Download Details of our honours course and available projects in 2017.

Honours in Pharmacology
2017
Projects and Program Information
Message from the Head of Discipline and Honours Coordinator
Prof Robert
Vandenberg
Head of Discipline
A/Prof Rachel Codd
Honours Coordinator
The Discipline of Pharmacology invites you to apply to undertake a research year in
the fourth year of your studies (Honours in Pharmacology). This program is designed
to give students a greater depth to their studies and to promote research-led inquiry
and intellectual endeavour. Students who complete Honours in Pharmacology will be
equipped with a skill set that improves their employment prospects in industry or
government, and is a requirement for undertaking postgraduate studies in
Pharmacology. The Discipline of Pharmacology has a group of dedicated academic
staff and affiliates who are conducting cutting-edge research across a variety of
fields, including asthma pharmacology, cancer therapeutics, chemical biology,
chronic inflammation and pain, clinical pharmacology, drug design and development,
drug delivery, protein folding, neuropharmacology, pain management,
pharmacogenomics, pharmacoinformatics and toxicological QSAR, therapeutic
cannabinoids, transporter biology and pedagogical research. This booklet is designed
to provide further details about the Honours program and describes the projects on
offer to students in 2017. We hope you’ll join us for an enjoyable and rewarding
Honours year. For further enquiries, please contact the Honours Coordinator, A/Prof
Rachel Codd: [email protected]
I’m interested in Honours in Pharmacology – what do I do next?
Please join us for our Honours Information session, which is to be held on:
Friday 16 September at 12 noon in the Norman Gregg Lecture Theatre (Edward Ford Blg).
At this session, the Honours Coordinator will provide further details on the structure of the program and staff
will give an overview of their research areas. After formal proceedings, you are warmly invited to a lunch in
the Bosch precinct courtyard from 1 pm, where you can talk with individual staff members about their
projects. Over the next 2 months, you should elect your preferred supervisor(s) and projects and submit your
Honours Preference Form (end of this booklet) to the Honours Coordinator by Friday 18 Nov 2016.
Students can elect to start their Honours year in S1 or S2. To enable academics to plan their group
composition, students who wish to begin in S2 should make their supervisor selection at the start of the year.
In addition to lodging your Honours Preference Form with Pharmacology, you must lodge an application for
Honours with the Faculty of Science via the Sydney Student portal. Further information is available on the
Faculty of Science URL: http://sydney.edu.au/courses/bachelor-of-science-honours
Am I eligible for Honours in Pharmacology?
All students with a strong record in Pharmacology are encouraged to apply to the Honours Program.
Students are required to have completed a major in the area relevant to Honours and have a Science
Weighted Average Mark (SCIWAM) of ≥ 65. Depending upon demand, the nominal acceptance cut-off for
Honours in Pharmacology may be increased to ≥ 68. If you are uncertain about your eligibility, you should
arrange to meet with the Honours Coordinator and have your academic transcript available for review.
Selecting a Research Group
This booklet describes projects that represent the research interests of the academics in Pharmacology and
several affiliates. Staff members have provided project details and the link to their research profile on the
Sydney Medical School website. Honours is the beginning of your research career and you should carefully
consider the selection of the most suitable research leader to support your research development. Measures
of research activity include external grants – which may be funding your project – and publications – which
reflect the quality, impact and rigour of the research being conducted by the group. It is also wise to talk with
current students in the group to gain first-hand knowledge of the day-to-day science and style of supervision.
What will I do during my Honours year?
You will undertake a research project under the direct supervision of a member of staff, and as part of their
research group. You will deliver two oral presentations to the Discipline (April/May (0%), Oct/Nov (20%)),
write a 16-page combined literature review and research proposal (June (10%)) and write a 50-page thesis
detailing the aims, methods, results and discussion of your project (Oct, 60%). Your supervisor will award
you a mark (10%) that reflects your research dedication, competency and aptitude.
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Academic Staff in Pharmacology
Namea
Locationb
Research Area
A/Prof Jonathon Arnold
BRMI: 503
Endogenous cannabinoid system, behavioural
neuropharmacology
A/Prof Elena Bagley
BKB: W326
Synaptic physiology/plasticity, synaptic
function/dysfunction, brain disorders
A/Prof Sinthia Bosnic-Anticevich
WIMR: 4017
Primary health care research: asthma, inhaler devices
Prof Nicholas Buckley
BKB: 301
Clinical pharmacology and toxicology
Dr Kellie Charles
BKB: 306
Cancer pharmacology, tumour-immune cell interactions
Prof Macdonald Christie
BKB: W300
Cellular/molecular neuropharmacology, pain pathways
and pain therapeutics
A/Prof Rachel Codd
BKB: 274
Chemical biology and medicinal chemistry, metals in
biology
Dr Tina Hinton
CPC: 2N12
CNS GABAergic neurotransmission, schizophrenia,
pedagogical research
Dr Hilary Lloyd
BKB: 307
Neurotransmitter release mechanisms, neuroprotection
Dr Slade Matthews
BKB: 394C
Machine learning in biomedicine, toxicological QSAR
Dr Brent McParland
BKB: 215
Asthma pharmacology, human bronchus, smooth muscle
Prof Michael Murray
MFB: L1
Pharmacogenomics, cancer therapeutics
A/Prof Renae Ryan
BKB: 212
Biophysics of membrane transport, glycine transport
A/Prof Margaret Sunde
BKB: 214
Protein biophysics, protein misfolding, amyloid fibril
formation and structure
A/Prof Daniela Traini
WIMR
Respiratory drug delivery science, asthma, COPD,
bronchiectasis
Prof Robert Vandenberg
BKB: 210
Molecular biology, glutamate transport,
electrophysiology
Prof Paul Young
WIMR
Respiratory diseases, medical devices, lung-specific
advanced formulations
Namea
Locationb
Research Area
Dr Karin Aubrey
KOL
Models of neuropathic pain
A/Prof Kay Double
BMRI
Parkinson’s disease, metalloneurochemistry
A/Prof Sarah Hilmer
KOL
Geriatric medicine and clinical pharmacology
Prof Michael Kassiou
CHEM 546
Drug design and medicinal chemistry, CNS active
compounds
Dr Chris Vaughan
KOL
Chronic pain and endocannabinoids
Affiliates
a
Generic format for e-mail: [email protected] (eg, [email protected]).
b
BKB = Blackburn building (D06). BMRI = Brain & Mind Research Institute. WIMR = Woolcock Institute of
Medical Research. CPC = Charles Perkins Centre. MFB = Medical Foundation Building. RNSH = Royal North
Shore Hospital. CHEM = Chemistry. KOL, Kolling Building.
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Pharmacology is a broad discipline. Where will you fit?
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A/Prof Jonathon ARNOLD
Cannabinoid Research Group
Lambert Initiative of Cannabinoid Therapeutics
Room 503, Brain & Mind Centre
[email protected]
Cannabis is the most widely used illicit drug in the world and cannabinoids are
increasingly being utilised in therapeutics. For 20 years I have focused on the
preclinical pharmacology and therapeutic application of the cannabinoids. My
first major discovery was that phytocannabinoids reverse resistance to
anticancer drugs. I have also isolated genes that modulate the effects of
cannabinoids on the brain. My current work examines the efficacy of
cannabinoids in various preclinical models of disease including childhood
epilepsy, PTSD, addiction and schizophrenia.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/jonathon.arnold.php
Research group (2016):
1 Post-doc, 4 PhD students, 2 Honours students
PROJECT 1
PRECLINICAL DRUG DEVELOPMENT OF CANNABINOIDS FOR THE TREATMENT
OF CHILDHOOD EPILEPSY
Dravet syndrome is a devastating form of childhood epilepsy that has a mortality rate of 16%. Seizures often commence
within the first year of life and significant developmental delays in cognition, speech and motor skills become evident
during childhood. Current treatments for Dravet syndrome are grossly inadequate and many families resort to using
illegal cannabis extracts out of desperation. This is not without good reason, as there are numerous reports of cannabis
dramatically reducing seizures and improving the health of children with Dravet syndrome. While conventional animal
models of epilepsy have assisted in the development of anti-epileptic drugs, they have failed to find new agents that
treat paediatric epilepsy. This project will utilise Dravet syndrome mice that provide a new platform to discover novel
therapeutic agents for childhood epilepsy. Genetic mutations observed in Dravet syndrome have been introduced to
mice that faithfully reproduce key features of the disorder, such as early-onset seizures, mortality and developmental
delays in cognitive, motor and social function.
Cannabis is a complex mixture containing numerous cannabinoid compounds, therefore the active constituent/s
need to be elucidated. Cannabidiol (CBD) is currently being tested in clinical trials for its efficacy in treating childhood
epilepsy. CBD lacks psychoactivity and has a favorable toxicity profile. We will also assess the efficacy of other promising
phytocannabinoids such as tetrahydrocannabinolic acid (THCA), cannabigerol (CBG) and cannabichromene (CBC). We
will assess whether the cannabinoids protect against seizures and mortality in Dravet mice. Our proposed studies will
also examine whether cannabinoids halt developmental delays in cognitive, social and motor function.
