Use Of Retroviral Expression Libraries To Characterise Mechanisms Of Drug Resistance In Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$362,545.00
Summary
At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsib ....At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsible. To date a number of mechanisms that cause resistance are known, but there are still unidentified mechanisms that are associated with drug resistance. The aim of our work is to use a new method to identify unknown drug resistance mechanisms in leukaemia. Once a mechanism is identified, we will determine its relevance in leukaemia by screening a number of patients that have shown resistance to treatment. If identified as a common mechanism of resistance in leukaemic patients, we will test possible agents able to prevent drug resistance that could be used in conjunction with drug during treatment, and to screen new drugs for susceptibility to resistance mechanisms. Diagnostic tests to detect the presence of the known resistance mechanisms prior to treatment could be used in selection of the most appropriate drug combinations for individual patients. Some of the known drug resistance mechanisms that occur in leukaemia are also operative in other forms of cancer and the project is of general relevance to cancer chemotherapy.Read moreRead less
Viral And Cellular Factors Affecting Early Steps In HIV Reverse Transcription
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
One of the key events in the life cycle of HIV is the conversion of viral RNA into a double stranded DNA intermediate. This process, called reverse transcription, is carried out by the viral enzyme reverse transcriptase (RT) in conjunction with other viral and cellular factors. While HIV RT has been extensively studied and RT inhibitors have been used in anti-retroviral therapy for HIV patients, other viral and cellular factors essential for efficient HIV reverse transcription have not been prop ....One of the key events in the life cycle of HIV is the conversion of viral RNA into a double stranded DNA intermediate. This process, called reverse transcription, is carried out by the viral enzyme reverse transcriptase (RT) in conjunction with other viral and cellular factors. While HIV RT has been extensively studied and RT inhibitors have been used in anti-retroviral therapy for HIV patients, other viral and cellular factors essential for efficient HIV reverse transcription have not been properly investigated and may represent a new class of anti-HIV targets.This project, based on our long standing (>10 years) research interest and experience, aims at identification of the viral and cellular factors particularly involved in the early steps of HIV reverse transcription.We have obtained preliminary data which lead to hypotheses regarding what kind of viral and cellular factors might be involved and their possible modes of action. Experiments have been designed to specifically prove or disprove these hypotheses. Thus this project will help us achieve a more comprehensive understanding on how HIV uses other viral and cellular factors, in addition to RT, to accomplish one of the mandatory stage of its growth (reverse transcription); and identify viral and cellular factors which can be further explored as new targets for anti-retroviral therapy. This is particularly important, as HIV resistance to current drug therapy has emerged as one serious issue facing HIV patients, and the HIV care communities.Read moreRead less