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Davis_CapStat_130123-WEB

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  1. 1. “The Eskitis Institute is at the forefront of discovering new treatments for a wide range of critical diseases.” Professor Ian O’Connor, Vice Chancellor and President, Griffith University griffith.edu.au/eskitis EskITIs INsTITUTE DRUG DIsCOVERY REsEARCH
  2. 2. The Eskitis Institute - Multidisciplinary Drug Discovery Our Research Griffith University provides a setting of international standard for the pursuit of learning, teaching, research and professional practice. Griffith is ranked in the top 5% of universities worldwide. The Eskitis Institute is a flagship research centre of Griffith Universitythat focuses on drug discovery research. Eskitis offers an excellent environment for drug discovery research in areas such as: Cancer (including prostate, pancreatic and breast cancer) Neurodegenerative diseases (including Parkinson’s disease, schizophrenia and Alzheimer’s disease) Infectious diseases (including emerging antibiotic- resistant infections) • Global Health (including malaria, African sleeping sickness, tuberculosis and HIV) Eskitis researchers collaborate widely, with research partners on every continent, and hosts researchers and students from across the world. study with us The Eskitis Institute offers many opportunities for Masters and PhD study in drug discovery projects. Eskitis is a truly multidiscplinary research and training environment with an equal proportion of chemistry and biology researchers. Potential PhD study areas include: Medicinal chemistry Natural product chemistry (including marine invertebrates, plants and microorganisms) Traditional Chinese Medicines synthetic chemistry Bioaffinity Ms screening Neurobiology Cancer tumour biology Adult stem cell biology Parasitology Unique resources and capabilities Eskitis is located in two buildings, Eskitis 1 & 2, located on the outskirts of Griffith University’s Nathan Campus. Our research is supported by unique in-house capabilities, including the following: Nature Bank is a unique drug discovery platform based on natural products from Australia, China, Malaysia and Papua New Guinea. This biodiversity resource comprises >45 000 samples of plants and marine invertebrates, >18 000 extracts, >200 000 semi- purified fractions and >3 250 pure compounds. Nature Bank is an ideal resource for drug discovery research and is being actively used by projects in partnership with academic and industry groups. (visit nature-bank.com.au for more) Neuro Bank is a collection of well-characterised human olfactory neurosphere-derived (hONs) cells from over 200 neurology patients. Neuro Bank represents excellent models of neurological diseases to support research on Parkinson’s disease, schizophrenia and other diseases. Queensland Compound Library is an automated library of over 330 000 pure compounds from Australian chemists. The QCL is a national facility conceived to facilitate and drive interactions between chemists and biologists in Australia or overseas. (visit griffith.edu.au/qcl for more) Drug Discovery capabilities include a core of industry-standard drug discovery infrastructure including High Throuhgput screening. High throughput imaging is enabled by high content confocal screening systems, allowing the examination of the effect of compounds on individual cells. Mass Spectrometry facilities include 4.7 and 12 Tesla Fourier transform ion cyclotron resonance mass spectrometers (FTMs) for high resolution protein analysis. These instruments allow real-time observation and isolation of protein complexes. Nuclear Magnetic Resonance facilites include 500 and 600 Mhz units, allowing high resolution spectroscopy to quickly solve the structure of small molecules “The innovative work being conducted at the Eskitis Institute can accelerate and revolutionise our approach to fighting disease.” - Professor Ronald J Quinn AM, Eskitis Institute Director
  3. 3. Davis Group Projects Project 1: The use of natural product scaffolds in the generation of novel drug discovery screening libraries Natural products display chemical complexity and diversity often not seen in synthetic collections and they inherently interact with biomolecules (e.g. enzymes/proteins, DNA), making them an ideal source of unique scaffolds for screening library generation. By using natural product scaffolds we can generate chemically diverse libraries that can subsequently be used in drug discovery programs or molecular probe research. This project aims to create unique chemical libraries that can be tested against a range of biological targets. Isolation chemistry (e.g. HPLC, MPLC, gel permeation chromatography) will be undertaken on plant or marine samples that contain the desired scaffold, and then simple synthetic reactions (e.g. amide and carbamate formations, esterifications, reductive aminations) will be used to generate the novel chemical libraries. spectroscopic techniques (e.g. 1D and 2D NMR, Ms, IR, UV) will be used for the structure elucidation and characterisation of any purified natural products and synthetic compounds. Project 2: Cytotoxic natural products from Great Barrier Reef marine organisms Marine invertebrates (e.g. sponges or ascidians) have proven to be a rich source of novel