TECHNIQUES
drug administration, transgenic mice, behavioural analysis, EEG measurements,
immunohistochemistry, dendritic morphology analysis
Selected publications
•
•
•
•
•
•
•
Arnold, J.C., Report on the medical applications of cannabis and the cannabinoids. Legislative Assembly of the Australian
Capital Territory, 2015. p. 1-32.
Allsop, D., R. Kevin, and J.C. Arnold, Cannabis: Pharmacokinetics and Pharmacodynamics in relation to Patterns of Use in
Handbook of Drug and Alcohol Studies K. Wolff, J. White, and S. Karch, Editors. 2015, SAGE: London, UK.
Karl, T. and J.C. Arnold, Genetic Mouse Models for Cannabis Abuse & Dependence. , in Handbook of Behavioral Genetics of
the Mouse. 2014, Cambridge University Press
Swift W, Wong A, Li KM, Arnold JC, McGregor IS (2013). Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency
and Cannabinoid Profile. PLoS One 8(7): e70052.
Spencer JR, Darbyshire KME, Boucher AA, Kashem MA, Long LE, McGregor IS, Karl T, Arnold JC (2013). Novel molecular
changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: A hippocampal proteomic study
in mice. Front Cell Neurosci 7(15): 1-13.
Karl, T., D. Cheng, B. Garner, and J.C. Arnold, The therapeutic potential of the endocannabinoid system for Alzheimer's
disease. Expert Opin Ther Targets, 2012. 16(4): p. 407-20.
Chohan, T.W., A.A. Boucher, J.R. Spencer, M.S. Kassem, A.A. Hamdi, T. Karl, S.Y. Fok, M.R. Bennett, and J.C. Arnold,
Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and
HPA axis activity in adolescent mice. Schizophr Bull, 2014. 40(6): p. 1272-84.
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A/Prof Elena BAGLEY
Synaptic Physiology and Plasticity
Blackburn Building, 9351-4895
[email protected]
Our research group is interested in normal synaptic function and synapse
dysfunction. Synaptic dysfunction is emerging as a key player in many
brain disorders. We use patch-clamp electrophysiology in brain slices,
immunohistochemistry and biochemical assays to study synaptic
properties and synaptic plasticity that may participate in physiological
or pathophysiological processes. These honours projects focus on how
endogenously released opioid peptides alter synaptic function and
plasticity in the amygdala. Fear and anxiety are adaptive responses that
allow animals to defend themselves against harm. Neural circuits in the
amygdala are key for fear memory acquisition and storage but also for
reducing the fear response (extinction). Extinction of the fear response
relies on a special group of GABAergic interneurons in the amygdala, the
intercalated cells.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/bagleye.php
Research group (2016):
Sarah Kissiwaa (PhD student), Gabbi Gregoriou (PhD student), Sahil Patel (PhD
student), Danashi Medagoda (Honours Student)
PROJECT 1
Does fear change endogenous opioid expression in the amygdala?
Enkephalins are endogenous opioids that are strongly expressed in the amygdala
and are thought to be involved in several aspects of fear. Mice deficient in the
enkephalin precursor, preproenkephalin, are highly anxious and aggressive.
Intercalated neurons (IA in figure) express very high levels of the μ-opiate
receptor (MOR) and the endogenous opioid ligand enkephalin. Stress or anxiety
may change opioid receptor or metabolizing enzyme expression in the amygala.
This project will determine whether a fearful experience alters the expression of
elements of the endogenous opioid system in the intercalated cells.
TECHNIQUES
Immunohistochemistry, biochemistry
PROJECT 2
Does fear endogenous opioid function in the amygdala?
Endogenous opioids are significant regulators of synaptic glutamate and GABA
release in the intercalated region of the amygdala. Mice deficient in the
enkephalin precursor, preproenkephalin, are highly anxious and aggressive.
Intercalated neurons (IA in figure) express very high levels of the μ-opiate
receptor (MOR) and the endogenous opioid ligand enkephalin. In this project we
ask whether fear learning alters endogenous opioid regulation of
neurotransmitter release in the intercalated region of the amygdala.
TECHNIQUES
Patch-clamp electrophysiology, immunohistochemistry, optogenetics
PUBLICATIONS.
Sengupta A, Winters B, Bagley EE, McNally GP. (2015) Disrupted Prediction Error Links Excessive Amygdala Activation to Excessive
Fear. J Neurosci. 2016 Jan 13;36(2):385-95.
Bagley E.E. (2014) Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after
chronic morphine treatment. Front Pharmacol. 24;5:148.
Connor M, Bagley EE, Chieng BC, Christie MJ. β-arrestin-2 knockout prevents development of cellular μ-opioid receptor tolerance but
does not affect opioid-withdrawal-related adaptations in single PAG neurons. (2014) Br J Pharmacol.
Bagley EE, Westbrook GL. (2012) Short-term field stimulation mimics synaptic maturation of hippocampal synapses. Journal of
Physiology 2012 Apr 1;590 (Pt 7):1641-54.
Bagley EE, Hacker J, Chefer V.I., Chieng B.C. Mcnally G.P., Shippenberg T.S. & Christie M.J. GAT-1 transporter currents excite
GABAergic neurons to produce opioid withdrawal behaviour. Accepted Aug 17th 2011 Nature Neuroscience,
Bagley EE, Gerke MB, Vaughan CW, Hack SP, Christie MJ. (2005) GABA transporter currents activated by protein kinase A excite
midbrain neurons during opioid withdrawal. Neuron. 45:433-45.
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A/Prof Sinthia BOSNIC-ANTICEVICH
Quality Use of Respiratory Medicines Group/
Clinical Management
Room 4017, Woolcock K26
[email protected]
Our group focuses on innovative and effective ways to better manage chronic
respiratory illness. This involves. Research students are important members of
our research group and we promote a culture of learning through sharing and
collegial support.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/sinthia.bosnicanticevich.php
Research group (2016):
Dr Vicky Kritikos, Dr Sharon David, Amanda Elaro, Biljana Cvetovski, Pamela
Srour, Rachel Tan, Marima Toumas, Sarah Barbara, Elizabeth Azzi, Samantha
Khuu.
PROJECT 1
KNOWING YOUR NOSE AND HOW TO TREAT IT
Will suit a student who is interested in health outcomes
Allergic rhinitis is a highly prevalent condition. It is known to cause significant
impact on an individual’s quality of life and is a common trigger for poor asthma
control. In fact, approximately 90% of people with asthma have allergic rhinitis yet
our recent data indicates that approximately half of these people have never had
allergic rhinitis diagnosed by a doctor and less than one third of them are taking
appropriate treatment, despite experience moderate to severe symptoms.
We are interested in finding out why and to develop an effective intervention to
solve this problem.
TECHNIQUES
Students will learn to develop evidence based interventions and pilot test them.
PROJECT 2
HEALTH CARE DELIVERY NETWORKS IN PRIMARY CARE
Will suit a student interested in developing clinical process to support better care delivery
A key component of effective respiratory disease management is the regular review
of patient disease status in order to ensure that diagnosis of illness is early,
accurate and directed towards the most effective care pathway. In respiratory
illness, there is a lack of regular review of illness and consequently patients with
respiratory illness often receive a late diagnosis and medication management is
suboptimal. This research explores the UK-based effective evidence-based
programs Optimum Patient Care (OPC), with the aim of implementing and
evaluating it into the Australian primary health care setting. As a result a novel
model of care delivery, will be evaluated. This research has implications for the
management of respiratory illness in the future.
TECHNIQUES
Implementation science and translational research methodologies.
PROJECT 3
WHAT CAN MEDICATION USE TELL US ABOUT THE SEVERITY OF ASTHMA
Will suit a student who is interested in exploring the way in the patterns of medication use can help us
understand patient behaviour and clinical needs.
Over the last decade, severe asthma has become a defined sub-category of
asthma, characterized by high dose medication use and difficult to treat
symptoms. One of the medications more commonly used to treat severe asthma is
oral glucocorticosteroids (OCS). However, OCS are convenient to take and certainly
provide an easier route of medication administration compared to inhaled
medicines, often used incorrectly and irregularly. This research is based on the
hypothesis that some patients do not take their inhaler medicines regular but
rather turn to OCS, giving the overall impress that they suffer from severe asthma
rather than the reality of non-adherence to their inhaler medicines. This research
will explore this hypothesis and identify the truth behind OCS in the community.
TECHNIQUES
Students will be exposed to a mixed methods research approach.
