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. 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. 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. 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