protect themselves as they move from host to host and, through that understanding, develop new ways to control them and eliminate the suffering caused by parasitic diseases.Read moreRead less
Synthesis and evaluation of anti-microbial porphyrin adducts for the targeted inhibition of Porphyromonas gingivalis. At present the effectiveness of therapy for inflammatory disease of the gum tissue (periodontitis) is limited by the lack of a selective anti-microbial agent. The investigators have discovered a novel mechanism of binding of the blood product porphyrin by a unique receptor of a key pathogen implicated in this disease. By exploiting this knowledge a modified porphyrin linked to an ....Synthesis and evaluation of anti-microbial porphyrin adducts for the targeted inhibition of Porphyromonas gingivalis. At present the effectiveness of therapy for inflammatory disease of the gum tissue (periodontitis) is limited by the lack of a selective anti-microbial agent. The investigators have discovered a novel mechanism of binding of the blood product porphyrin by a unique receptor of a key pathogen implicated in this disease. By exploiting this knowledge a modified porphyrin linked to an antibiotic was shown to have a selective effect on the target organism. Refinement of this complex has the potential to provide a clinically useful, selective agent.Read moreRead less