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Prof Nicholas BUCKLEY
Clinical Pharmacology & Toxicology Group
Rooms 470/474A/301, Blackburn Building
[email protected]
We are a multi-disciplinary collaboration of researchers, our goal is to
integrate the clinical, epidemiological and laboratory research in human
toxicology in order to investigate a range of human toxicology problems.
We have established the two largest clinical cohort studies on poisoning
in the world. These enable us to conduct population based studies into
poisoning and its treatments. Honours projects carried out within the
group offer an excellent introduction to the emerging and exciting field
of “big data” – using large datasets to reveal trends, patterns and
associations that can have big public health impact. Projects are wellsuited to students interested in moving into research areas of
epidemiology, public health, or clinical medicine. Below are two
examples, but with the resources and datasets available to the group
many other research possibilities are also available.
Research interests & pubs:
http://sydney.edu.au/medicine/people/academics/profiles/nicholas.buckley.php
Research group (2016):
Kate Chitty, Rose Cairns, Nick Osborne, Kat Kirby, Andrew Dawson
PROJECT 1
Epidemiology of antidepressant use and poisoning in the elderly in Australia
involves joint supervision with Dr Rose Cairns
This project will extract data from the Poisons Information centre database and
the national coronial information system (from 2000 to 2015) and compare this
to publically available data on Australian use of antidepressants in those aged
over 65 years in different locations in Australia. Students will review the
evidence for efficacy in this age group, explore trends over time in the use of
antidepressants in the elderly, the impact on non-fatal and fatal poisoning and
suicide in Australia, and relationship to geographic location and guidelines.
This project may also involve utilising routinely collected Australian prescription
data to explore doctor’s prescribing in this age group (dose, co-prescription, etc)
TECHNIQUES
Epidemiology, Pharmacoepidemiology, statistics, database analysis
PROJECT 2
Links between alcohol, medicines, inflammation and depression
involves joint supervision with Dr Nick Osborne and Dr Kate Chitty
This project will examine data from the US (NHANEs). Participants in this study
have a range of medical tests and questionnaires for health biomarkers.
Biomarkers of inflammation and health, questionnaire data on depression and
drug use will be use to answer the question about the relationship between
inflammation and depression, as well as considering the effects of alcohol
consumption, other pharmaceutical use (prescription and recreational) and
demographic factors on this relationship. The study would include recruiting a
small cohort of Sydneysiders to examine the question in the Australian context
(questionnaire and blood sample).
TECHNIQUES
Epidemiology, statistics, database analysis, clinical research, questionnaire design
Other opportunities
There are other ongoing studies and data sources available to the group that can be utilised to suit a wide
array of research interests. Here are just a few examples:
• Using the “UK Biobank” study of 500000 participants to measure the risk factors involved in the
initiation and progression of osteoporosis
• Investigating the role that a positive blood alcohol concentration has in suicides in Australia
• Linking medicines data to coronial data to determine drugs that are over-represented in suicides
• Comparing the role of alcohol in deliberate self-poisonings in Australia versus Sri Lanka – what part
do cultural alcohol “norms” play?
• Examine liver and alcohol biomarkers from clinical studies/trials of paracetamol poisoning.
Have other ideas? Come talk to us and we can help you design your own project around a specific area
of interest!
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Dr Kellie CHARLES
Cancer Pharmacology Laboratory
Room 306, Blackburn Building
[email protected]
Our research group is primarily focused on how chemotherapy drugs
(currently used and new agents) alter the local and systemic inflammatory
response. Our group has shown that inflammation impacts the
pharmacological response to chemotherapy in terms of response and toxicity.
We conduct both clinical and preclinical investigations of the response and
toxicity induced by chemotherapy drugs to further understand how to
improve the treatment of patients with cancer. New drugs are also tested in
our research group to limit the toxicity of the current anti-cancer
treatments.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/kellie.charles.php
Research group (2016):
3 PhD Students, 1 honours student, 1 TSP student
PROJECT 1
IMPACT OF INFLAMMATION ON CHEMOTHERAPY OUTCOMES
This challenging project is designed for an honours student with an interest and background knowledge in
pharmacology, cancer and immunology. Our clinical trial data shows that lung cancer patients with
inflammation have poorer response to chemotherapy and shorter survival. However, we do not understand
the reasons underlying this relationship nor if it relates to the wider cancer population that do not fit
clinical trial eligibility criteria. This pharmacoepidemiology project will investigate real-world clinical data
and pharmacy records to determine the impact of systemic inflammation on chemotherapy dosing and
outcomes in colorectal patients in the community.
TECHNIQUES
Clinical data analysis and biostatistics
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Prof Mac CHRISTIE
Neuropharmacology of Pain and Opioid Mechanisms
Room W300, Blackburn Building
[email protected]
Two major areas of study in pain and opioid mechanisms aim to; (1) understand
mechanisms of adaptation in ion channels and cell physiology contributing to
chronic pain states, and develop of novel pain therapeutics to target these
mechanisms, and (2) understand the molecular and cellular mechanisms of
opioid tolerance and physical dependence with the goal of improving opioid
therapeutics. We use patch clamp electrophysiology in mammalian cells and
spinal cord slices integrated with behavioural models of chronic pain. It is likely
that only one of the two possible projects will be run in 2016.
Research interests & publications:
http://sydney.edu.au/medicine/people/academics/profiles/mac.christie.php
Research group (2016):
4 postdocs, 1 research assistant, 1, PhD student, 1 MPhil student, 1 Hons student
PROJECT 1
MECHANISMS OF ACTION OF NOVEL ω-CONOTOXINS IN PAIN STATES
Will suit a student with interests in behaviour/cellular physiology
One ω-conotoxin, Prialt (ω-conotoxin MVIIA), that irreversibly antagonizes N-type voltage-gated calcium
channels is currently used to help manage severe chronic pain but it produces severe on target side-effects
that limit its usefulness. We have identified a series of novel ω-conotoxins, starting
with CVID, that reversibly inhibit N-type channels and show an improved side effect
profile after intrathecal administration in neuropathic pain. The therapeutic index
of this series of conotoxins is related to the reversibility of inhibition of N-type
channels, a process that changes in neuropathic pain states due to an as yet unknown
adaptation of channel properties. The present project will involve investigation of
these adaptations in a chronic inflammatory pain model that is well established in
our laboratory. You will develop skill in the inflammatory pain model in rats,
measuring behavioural outcomes and then determine changes to basic N-type calcium channel kinetics and
binding kinetics of several novel ω-conotoxins using patch clamp electrophysiology in sensory neurons
isolated from animals displaying signs of inflammatory pain. If time permits you will examine potential
adaptations to N-type channel composition in inflammatory pain using real-time PCR.
TECHNIQUES
behavioural assays in animal models, neuron isolation,
PROJECT 2
BIASED SIGNALING OF NOVEL OPIOID RECEPTOR AGONISTS
Will suit a student with interests in cellular physiology/ molecular pharmacology
We have developed a novel series of opioid receptor agonists based on a new tetrapeptide structure. We have introduced functional groups into the peptides to
facilitate blood brain barrier penetration. This project will determine whether these
agonists show a similar signaling bias to the parent peptide compounds, which would
suggest they have novel capcity to produce analgesia versus adverse effects such as
tolerance. You will learn to culture mammalian cells expressing µ-opioid receptors,
measure receptor endocytosis and phosphorylation with immunohistochemistry and
confocal microscopy, and receptor function with patch clamp electrophysiology.
TECHNIQUES
Cell culture, immunochemistry, patch clamp electrophysiology, simple kinetic analyses
Selected publications
[1] Jayamanne A, Jeong H J, Schroeder C I, Lewis R J, Christie M J and Vaughan C W (2013). Spinal actions of ω-conotoxins, CVID,
MVIIA and related peptides in a rat neuropathic pain model. Brit J Pharmacol. 170, 245-254.
[2] Yousuf A, Miess E, Sianati S, Du Y-P, Schulz S, Christie MJ (2015). The role of phosphorylation sites in desensitization of µ-opioid
receptor. Mol Pharmacol. (in press, doi:10.1124/mol.115.098244).
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A/Prof Rachel CODD
Chemical Biology in Drug Design Laboratory
Room 274, Blackburn Building
[email protected]
Projects in my group blend aspects of chemistry, biochemistry,
microbiology and biotechnology. We are interested in a class of bacterial
compounds called ‘siderophores’ used to treat conditions that arise from
iron dyshomeostasis, with broader applications as anti-infective and anticancer agents. Some projects use traditional chemical synthesis as part of
the drug design approach. Other projects use bacterial fermentation and
precursor-directed biosynthesis to produce known and new compounds,
which we purify using a specialist technique developed in our group.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/rcodd.php
Research group (2016):
2 Postdoctoral Research Associates, 3 PhD students, 2 Honours students
PROJECT 1
HIJACKING THE BACTERIAL BIOSYNTHETIC MACHINERY FOR NEW SIDEROPHORES
Will suit a student with interests in microbiology/biochemistry and chemistry
Siderophores are low-molecular-weight organic compounds
produced by bacteria which bind iron(III) with high affinity.
