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EskITIs INsTITUTE
DRUG DIsCOVERY REsEARCH
“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
The Eskitis Institute - Multidisciplinary Drug Discovery
Our Research
Unique resources and capabilities
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.
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:
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:
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 semipurified 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.
•
Cancer (including prostate, pancreatic and breast cancer)
Neurodegenerative diseases (including Parkinson’s
disease, schizophrenia and Alzheimer’s disease)
Infectious diseases (including emerging antibioticresistant 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
(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
Quinn Group Projects
Project 1: Screening of prostate cancer targets against
natural product extracts
Fourier-Transform Mass spectrometry (FTMs) is an exciting
new method to probe interactions between proteins and ligands.
This project will use FTMs to screen some or all of the 18,000
optimised natural product extracts in the Nature Bank platform
against proteins critical in progression of prostate cancer. This
project offers an opportunity to apply modern drug discovery
techniques to natural products, while helping to develop the next
generation of prostate cancer drugs.
Project 2: Fragment-based drug discovery using fourier
transform mass spectrometry
Malaria is a parasitic disease that kills over 1 million people each
year, mostly young children. New drugs are desperately needed
to fight increasing parasite resistance. This project will use a
novel fragment-based approach to find new lead compounds for
development of new malaria drugs. Fragments, low molecular
weight compounds (MW<250) with weak binding affinities,
are becoming attractive starting points for drug discovery. This
project will apply a mass spectrometry (FTMs) method to screen
fragments from the Eskitis natural product library against malaria
proteins. This is a novel mechanism-based approach to exploit
natural product diversity for anti-malarial drugs.
Project 3: Synthesis of part structures of natural products to
build a fragment library
known naturally occurring fragments cover 56% of natural
product diversity space. Aligned with project 2, this project will
synthesise fragments derived from part structures of natural
products to cover 100% of natural product diversity space. This
approach will involve in silico analysis of this diversity space to
generate a minimum set of fragments, followed by synthesis.
Project 4: The use of natural product scaffolds in the
generation of novel chemical libraries
Natural products display chemical complexity and diversity often
not seen in synthetic collections and they inherently interact
with proteins making them an ideal source of unique scaffolds
for generation of screening libraries. Core ring structures found
in natural products but not present in commercial collections will
be used to generate chemically diverse libraries for use in drug
discovery programs or molecular probe research. This project
will create unique chemical libraries that can be tested against a
range of biological targets.
Project 5: Protein Fold Topology—a novel molecular
modelling approach to drug discovery
Natural products are made by nature via interactions with
biosynthetic enzymes. They also exert their effect as drugs
by interaction with proteins. We have shown that recognition
of the natural product by biosynthetic enzymes translate to
recognition of therapeutic targets. The concept of Protein Fold
Topology (PFT) describes cavity recognition points unrelated to
protein fold similarity. We are seeking automated methods to
interrogate these interactions.
Project 6: Synthetic lethal screening to identify new drugs to
fight advanced prostate cancer
Current treatments for advanced prostate cancer are largely
palliative, however new promising targeted therapeutics such
as antisense oligonucleotides on heat shock protein HsP27
and/or YB1are being developed. such treatment is effective
but causes tumours to develop resistance. This project will use
prostate cancer cells treated with siRNA to discover drugs from
Nature Bank that avoid treatment resistance. This project is an
opportunity to apply modern drug discovery techniques to
natural products, while helping to develop the next generation of
prostate cancer drugs.
Project 7: Old age and the liver epithelium
We are using confocal imaging to identify effects in cell
fenestrations to discover natural products that reduce the effects
of aging. This will involve establishing a confocal imaging assay
to detect cholesterol in lipid rafts. Nature Bank will be screened
against endothelial cells to find natural products that modulate
lipid rafts associated with fenestrations occurring in aging. This
is an opportunity to apply modern drug discovery techniques to
natural products, while investigating the aging process.
Project 8: Chemical biology using an annotated natural
product library on olfactory derived stem cells from
Parkinson’s disease patients
The project will annotate pure natural products contained within
the Nature Bank. Nature Bank includes 3250 pure compounds,
many with a known biological target. This annotated library will
be used to examine cells from Parkinson’s disease patients. Cells
will be investigated in order to identify compounds that correct
the phenotype.
Project 9: Development of reversible inhibitors of Factor XIa
Excessive formation of blood clots within the circulatory
system can cause thrombosis, stroke and heart disease. Risk
of thrombosis is especially high in patients recovering from
surgery. As many as 26,000 Australians suffer from venous
thromboembolism (VTE) each year and 10% of deaths in
Australian hospitals are thought to be caused by VTE. This
project is based on the discovery of potent FXIa inhibitors,
dysinosin A and clavatadine A in our laboratory.
EskITIs INsTITUTE
DRUG DIsCOVERY REsEARCH
“At Eskitis we are harnessing the
chemical diversity inherent in the
natural world to drive our research.”
Professor Ronald J Quinn AM, Director, Eskitis Institute
ResearcherID URL: www.researcherid.com/rid/A-7931-2008
Contact
The Eskitis Institute
Griffith University
Tel: +61 (07) 3 735 6000 Fax: +61 (07) 373 56001
[email protected], [email protected]
griffith.edu.au/eskitis
@eskitis (twitter)
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
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