and structurally diverse secondary metabolites. Many marine-derived natural products have also been shown to display unique and potent biological activities. specific cytotoxic examples include didemnin B, dehydrodidemnin B and ecteinascidin 743, which have all reached anti-cancer clinical trials. This project aims to discover new cytotoxic natural products from Great Barrier Reef marine invertebrates using bioassay-guided fractionation protocols. Fractionation of crude extracts will be performed using a variety of chromatographic techniques such as HPLC, and size-exclusion chromatography. Biological evaluation of the fractions generated using high content screening and cancer cells will indentify bioactive samples. Pure compounds will have their chemical structures determined using 1D and 2D NMR, Ms, UV/vis and IR spectroscopy. Chemical degradation or derivatisation reactions may also be used to assist the structure elucidation studies. Potent cytotoxic agents will be screened against a number of human prostate, breast and bladder cancer cell lines. Project 3: New chemistry and anti-infective agents from endophytic fungi Fungi are now generally accepted as the largest group of organisms on Earth after the insects; as a working figure the Global Biodiversity Assessments accepted the estimate of 1.5 million species of fungi. Approximately 72,000 species have been described so far (only 5% of 1.5 million) and of this number only a portion have been chemically investigated. Thus the use of fungi in the search for new secondary metabolites has a strategic advantage since this unique resource has been superficially explored. This project aims to discover new natural products produced by fungi isolated from Queensland plants. Fermentation of taxonomically unique fungal strains will be performed and the resulting crude fungal extracts will be fractionated using a variety of chromatographic techniques such as MPLC, HPLC and size-exclusion chromatography. Pure compounds will have their chemical structures determined using 1D and 2D NMR, Ms, UV/vis and IR spectroscopy. All compounds purified during these studies will be tested against a panel of microbes known to be associated with nosocomial infections such as multi-drug resistant Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans. Project 4: Antimalarial compounds from nature Each year there are around 600 million clinical cases of malaria and over 1 million deaths due to this disease. Approximately 3.2 billion people are at risk of contracting malaria, including people in Papua New Guinea, Indonesia and regions of northern Australia. The frontline defence against malaria is drug prophylaxis or treatment but this is under threat due to parasite drug resistance to most antimalarials. Consequently there is an urgent need for new antimalarial drugs with unique modes of action. This project aims to identify new leads or drugs for malaria from Australian, Chinese or Papua New Guinean biota. Initially biota extracts or fractions will be screened for their ability to inhibit the malaria parasite Plasmodium falciparum. Isolation chemistry will be undertaken on active extracts or fractions using mass-directed or bioassay-guided fractionation. The chemical structures of all compounds purified will be determined by a variety of spectroscopic techniques (1D and 2D NMR, Ms, UV, IR). The antimalarial activity of all compounds will be assessed and where appropriate structure modifications will be made using simple degradation or derivatisation chemistry in order to obtain important structure-activity relationships. Mechanism of action studies will also be pursued where appropriate. Project 5: Anti-infective agents from Australian endemic plants This project aims to discover new anti-infective compounds from endemic Australian plants. Proton NMR or mass-directed fractionation using a number of separation techniques such as HPLC, and size-exclusion chromatography will be employed to purify plant-derived metabolites. All new natural products will be spectroscopically characterised using 1D and 2D NMR, UV, IR, CD and Ms data. Crystallographic studies and chemical derivatisation or degradation reactions on the isolated compounds will be pursued where possible. All compounds purified during these studies will be tested for ability to inhibit the growth of parasites or bacteria associated with human infectious diseases.
  4. 4. Location The Eskitis Institute Eskitis 2 Building (N75) Griffith University Brisbane Innovation Park, Don Young Road Nathan Qld 4111 Australia Griffith University CRICOS Provider Number 00233E Contact The Eskitis Institute Griffith University Tel: +61 (07) 3 735 6000 Fax: +61 (07) 373 56001 eskitis@griffith.edu.au, r.davis@griffith.edu.au griffith.edu.au/eskitis @eskitis (twitter) ResearcherID URL: www.researcherid.com/rid/B-1689-2008 ‘We are going back to nature to look for new compounds that can be developed into drugs to fight infectious diseases, such as malaria and multi-drug resistant bacterial infections.’ Dr Rohan Davis, Eskitis Institute Front cover images (Clockwise from top left): Professor Ronald J Quinn AM, the Eskitis 2 Building, Professor Ian O’Connor, interior of QCL robot, eucalyptus leaves EskITIs INsTITUTE DRUG DIsCOVERY REsEARCH

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