Bacteria produce these compounds as a mechanism to supply
iron to the cell, as essential for growth. As metal-binding
molecules, siderophores have a number of applications as
drugs, particularly in conditions that involve metal ion
dyshomeostasis. The siderophore desferrioxamine B (DFOB) (structure above) produced by the soil
bacterium Streptomyces pilosus, is used to treat secondary iron overload, which occurs as a complication
of transfusion-dependent genetic blood disorders, including β-thalassemia. This structurally complex
molecule is difficult to prepare in the laboratory, and industrial-scale production relies on bacterial
fermentation. In an exciting development in our group, we have discovered that we can commandeer the
biosynthetic machinery of S. pilosus and drive the bacterium to produce unusual analogues of DFOB. This
is a significant discovery, since these new compounds could have properties superior to DFOB as the
clinical parent. In this project, you will culture S. pilosus in the presence of new building blocks to
generate new DFOB analogues for purification and characterisation. In a new twist, the target analogue
could be amendable to down-stream semi-synthetic chemistry to further expand structural diversity.
TECHNIQUES Microbiology, LC-MS, Coordination chemistry, Semi-synthetic chemistry
PROJECT 2
THE SIDEORPHORE METABOLOME OF SALINISPORA TROPICA: A RECORD BREAKER
Will suit a student with interests in microbiology/biochemistry (no chemistry required)
The focus on the discovery of bioactive compounds from
natural sources has shifted in recent times from terrestrial
bacteria to marine bacteria. As a result of adaptations to
variable ocean microenvironments, the genomes of marine
bacteria indicate a plethora of yet-to-be-discovered secondary
metabolites. This is a frontier field in natural products. Our
laboratory has studied the siderophores produced by the
marine actinomycete Salinispora tropica CNB-440, and shown
that this species produces a number of different linear and
macrocyclic siderophores (Figure at right). In this project, you will undertake an approach designed to
significantly increase the number of siderophores biosynthesized by this species – we aim to break the
record for the number of siderophores able to be characterised from a single species.
TECHNIQUES
Microbiology, LC-MS, Coordination chemistry, Analytical biochemistry
Selected publications
[1] Codd, R. (2008). Traversing the coordination chemistry and chemical biology of hydroxamic acids, Coord. Chem.
Rev., 252, 1387-1408.
[2] Telfer, T. J.; Gotsbacher, M. P.; Soe, C. Z.; Codd, R. (2016). Mixing up the pieces of the desferrioxamine B jigsaw
defines the biosynthetic sequence catalyzed by DesD, ACS Chem. Biol., 11, 1452-1462.
[3] Ejje, N.; Soe, C. Z.; Gu, J.; Codd, R. (2013). The variable hydroxamic acid siderophore metabolome of the marine
actinomycete Salinispora tropica CNB-440, Metallomics, 5, 1519-1528.
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Dr Tina HINTON
Biomedical Sciences Education
Rm 2N12, Charles Perkins Centre
[email protected]
Pharmacology is a biomedical science taught to numerous cohorts
(science, medicine, pharmacy, nursing) requiring different
applications of the discipline skills and knowledge. Research projects
to date have included national and multidisciplinary teams
evaluating pharmacology curriculum across degree programs, student
experience of specific learning activities, student engagement and
student learning, and impact of changes to curriculum on skills
development and learning outcomes. A number of projects are
currently underway in the area of innovative learning spaces. This
research forms part of the Centre for Research in Learning and
Innovation and the Charles Perkins Centre Science of Learning
Science Research Node.
Co-supervisors: Professor Philip Poronnik (Physiology), Professor Peter
Goodyear (Education)
Research interests & publications:
http://sydney.edu.au/medicine/people/academics/profiles/tinah.php
Research group (2016):
http://sydney.edu.au/medicine/people/academics/publications/tinah.php
PROJECT 1
IMPACT OF LEARNING SPACE ON BIOMEDICAL SCIENCES LEARNING AND
TEACHING
Will suit a student with interests in field research methods, education and translation of
pharmacology skills and knowledge into education
The Charles Perkins Centre (CPC) encourages a new model for multi- and
transdisciplinary education and research. The new learning spaces within the CPC
building include large collaborative learning spaces, flexible learning spaces and a
learning studio, and custom-built learning spaces such as an exercise laboratory.
These spaces were designed to provide opportunities for teaching large groups,
with cohorts from different disciplines, years of candidature, units of study and
degree programs working side by side. This is a major departure from traditional
learning spaces and provides an unprecedented opportunity to evaluate the impact
of learning space on what and how we teach and learn in pharmacology and other
biomedical sciences. This project will form part of an investigation into student and
staff experiences of physical and social factors that influence learning and teaching,
as well as changes in learning and teaching practices and curriculum and
pedagogical design in new learning spaces. This project involves learning the skills
associated with qualitative and quantitative education research – designing and
analysing interviews and surveys as well as ethics and recruitment. The project
occurs in collaboration with Professor Philip Poronnik (Physiology) and Professor
Peter Goodyear (Education).
TECHNIQUES
Field research methods – questionnaire, interview, data analysis and statistics
12
Dr Slade MATTHEWS
PharmacoInformatics Laboratory
Room 349C, Blackburn Building
[email protected]
The PharmacoInformatics Laboratory uses computer technologies to uncover
new relationships in biomedical data. PharmacoInformatics incorporates the
principles of computerised data management, machine learning techniques
and complexity analysis in a pharmacology context. These techniques as well
as applied statistics are used on a range of problems in this lab including
clinical observational studies and laboratory based data driven studies.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/sladem.php
Research group (2016)
Davy Guan (PhD student), Yuhanif Yusof (Post Doc), Zuriyat Iqbal (MD student),
Peter Wang (MD student), Dargos Stefanescu (MD student), Hamish Carmichael
(MD student)
PROJECT 1
IN SILICO TOXICOLOGY MODELLING
The prediction of toxicity is an important part of the assessment of drugs in
development. The cost associated with detection of drug toxicity late in drug
development is enormous and so it has become important to develop in silico
models of toxicity to detect toxic effects early. In silico toxicology is essentially
similar to QSAR but considers combinations of a greater number of parameters for
making toxicity predictions. Computational models are also useful when
considering drug impurities and theoretical impurities that may not be sufficiently
abundant to be fully tested in vivio. This project aims to generate a model of fatal
toxicity of antidepressants and/or sedative hypnotics using the fatal toxicity
index (FTI) and a range of databases and several in silico toxicology and chemistry
programs. Sodium channel binding and offset kinetics and physicochemical
properties will be used to characterise these drugs.
Students will be co-supervised by Professor Nick Buckley
TECHNIQUES
The techniques employed include: use of computational toxicology softwares; searching
and researching databases including PubChem, TGA, PubMed, interpretation In Silico
toxicological relationships.
PROJECT 2
Hand cream interference with Blood glucose monitoring
Blood glucose monitoring is essential for patient care in type 1 and 2 diabetic
patients. The importance of accurate blood glucose (Bgl) measurement is
paramount but there are several conditions which affect the accuracy of these
devices including temperature, altitude, and substances on the skin. There are
several types of monitors that contain different enzyme systems and the
substances that interfere with the results may vary. In this project you will
investigate the level of interference caused by dermally applied substances
including cosmetics and medicines. The results will inform correct use of the
monitors and lead to higher quality diabetic patient care.
Students will be co-supervised by Professor Nick Buckley
TECHNIQUES
BGl monitoring, Experiments with humans
RECENT PUBLICATIONS:
1. Ebach, M., Michael, M., Shaw, W., Goff, J., Murphy, D., Matthews, S. (2016). Big data and the historical
sciences: A critique. Geoforum, 71, 1-4
2. Dixit, R., Matthews, S., Khandaker, G., Walker, K., Festa, M., & Booy, R. (2016). Pharmacokinetics of
oseltamivir in infants under the age of 1 year. Clin Transl Med, 5(1), 37.
3. Gnjidic, D., Bennett, A., Le Couteur, D., Blyth, F., Cumming, R., Waite, L., Handelsman, D., Naganathan,
V., Matthews, S., Hilmer, S. (2015). Ischemic heart disease, prescription of optimal medical therapy and
geriatric syndromes in community-dwelling older men: A population-based study. International Journal of
Cardiology, 192, 49-55.
4. Marzbanrad, F., Khandoker, A., Hambly, B., Ng, E., Tamayo, M., Lu, Y., Matthews, S., Karmakar, C.,
Palaniswami, M., Jelinek, H., et al (2016). Methodological Comparisons of Heart Rate Variability Analysis in
Patients With Type 2 Diabetes and Angiotensin Converting Enzyme Polymorphism. IEEE Journal of Biomedical
and Health Informatics, 20(1), 55-63.
