Targeting Alpha-conotoxin MII To Inhibit Neuronal Nicotinic Acetylcholine Alpha3beta2 Receptors Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$218,334.00
Summary
Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique ....Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique tools with which to identify and determine the physiological role, played by the different native neuronal nAChRs. Moreover, they are unusually stable peptides and can withstand enzyme and acid treatment. These findings have encouraged us to pursue the viability of alpha-conotoxin MII as a new and selective antagonist for the neuronal nictotinic receptor alpha3 beta2 which is involved in nicotine addiction. The challenge and major goal of this project is to deliver alpha-conotoxin MII efficiently into the brain. A-Prof Toth has developed a novel drug-delivery system for the oral administration of drugs and peptides, which in their unmodified form are poorly absorbed or biologically unstable. In this project alpha-conotoxin MII will be combined with a specifically designed lipopolysaccharide delivery system . The delivery system can be specifically tailored to transport a wide variety of peptides through the different biological barriers. The peptides can be conjugated to the delivery system in such a way as to release the peptide after it has been absorbed (prodrug), or to form a biologically stable and active novel molecule. The outcomes of this work will include the first delivery system of nicotinic antagonists to the brain and new knowledge concerning the importance of the neuronal nictotinic receptor alpha3 beta2 in nicotine addiction.Read moreRead less
A Self-assembling And Self-adjuvanting Nanoparticular Therapeutic Vaccine Against Cervical Cancer
Funder
National Health and Medical Research Council
Funding Amount
$387,858.00
Summary
One in every three Australians will be diagnosed with cancer in their lifetime according to the Australia Cancer Foundation. The proposed project aims to develop pathogen-like bullets based on self-organized nanoparticles which would become a strong weapon against cervical cancer.
A Multiple Antigen Lipophilic Adjuvant Carrier (MALAC) System
Funder
National Health and Medical Research Council
Funding Amount
$141,500.00
Summary
We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and no ....We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and non-immunogenic. The system contains variables, which allow optimising its structural configuration. A small library of poly-functional MALAC system will be synthesised in a controlled step-by-step way combining solution or solid phase techniques, where the exact chemical structure (and the order of the different immunological peptide sequences) of the construct is pre-determined. The antigenicity and the protection against disease will be compared with antigenicity and protection generated using conventional vaccine carriers. We also aim to exploit the particulate-forming properties of the lipo-peptide amphiphiles, to form micro-particulate oral antigens, exploiting the phenomenon of particulate uptake from the GI tract by the GALT or other intestinal sites. The MALAC constructs will be administered orally followed by the measurement of the serum IgG. Vaccination via the oral route is highly desirable, since it can overcome many of the disadvantages inherent in administration by injection - e.g. poor patient acceptability, requirement of skilled medical personnel, risk of HIV and other blood-born diseases, restricted availability and sometimes, stimulation of the wrong type of immunity. Development of vaccines for oral administration make them much more widely available, permitting self-administration and improving the operation of Public-Health vaccination programs, particularly in developing countries.Read moreRead less
This project will unleash the potential of peptide drugs by overcoming their final barrier to widespread use, their synthesis. Plants naturally produce ultra-stable cyclic peptides. We will co-opt their machinery to produce in seeds, two drug leads that have potential as treatments for prostate cancer and chronic neuropathic pain. As an �organic� drug source, seeds have the potential to improve patient compliance and low-tech production systems will allow technology transfer to third-world natio ....This project will unleash the potential of peptide drugs by overcoming their final barrier to widespread use, their synthesis. Plants naturally produce ultra-stable cyclic peptides. We will co-opt their machinery to produce in seeds, two drug leads that have potential as treatments for prostate cancer and chronic neuropathic pain. As an �organic� drug source, seeds have the potential to improve patient compliance and low-tech production systems will allow technology transfer to third-world nations.Read moreRead less