Design And Engineering Of Adnectins For Diagnosis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$803,152.00
Summary
This project aims to engineer a naturally-occurring human protein, called an adnectin, to produce molecules that are able to bind specific targets in the human body, and as such may be used in the diagnosis and therapy of a range of diseases.
Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained a ....Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained and if this balance is lost then disease may result. A reduced level of cell death may result in cancers while too many dying can contribute to degenerative diseases such as Alzheimer's disease and stroke. Currently many of these diseases do not have effective treatments. We will determine the three-dimensional structures of key proteins involved in programmed cell death and use this information to design drugs that can interfere with the molecular processes involved in signalling cell death. Such drugs may prove useful new therapies in a wide range of diseases caused by a breakdown in the biochemical paths to cell death.Read moreRead less
Transport And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$592,023.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins and how the virus escapes from nerves to infect skin and cause disease. Such information on viral transport will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities. Finally this data will assist in understanding similar mechanisms for other viruses transported in nerve cells such as those causing shingles and rabies.Read moreRead less
Glycosyltransferase Effectors Of Enteropathogenic E. Coli And Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
This project aims to characterise the mechanisms of disease caused by bacterial pathogens including Salmonella and enteropathogenic E. coli. These pathogens cause a significant amount of diarrhoeal disease and mortality worldwide particularly in infants and in countries where water sanitation is poor. I aim to investigate the specific mechanisms the bacteria employ to manipulate and avoid our immune response during infection in order to better understand and combat diarrhoeal disease.
Directed Molecular Evolution Of G Protein-coupled Receptors For Stable And Functional Expression In Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$383,479.00
Summary
Approximately half of all prescription drugs on the market act on G protein coupled receptors (GPCRs). The mechanisms underlying GPCR function are mainly unknown due to a lack of structural information. No solved structures exist for any of the estimated 800 human GPCRs, making it difficult to design new drugs. By applying advanced protein engineering techniques I aim to produce human GPCRs in bacteria to ultimately acquire structural information, which will enable novel drug development.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.