13
Prof Michael MURRAY
Cancer Pharmacogenomics and Drug Development
Level 1, Medical Foundation Building
[email protected]
Projects in the Pharmacogenomics and Drug Development Group take a
multidisciplinary approach to problems in cancer chemotherapy. Our
current focus is on the development of new anti-cancer drugs, and on
anticancer drug resistance, which leads to tumours that are untreatable
with the available drugs. We use a combination of molecular
pharmacology, cell biology, synthetic chemistry and in vivo preclinical
models in these projects. Our aim is to develop effective new drugs that
treat cancers by new mechanisms and to use pharmacogenomics to assist
drug selection in cancer.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/mmur2743.php
Research group (2016):
Sarah Allison, Yong Chen (postdocs), Kirsi Bourget (Res Asst), Nooshin Koolaji,
Hassan Choucair, Yassir Al-Zubaidi, Md Khalilur Rahman(postgrads), Bala
Umashankar (Hons)
PROJECT 1
New anticancer drugs that target tumour cell mitochondria
The treatment of advanced breast cancer often fails due to limited choices
of drugs for therapy. New molecules that act by different mechanisms are
needed to provide additional therapeutic options. We have designed a new
class of anti-cancer agents that act like ω-3 fatty acid metabolites that are
formed in cells. These agents rapidly kill breast cancer cells in vitro and in
vivo in nude mice carrying xenografted tumours. Identifying how these
agents kill cancer cells will provide new drug targets for the rational design
of next generation anti-cancer drugs.
TECHNIQUES
cell culture, immunoblotting, real-time PCR, medicinal chemistry, cell-based assays
PROJECT 2
Novel anti-metastatic agents based on ω-3 fatty acid metabolites
Metastasis is the major life-threatening consequence of malignant tumours.
At present there are no effective drugs to prevent metastasis. In our current
work we have designed a new class of anti-metastatic agents that inhibit
the growth and migration capacity of highly aggressive breast and prostate
tumour cells in vitro and in vivo. Understanding how these agents prevent
tumour cell migration will enable the synthesis of optimal anti-metastatic
agents to treat advanced cancers.
TECHNIQUES
Tumour cell migration assay
cell culture, RNA-seq, proteomics, immunoblotting, real-time PCR, cell-based assays
Selected publications
1. M Murray, A Hraiki, M Bebawy, C Pazderka and T Rawling. Anti-tumor activities of lipids and lipid analogues and their development
as potential anticancer drugs. Pharmacol Ther 150, 109-128 (2015).
2. SE Allison, N Petrovic, PI Mackenzie and M Murray. Pro-migratory actions of the prostacyclin receptor in human breast cancer cells
that over-express cyclooxygenase-2. Biochem Pharmacol 96, 306-314 (2015).
3. HRE Dyari, T Rawling, K Bourget and M Murray. Synthetic ω-3 epoxyfatty acids as anti-proliferative and pro-apoptotic agents in
human breast cancer cells. J Med Chem 57, 7459-7464 (2014)
4. M Murray, HRE Dyari, SE Allison and T Rawling. Lipid analogues as potential drugs for the regulation of mitochondrial cell death.
Brit J Pharmacol (Themed Issue: Mitochondrial Pharmacology - Energy, Injury & Beyond) 171, 2051-2066 (2014).
5. PH Cui, T Rawling, K Bourget, T Kim, CC Duke, MR Doddareddy, DE Hibbs, F Zhou, BN Tattam, N Petrovic and M Murray.
Antiproliferative and antimigratory actions of synthetic long chain n-3 monounsaturated fatty acids in breast cancer cells that
overexpress cyclooxygenase-2. J Med Chem 55, 7163-7172 (2012).
14
A/Prof Renae RYAN
Transporter Biology Group
Room 211, Blackburn Building
[email protected]
The Transporter Biology Group investigates the molecular mechanisms of
neurotransmitter and amino acid transporters. The aim of our research is
to develop a structural model for how these transporters work, and in this
way lay the foundations for a more rational approach to the development
of drugs that are both transporter-specific and subtype selective and can
be used to treat neurodegenerative disorders, schizophrenia, chronic pain
and cancer.
Research interests & publications:
http://sydney.edu.au/medicine/people/academics/profiles/renaer.php
Research group (2016):
Prof Rob Vandenberg, Dr Josep Font, Rosemary Cater, Shannon Mostyn, Natasha
Freidman, Qianyi Wu, Emily Crisafulli, Cheryl Handford
PROJECT 1
Developing novel cancer therapeutics that inhibit glutamine transport
The glutamate transporter family (SLC1 family) is made up of proteins from several species and includes the
human glutamate transporters (EAATs) and neutral amino acid transporters (ASCTs), and a prokaryotic
aspartate transporter (GltPh) which is a structural model of the SLC1 family. We have used the similarities
and differences between these family members to better understand the molecular
basis for their specific functions and have used this information to develop novel
compounds to selectivity target ASCT2.
Cancer cells rely heavily on the import of the amino acid glutamine to fuel their
excessive growth and proliferation. ASCT2 is a glutamine transporter that is known
to be upregulated in several types of cancer including breast cancer, prostate
cancer and melanoma and ASCT2 is the primary route for glutamine entry into these
cancer cells. Our group is currently developing novel selective and potent ASCT2
inhibitors that will hopefully lead to a new class of cancer therapeutics. This project
will focus on characterising several novel compounds that have been developed to
selectively target ASCT2. The results of this project will further inform drug design
to develop potent and selective ASCT2 inhibitors as novel cancer therapeutics.
PROJECT 2
Investigating the elevator mechanism of the glutamate transporters
In addition to their primary role of clearing glutamate from the synapse, the human glutamate transporters
(aka the EAATs) allow the flux of chloride across the membrane. Work in our group is focused on
understanding the molecular basis for these dual mechanisms and their role in physiology. We have already
identified two distinct pathways through the transporter for glutamate and chloride and have shown that
activation of the chloride conductance is linked to the elevator mechanism that is required for glutamate
transport. The aim of this project is to further examine this newly identified region of the transporter to
gain more information about how these proteins carry out these dual functions.
TECHNIQUES
molecular biology (including site-directed mutagenesis); electrophysiology; protein
purification; liposome reconstitution; radiolabelled uptake; x-ray crystallography
molecular modelling; drug design
Glutamate transporter dysfunction has been implicated in disease states such as ischemia following a stroke,
Alzheimer’s disease and obsessive compulsive disorder and the expression of ASCT2 is known to be
upregulated in several cancers including prostate, breast and skin cancer. Through a better understanding
of the mechanism of these transporters we can develop novel therapies to treat these disease states.
Selected publications
[1] Cater, RJ, Vandenberg, RJ and Ryan RM (2016) Tuning the ion selectivity of glutamate transporter–associated uncoupled
conductances. The Journal of General Physiology 148, 13-24.
[2] Ryan RM and Vandenberg RJ (2016) Elevating the alternating-access model. Nature Structural & Molecular Biology 23, 187-189.
[3] Scopelliti AJ, Ryan RM and Vandenberg RJ (2013) Molecular Determinants for Functional Differences between Alanine-SerineCysteine Transporter 1 and other Glutamate Transporter Family Members. The Journal of Biological Chemistry 288, 8250-7
[4] Qian Wang, … Josep Font, …. Renae M Ryan, Mika Jormakka, Nikolas K. Haass, John E. J. Rasko, Jeff Holst (2014) Targeting
glutamine transport to suppress melanoma cell growth. International Journal of Cancer
[5] Boudker O, Ryan RM, Yernool D, Shimamoto, K and Gouaux E (2007) Coupling substrate and ion binding to extracellular gate of a
sodium-dependent aspartate transporter. Nature 445, 387-393.
15
A/Prof Margie SUNDE
Functional Amyloid Biology Group
Room 214, Blackburn Building
[email protected]
The formation of stable thread-like protein assemblies known as amyloid
fibrils is associated with many human diseases. However, functional amyloid
protein fibrils with similar structural features have recently been identified in
mammals and many different microorganisms. These amyloid fibrils perform a
wide range of functional roles and are advantageous to the organisms. The
Sunde lab uses molecular biology, protein chemistry, fluorescence and
structural techniques to study the formation of functional amyloid fibrils
associated with microbial infections and cell death by necroptosis [1].
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/msunde.php
Research group (2017):
1 postdoctoral researcher, 2 PhD students, 1 research assistant
PROJECT 1
THE ROLE OF FUNCTIONAL AMYLOID FIBRILS IN FUNGAL INFECTIONS
Will suit a student with interests in protein self-assembly and antimicrobials
Fungi produce amyloid fibrils that are composed of hydrophobin proteins [2].
These fibrils form a protective coating on fungal spores and facilitate infection
of human, animal and plant hosts. Fungal infection of rice by the fungus
Magnaporthe oryzae causes loss of up to a third of the annual global rice
harvest. The protein MPG1 forms fibrils on the surface of M. oryzae spores and
assists in attachment to rice leaves and infection. You will express MPG1 and a
number of mutant forms of this protein recombinantly in bacteria. You will
purify these proteins and study the process of the formation of amyloid fibrils
by the hydrophobin MPG1 and mutants. In this way you will identify the
important regions of MPG1 that control formation of amyloid fibrils and
Atomic force micrograph
provide structural stability to the hydrophobin layer. You will study the effect
showing amyloid fibrils formed
of chemical chaperones on the process of hydrophobin amyloid formation with
by the hydrophobin MPG1.
a view to identifying small molecules that could inhibit the formation of this
protective protein coat. This could have broad application in treatment of
human, animal and plant infections caused by hydrophobin-secreting fungi.
TECHNIQUES
Molecular biology, protein expression and purification, fibril formation assays,
fluorescence studies, fibril inhibition and disassembly experiments.
PROJECT 2
FUNCTIONAL AMYLOID COMPLEXES IN REGULATED CELL DEATH
Will suit a student with interests in cell biology and protein:protein interactions
Amyloid-stabilised assemblies
formed by the RHIM domain of
RIPK1 kinase.
TECHNIQUES
The formation of functional amyloid complexes in human cells is associated with
the induction of cell death in response to microbial infection and in other
inflammatory conditions. Li et al. (Cell (2012) 150: 339-50) demonstrated that
this involved amyloid fibril formation by the RIPK1 and RIPK3 protein kinases.
These kinases contain amyloid-forming RHIM domains. Two other human
proteins associated with the host response to microbial infections, ZBP1 and
TRIF, also contain RHIM domains. We hypothesize that these proteins form
amyloid fibril complexes with RIPK1 and RIPK3 to signal for cell death by the
regulated pathway to cell death known as necroptosis. You will express the
RHIM domains of human RIPK1, RIPK3, ZBP1 and TRIF and will study amyloid
formation by these domains. You will investigate whether ZBP1 and TRIF can
form functional amyloid complexes with human RIPK1 and RIPK3 kinases. You
will use site-directed mutagenesis to identify the key residues in these proteins
that are required for amyloid fibril formation.
Molecular biology, protein expression and purification, fibril formation assays,
protein:protein interaction studies.
Selected publications
[1] Pham, C. L., Kwan, A. H. & Sunde, M. Functional amyloid: widespread in Nature, diverse in purpose. Essays in Biochemistry
(2014) 56, 207-219.
[2] Pham, C. L. et al. (2016) Self-assembly of MPG1, a hydrophobin protein from the rice blast fungus that forms functional amyloid
coatings, occurs by a surface-driven mechanism. Scientific Reports, 6, 1-16.
16
Prof Daniela Traini - ARC Future Fellow
Respiratory Technology
The Woolcock Institute of Medical Research-Glebe
[email protected]
Dr Traini’s research explores respiratory drug delivery science. It
focuses on understanding the physical properties of materials used in
pharmaceutical sciences and then in relating those to in-vitro and
subsequent in-vivo performance. She has expertise in projects related
to asthma, chronic obstructive pulmonary diseases and bronchiectasis.
High-end imaging is also one of her interests. She is currently working
toward understanding the co-formulation and co-deposition of
inhalation active pharmaceutical ingredients to enhance their
synergistic therapeutic effect.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/danielat.phd
Research group (2016):
http://www.respitech.org
PROJECT 1
Formulationing antifungal lung delivery
Pulmonary infections caused by Aspergillus species are associated
with significant morbidity and mortality in immunocompromised
patients. Although the treatment of pulmonary fungal infections
requires the use of systemic agents, aerosolized delivery is an
attractive option in prevention because the drug can concentrate
locally at the site of infection with minimal systemic exposure.
Currently there are no treatment available, thus there is a need for
additional treatments. In this project we will reformulate antifungal
drug, as mono o combined formulation, to be delivered directly to the
lungs. Once formulated, we will analyse its performance and physicochemical characterises by a number of state of the art analytical
methods for aerosol performance. Furthermore, their toxicity and
transport on calu-3 cells grown in the air interface model will be also
investigated.
TECHNIQUES
Calu-3; Drug transport; Spray drying; Dissolution testing; HPLC
Co-supervisors: Prof Young, Dr Ong
PROJECT 2
Treating acute bronchiolitis
Bronchiolitis is an acute inflammatory injury of the bronchioles that is
usually caused by a viral infection. A combination of oral high dose
antibiotics and inhaled long-acting beta agonists (LABAs) are used for its
treatment. In this project we will develop a novel inhalable
combination formulation of an antibiotic i.e. amoxicillin and a LABA i.e.
Salmeterol, to avoid problems associate with high oral doses, variable
bioavailability and increase side effect effects. Once the microparticles
will be produced these will be analysed by a number of state of the art
analytical methods i.e. Light Scattering, Scanning Electron Microscope
and X-Ray Powder Diffraction. Aerosol performance and Chemical
stability will be also investigated
Figure 1: Schematic of Spray Dryer
apparatus
TECHNIQUES
Particle size, Spray drying; Dissolution testing; HPLC
Co-supervisors: Prof Young, Dr Ong
Selected publications
Haghi , M., Ong, HX., Traini, D., Young, PM. (2014) Across the pulmonary epithelial barrier: integration of physicochemical
properties and human cell models to study pulmonary drug formulations. Pharmacology & Therapeutics 144, 235–252
Arora, S.,Haghi, M., Loo, CY., Traini, D., Young, PM., Jain, S. (2015) Development of an Inhaled Controlled Release Voriconazole Dry
Powder Formulation for the Treatment of Respiratory Fungal Infection Mol. Pharmaceutics, 2015, 12 (6), pp 2001–2009
17
Prof Robert VANDENBERG
Transporter Biology Group
Room 210, Blackburn Building
[email protected]
Research in the Transporter Biology Group is focused on understanding the
molecular basis for neurotransmitter transporter functions and how this can
be manipulated by endogenous regulators and pharmacological agents. The
glycine transporter, GlyT2, is a promising target for the development of
novel analgesics for the treatment of neuropathic pain. Our group has
generated a series of potent lipid-based inhibitors of GlyT2 and we are
interested in understanding their mechanism of inhibition.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/robv.php
Research group (2016):
Co-group leader A/Prof Renae Ryan, Postdoc Dr Pep Font, PhD students
Shannon Mostyn, Rosie Cater, Diba Sheipouri. Honours students Emily Crisafuli,
Natasha Freedman, Qianyi Wu, Lab Manager Cheryl Handford
PROJECT 1
Allosteric Inhibitors of GlyT2
Will suit a student with interests in pharmacology/biochemistry/neuroscience/physiology
Glycine transport by GlyT2 can be allosterically inhibited by a range
of compounds, some of which show promise as analgesics for the
treatment of chronic pain. In this project you will form part of a
multidisciplinary group that is working towards the development of
novel drugs for the treatment of pain. N-arachidonyl-glycine is an
endogenous lipid inhibitor of GlyT2, but there is little understanding
Potential
of how it interacts with the transporter. In this project you will
Lipid
investigate how this and related compounds interact with GlyT2 and
Binding
then use this information to develop potent and selective GlyT2
inhibitors (see figure). A number of research directions and
Site
techniques are possible with this project. Students are encouraged to
discuss the project with Professor Vandenberg so that the style of the
project can be tailored to the student’s interests. Techniques to be
used included recombinant DNA techniques such as site-directed
mutagenesis, DNA/RNA synthesis, electrophysiology, computer
simulations of protein structure and function. Work on this project is
supported by a Project Grant from the NHMRC.
TECHNIQUES
Molecular biology, site-directed mutagenesis, electrophysiology, molecular modelling
Selected publications
1. Robert J. Vandenberg, Renae M. Ryan, Jane E. Carland, Wendy L. Imlach, and Macdonald J. Christie (2014) Glycine transport
inhibitors for the treatment of pain Trends in Pharmacological Sciences 35, 423-430
2. Jane E Carland, Cheryl A Handford, Renae M Ryan and Robert J Vandenberg (2014) Lipid Inhibitors of High Affinity Glycine
Transporters: Identification of a novel class of analgesics. Neurochemistry International 73, 211-216
3. Jane E Carland, Robyn Mansfield, Renae M. Ryan and Robert J Vandenberg (2013) Oleoyl-L-Carnitine Inhibits Glycine Transport by
GlyT2 British Journal of Pharmacology 168, 891-902
4. Amelia Edington, Audra McKinzie, Aaron J. Reynolds, Michael Kassiou, Renae M. Ryan and Robert J. Vandenberg (2009) Extracellular
Loops 2 and 4 of GLYT2 are Required for NAGly Inhibition of Glycine Transport Journal of Biological Chemistry 284:36424-36430.
18
Prof Paul Young
ARC Future Fellow, Head of Respiratory Technology
Woolcock Institute of Medical Research
[email protected]
My research group develops new approaches and tools to study and treat
respiratory diseases. We focus on developing new medical devices and
advanced formulations that can target specific regions of the lung.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/paulyoung.php
Research group (2015):
http://www.respitech.org
PROJECT 1
Development of a functioning tissue model of the respiratory tract
This project, co-supervised with Brent McParland will focus
on developing representative models of the lung epithelia
that incorporate cilia escalator and transport function. The
lung is a complex organ and the uptake and disposition of
drugs is dependent upon the properties of the epithelia
(including influx and efflux trans-membrane transporters,
mucus properties and cilia function) and the properties of
the drug molecule (such as ionisation and solubility
parameters). This project will establish a tissue model that
can be used to study the transport and clearance of drugs
after deposition at the interface. Based on a porcine model,
you will isolate tracheal tissue and study the expression of a
range of transport relating proteins, cilia function and mucus
properties. You will then utilise this model to investigate the
uptake properties of a range of pharmacologically relevant drug molecules.
TECHNIQUES
HPLC, PCR, Western blot, Drug delivery, microscopy
Co supervisors B McParland D Traini, H-X Ong
PROJECT 2
Developing new particulate systems to treat respiratory disease
Respiratory tract infection is the number 1 cause of communicable disease
worldwide. Currently treatment regimes involve ether oral delivery of
antibiotics or, when in intensive care, antibiotic intravenous injection. A
logical approach would be to deliver antibiotics by inhalation since this
would reduce the required dose and the potential for antibacterial
resistance. However, in order to achieve this the particles must have a
diameter < 5µm and have enhanced residency time at the epithelia. In
this project, you will gain experience in the area of particle engineering,
state-of-the-art physico-chemical characterisation and drug delivery. We
will design a novel inhaled antibiotic particle that has enhanced residence
in the lung through its interaction with the epithelia/surface lung fluid.
TECHNIQUES
Particle engineering, in vitro testing, HPLC, microscopy, colloid science
Co supervisor D Traini
Selected publications
Ong, H.X., Benaouda F., Traini, D., Cipolla, D., Gonda, I., Bebawy, M., Forbes, B., Young, P.M. In vitro and ex vivo
methods predict the enhanced lung residence time of liposomal ciprofloxacin formulations for nebulisation. European
Journal of Pharmaceutics and Biopharmaceutics (Accepted June 23rd 2013).
Ong, H.X., Traini, D., Young, P.M. Pharmaceutical Applications of the Calu-3 lung epithelia cell line. Expert Opinion
on Drug Delivery. (Accepted May 9th 2013).
Ong, H.X., Traini, D., Bebawy, M., Young, P.M. (2013) Ciprofloxacin is actively transported across bronchial lung
epithelial using a Calu-3 air-interface cell model. Antimicrobial Agents and Chemotherapy. Vol 57, 2535-2540.
Mamlouk, M., Young, P.M., Bebawy, B., Haghi, M., Mamlouk, S., Mulay, V., Traini, D. (2013) Salbutamol Sulphate
absorption across Calu-3 bronchial epithelia cell monolayer is inhibited in the presence of common anionic NSAIDs.
Journal of Asthma. Vol 50, 334-341.
19
Dr. Karin AUBREY ([email protected])
Pain Management Research Institute (Kolling Institute at
the Royal North Shore Hospital)
Information about pain is first processed in the dorsal horn of the spinal cord
and then sent to the brain by specialized ascending pain-pathways. Incoming
noxious signals are processed and modulated in the spinal cord by local circuits,
as well as by descending pathways from higher brain regions. The neurobiology
of pain research group examines spinal cord circuits in order to understand how
specific and nuanced pain signals are communicated and what happens to these
signals when chronic pain develops.
Research interests/publications:
PROJECT 1
http://sydney.edu.au/medicine/people/academics/profiles/karin.aubrey.php
Inhibitory Synapses of the Spinal Cord
Will suit a student with interests in pharmacology or
physiology
Two similar, but functionally distinct amino acid neurotransmitters
carry out fast inhibitory transmission in the spinal cord. The reason
two transmitters are required in this region is unclear. In this
project you will examine how the two inhibitory neurotransmitters
interact at the presynaptic terminal by recording synaptic currents
from pairs of connected spinal cord neurons in culture.
TECHNIQUES
Primary neuronal culture, electrophysiology, pharmacology, brain slice
PUBLICATIONS. Aubrey, K.R., Drew, G.M., Jeong, H., Lau, B.K., Vaughan, C.W. Endocannabinoids control vesicle release mode at
midbrain periaqueductal grey inhibitory synapses (2016) J. Physiol. (DOI 10.1113/JP272292); Aubrey K.R., Presynaptic control of
inhibitory neurotransmitter content in VIAAT containing synaptic vesicles (2016) Neurochem. Int. 98, pp. 94–102; Wang, L., Tu, P.,
Bonet, L., Aubrey, K.R., Supplisson, S. Cytosolic Transmitter Concentration Regulates Vesicle Cycling at Hippocampal GABAergic
Terminals (2013) Neuron, 80 (1), pp. 143-158.
Dr Chris VAUGHAN ([email protected])
Pain Management Research Institute
Kolling Institute at Royal North Shore Hospital
Our research group examines the mechanisms underlying chronic pain and is
identifying novel pain relieving drugs, particularly those related to
cannabinoids. This work is done using a range of behavioural and cellular
techniques.
Research interests & publications:
http://sydney.edu.au/medicine/people/academics/profiles/chris.vaughan.php
Research group (2016):
Dr Wayne Anderson, Dr Hyo-Jin Jeong, Dr Bryony Winters (Postdocs). Vanessa
Mitchell, Patrick Seow (Research Assistants). Sherelle Casey (PhD student).
Nicholas Atwal, Hannah Clements (Honours students).
PROJECT 1
Chronic Pain & Cannabinoids
Chronic pain syndromes particularly those caused by injury to the
nervous system (neuropathic pain) are often resistant to traditional
analgesics. The psychoactive ingredient of marijuana, THC, is
effective in alleviating these pain syndromes by acting on an
endogenous cannabinoid neurotransmitter system, however, its use
is limited by side-effects. This project will examine the pain relieving
actions and side-effects of other cannabis constituents activity in an
animal model of chronic pain1-3.
TECHNIQUES
Pain & behavioural testing. Animal recovery surgery. Electrophysiology.
RELEVANT PUBLICATIONS. [1] Kazantzis NP, Casey SL, Seow PW, Mitchell VA & Vaughan CW (2016) Opioid and cannabinoid synergy in
a mouse neuropathic pain model. Brit J Pharmacol 173:2521-31. [2] Adamson Barnes NS, Mitchell VA, Kazantzis NP & Vaughan CW
(2014) Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model. Neuropharmacology 81:224-30. [3] Lau
BK, Drew GM, Mitchell VA & Vaughan CW (2014) Endocannabinoid modulation by FAAH and MAGL within the analgesic circuitry of the
periaqueductal grey. Brit J Pharmacol 171:5225-36.
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A/Prof Kay DOUBLE ([email protected])
Neurodegenerative disorders (Brain & Mind Centre)
Our research focuses on developing pharmaceutical treatments for Parkinson’s
disease and amyotrophic lateral sclerosis, based around degenerative cascades
involving protein and metal changes in these disorders. Approaches include extensive
use of human CNS tissues, as well as animal modelling and clinical projects. Our
laboratory is based in the Brain and Mind Centre in Mallett St, Camperdown.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/kay.double.php
Research group (2016)
Research group of eight including 5 PhD and 1 Hons student.
PROJECT 1
COX AND MITOCHONDRIAL DYSFUNCTION IN PARKINSON’S DISEASE
Suits students with interests in wet lab-based research, neurodegenerative disease and human brain
Metals are key co-factors in a number of cell processes, including energy production
by mitochondria. In the neurodegenerative disorder Parkinson’s disease mitochondrial
function is thought to be impaired and contribute to degenerative processes. We
have recently shown that neuronal copper levels are markedly decreased in the
Parkinson’s disease brain and that this change is associated with reduced function of a
number of cellular copper-dependent processes. Within mitochondria, cytochrome c
oxidase (COX) is a copper-dependent enzyme in the electron transport chain but it is
unknown if the function of this critical cuproprotein is altered in the copper-deficient Parkinson’s disease brain
and, if so, the implications of this for neuron survival. In this project we will isolate mitochondria from
Parkinson’s disease and age-matched brains and investigate copper levels and levels and activity of COX in these
tissues. This project will have implications for planned clinical trials which aim to restore brain levels of copper,
and thus the function of copper-dependent proteins, in Parkinson’s disease.
TECHNIQUES
human tissue preparation, metal analyses using mass spectroscopy, immunoblotting, enzyme
activity assays
Selected publications: [1] Davies, K.M., et al & Double, K.L. (2015) Copper dyshomeostasis in Parkinson’s disease: Implications for
pathogenesis and indications for novel therapeutics. Clin. Sci. 130, 565-574. [2] Davies, K.M. et al & Double, K.L. (2014) Copper
pathology in vulnerable brain regions in Parkinson’s disease. Neurobiol Aging, 35, 858-866.
Prof Sarah HILMER ([email protected])
Ageing and Pharmacology (Kolling Building, RNSH)
Sarah Hilmer leads a translational geriatric pharmacology research group at the Kolling
Institute, Royal North Shore Hospital. We study pharmacology in ageing, aiming to
improve the safety and efficacy of medicines for older people. Using basic experimental
pharmacology in our novel pre-clinical models, we study the effects of polypharmacy and
deprescribing in old age. Our clinical pharmacology research investigates drug use,
pharmacokinetics, pharmacodynamics, safety and efficacy of drugs, alone and in
combinations, in fit and frail older people with and without dementia. Pharmacology
honours students are co-supervised by Dr Slade Matthews and Professor Peter Carroll.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/shilmer.php
Research group (2016)
Postdocs 3; Students 2 PhD, 1 Masters, 2 Honours; Research Pharmacist 1;
Research Assistants 2; International Fellow 1
PROJECT 1
UNDERSTANDING AND OPTIMISING THE EFFECTS OF POLYPHARMACY IN OLD AGE
Suits students with interests in pre-clinical or clinical research, prescribing practice and ageing
In old age, with an increase in multi-morbidity, comes an increase in polypharmacy (concurrent
use of ≥5 different medicines). We have developed a novel pre-clinical model of polypharmacy
to evaluate the effects of polypharmacy on physical and cognitive function in old age, and
whether the effects are reversible with medicines withdrawal (deprescribing). We are also
conducting clinical studies in the community and in hospital, investigating how to improve
medicines use by older people with and without dementia to optimise their independence.
Opportunities exist for an honours student to contribute to our pre-clinical or clinical research.
TECHNIQUES
Measuring physical and cognitive function and frailty, histopathology/immuno-histochemistry, LCMS,
data collection from patients and medical records, data analysis
Selected publications: Huizer-Pajkos A, Kane AE, Howlett SE, Mach J, Mitchell SJ, de Cabo R, Le Couteur DG, Hilmer SN. Adverse
Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The Influence of Aging. J Gerontol A Biol Sci (2016) 71:571-7
Kouladjian L, Gnjidic D, Chen TF, Mangoni AA, Hilmer SN. Drug Burden Index in older adults: theoretical and practical issues. Clin
Interv Aging (2014) 9:1503-15.
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Prof Michael KASSIOU ([email protected])
Drug Discovery Research Unit (Rm 465, Blackburn Building)
Drug discovery research within my group is multidisciplinary and at the interface
between chemistry and biology. The research is primarily concerned with the
understanding of drug-protein and drug-binding site interactions in order to
obtain structure-activity relationships of bioactive CNS molecules. This allows the
rational design of more efficacious treatments for diseases of the brain.
Research interests/publications:
http://sydney.edu.au/medicine/people/academics/profiles/mkassiou.php
Research group (2016):
Dr Eryn Werry (Post-doc), Ms Miral Mikhail (PhD Student), Mr Alex Jackson (PhD
Student), Mr Erick Wong (PhD Student), Mr Damien Gulliver (PhD Student)
Ms Sophie Vo (Honours Student), Ms Helen Clunas (Masters Student), Mrs Kata
Popovic (Research Assistant)
PROJECT 1
THE ROLE OF TRANSLOCATOR PROTEIN POLYMORPHISM IN DRUG DISCOVERY
The translocator protein (TSPO) in the outer mitochondrial
membrane is a novel target for development of anxiolytics,
anti-cancer drugs and diagnostic imaging agents. A recent
phase II clinical trial of a TSPO ligand in general anxiety
disorder failed due to the presence of a common TSPO
polymorphism (Ala147Thr) at which the ligand lost activity.
Our group has developed novel TSPO ligands hypothesised to
interact effectively with Ala147Thr TSPO. This project will
involve characterising the ability of these ligands to bind to
and activate both wild type and Ala147Thr TSPO to identify
a novel candidate to progress through further stages of drug
discovery.
TECHNIQUES
Cell culture, radioligand binding, cellular assays
PROJECT 2
DRUG DISCOVERY FOR NEUROINFLAMMATION
Microglia are the resident immune cells of the central
nervous system. They carry out a wealth of helpful
neuroprotective functions, including refining neural
networks, phagocytosis of harmful molecules like β-amyloid
and release of anti-inflammatory mediators. Threatening
stimuli, however, can trigger the transformation of microglia
into a pro-inflammatory state that can damage cells and
even cause accumulation of β-amyloid. Recently, it has been
shown that transforming microglia from the proinflammatory to the neuroprotective state is sufficient to
reverse the pathological features and cognitive symptoms of
a mouse model of Alzheimer’s disease1. The aim of this honours project is to develop a brain-permeant
molecule that can drive pro-inflammatory microglia into the neuroprotective form. It is hoped that this
molecule can then be progressed into preclinical trials in neuroinflammatory disease models, such as
Alzheimer’s disease.
References: 1. P.N.A.S (2016) 113:E2705-2713
TECHNIQUES
Cell culture, cellular assays, immunofluorescence
PUBLICATIONS. (1) Werry EL, Barron ML, Kassiou M (2015) TSPO as a target for glioblastoma therapeutics Biochem. Soc. Trans. 43:531536 (2) Scarf AM, Kassiou M (2011) The translocator protein J Nuc. Med. 52:677 (3) Scarf AM, Ittner LM, Kassiou M (2009) The
translocator protein (18 kDa): Central nervous system disease and drug design. J. Med. Chem. 52:581-592.
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Where are they now?
Honours is a fantastic year in itself, but is also a springboard to postgraduate studies and careers in
industry and government. Shown in the Table below are the current positions of a selection of students
who have completed Honours or a Graduate Diploma in Pharmacology.
Name
Completed
Current Position
Phuoc Huynh
2010
PhD Candidate (Pharmacology, University of Sydney)
Carleen Fernandez
2010
PhD Candidate (Centenary Institute)
Vivian Liao
2010
PhD Candidate (Pharmacy, University of Sydney)
Dmitry Goloskokov
2010
Laboratory Aide (Douglass Hanly Moir Pathology)
Lauren Brites
2009
Research Assistant (EnGeneIC)
Sai Krishnan
2009
PhD Candidate (Children’s Medical Research Institute)
Marietta Salim
2009
Research Assistant (Transporter Biology Group)
Areeg Hamdi
2009
Masters Candidate (Pharmacy, University of Sydney)
Steven Devenish
2008
PhD Candidate (Pharmacy, University of Sydney)
Nicholas Kortt
2008
Medicine (University of Notre Dame)
Phoebe Hone
2008
Research Assistant (Veterinary Science)
Cho Zin Soe
2007
PhD Candidate (Pharmacology, University of Sydney)
Jonathon Tobin
2007
Medicine (University of Wollongong)
Jessica Kermale
2007
PhD Candidate (Woolcock Institute of Medical Research)
Amelia Eddington
2007
PhD Candidate (Pharmacology, University of Sydney)
Alana Scarf
2007
PhD Candidate (Brain & Mind Research Institute)
Chiu Chin Ng
2006
PhD Candidate (Pharmacology, University of Sydney)
Tim Bakas
2006
MPhil Candidate (Pharmacology, University of Sydney)
Brina Sheriff
2005
Poisons Information Centre
Nathan Gunasekaran
2005
PhD (University of Sydney), Medicine (University of Notre
Dame)
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Discipline of Pharmacology: Honours Preference Form (2017)
This form must be submitted to the Honours Coordinator by: Friday 18 November 2016.
An application for Honours must be lodged on line through the Faculty of Science.
I wish to apply for the following course in 2017 (circle choice):
BSc (Hons)
BSc Adv (Hons)
BMedSc (Hons)
Graduate Diploma
I intend starting my studies in (circle choice): Semester 1 or Semester 2.
STUDENT DETAILS:
First Name
Family Name
SID
E-mail (University of
Sydney Account)
Postal address
Phone (home)
Phone (mobile)
STUDENT PREFERENCES:
Please list your preferences for an Honours supervisor (from 1st to 4th preference). You must provide 4
names.
1
2
3
4
STUDENT TRANSCRIPT:
Please attach your academic transcript (photocopy or original) to this application.
Return to: A/Prof Rachel Codd, Room 274 Blackburn Building (D06)
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