2007
Chair of WHO Global ACHR reappointed
• Director of JCSMR, Professor Judith Whitworth was reappointed
Chair of the WHO Global Advisory Committee on
Health Research (ACHR).
Mathison Oration Medal
• Professor Judith Whitworth was invited to present the 23rd Mathison
Oration at The University of Melbourne, in
which she outlined some of the key health research discoveries of the
20th century.
Eccles Institute established
• During the year, JCSMR scientists were closely involved with
the establishment of the Eccles Institute of
Neuroscience, an ANU campus-wide virtual neuroscience consortium.
Frank Fenner retirement conference
• In November, the 12th Frank and Bobbie Fenner Conference celebrated
the life, work and retirement of Emeritus
Professor Frank Fenner. Professor Fenner was appointed Professor
of Microbiology at JCSMR in 1949. He was
Director of the School from 1967 to 1973, during which time he was also
Chairman of the Global Commission for
the Certification of the Eradication of Smallpox. The conference was
attended by many of Professor Fenner’s former
colleagues, including Nobel
Laureates Professor Peter Doherty and Professor Rolf Zinkernagel.
Understanding the ageing process
• Professor
Chris Goodnow and his Oxford University collaborator Professor Richard
Cornall were able to demonstrate
that ageing results from progressive incorporation of DNA errors into
the body’s stem cells, causing these stem cells
to gradually lose their regenerative capacity. The study emerged from
the team’s discovery of a unique mouse model
for a human childhood disorder that causes stunted growth and defects
in the immune and blood systems.
Neuroscience research receives a boost
• Research in the Division
of Neuroscience will be significantly boosted by the purchase of
a $300,000 long
wavelength ‘pulsed’ laser for a new two-photon facility
for both in vitro and in vivo live cell imaging.
Investigation of genetic mechanisms regulating immunity
• JCSMR investigators Professor
Chris Goodnow, Dr
Carola Vinuesa, Dr Edward Bertram and Associate
Professor Guna Karupiah
received major five year international grants from the Wellcome Trust
and the National Institutes of Health to lead
international consortia revealing new mechanisms and genes regulating
immunity to infection and autoimmunity.
They will employ strategies for genetic analysis of the immune system
pioneered at JCSMR in the last 10 years.
National Centre for Biosecurity expands
• The National Centre
for Biosecurity, led by JCSMR researcher Professor Ian Ramshaw,
and administered in collaboration
with University of NSW, expanded to include 45 members.
Ramaciotti Major Research Award
• In November, Dr Anselm Enders and Professor
Chris Goodnow won a Ramaciotti Foundation Major Research Award of
$1M
to establish a new Ramaciotti Immunisation Genomics Laboratory which
will research genetic issues around vaccines.
JDRF Special Program Grant
• Professor Christopher
Parish and his JCSMR Colleagues Dr Charmaine Simeonovic, Dr Gerard
Hoyne, Dr Craig Freeman
and Dr Sudha Rao were awarded a $3M Special Program Grant from the Juvenile
Diabetes Research Foundation and
the NHMRC. This five year award enables a new line of research into
the cause and possible treatment of diabetes.
Curtin Medal
• The Curtin Medal was presented to Professor Bruce Stillman.
Professor Stillman, who completed his PhD studies at
JCSMR in 1979, is currently the Director and President of the Cold Spring
Harbor Laboratory, New York, USA. His
research is focused on the mechanisms and regulation of DNA replication,
which is essential in ensuring
accurate inheritance of genetic material from one cell generation to
the next. The understanding of the DNA
replication process in healthy cells has been fundamental to his subsequent
studies on how the process goes awry
in cancer cells.
Arthur E Mills Memorial Oration Medal
• Professor Judith Whitworth received the Arthur E Mills Memorial
Oration Medal from The Royal Australasian College
of Physicians.
Finkel Prize
• The Alan and Elizabeth Finkel Prize was presented to Dr
Charani Ranasinghe for her work on a mucosal HIV AIDs
vaccine. This biennial prize acknowledges research which is relevant
to health in developing countries.
Professor Ada honoured
• Professor Gordon Ada’s many contributions to JCSMR
were honoured through the naming of the new Gordon Ada
Videoconferencing Room in Stage I of the new building.
Rowley Medal and Burnet Oration
• Professor Chris
Parish’s outstanding achievements and contributions in the
field of immunology were recognised by
the award of the 2007 Rowley Medal and the 2007 Burnet Oration by the
Australasian Society for Immunology.
Young Tall Poppy Award
• Dr Carola de Vinuesa received a NSW/ACT Young Tall Poppy award
from the Australian Institute of Policy and Science,
and the Biogen Spain International Prize for young scientists.
2006
Curtin Medal
• The Curtin Medal was presented to Professor Samuel Berkovic,
Head of the Comprehensive Epilepsy Program at the Austin Hospital and
the Epilepsy
Research Centre of the University of Melbourne. Professor Berkovic seeks
to understand the basic neurobiology of human epilepsies, using varied
approaches to gain insights that can be used for diagnosis and treatment
of patients. This research has pioneered understanding of the genetic
bases for epilepsy.
Proctor Medal
• Professor
Trevor Lamb (Division of Neuroscience) and his colleague Professor
Ed Pugh (University of Pennsylvania)were awarded the Proctor Medal of
the Association for Research in Vision and Ophthalmology (ARVO). The
Proctor Medal is presented annually for outstanding research in the
basic or clinical sciences asapplied to ophthalmology.
Federation Fellowship
• Professor Christopher Goodnow (Division of Immunology and Genetics)
was awarded an ARC Federation Fellowship. Professor Goodnow, Head
of the
Immunogenomics Laboratory at The John Curtin School of Medical Research
and Director of the Australian Phenomics Facility, will build an international
Immunity and Infection Genomics Consortium centred in Australia to tackle
three fundamental questions about the mammalian immune system: how
does the system learn not to attack self-components, how does it enhance
recall responses to vaccines, and why does it fail to eliminate formidable
foreign microbes?
Graduation success
• We congratulate the 15 PhD and 14 Honours students who successfully
completed their studies in The John Curtin School of Medical Research
during 2006.
Liver cancer trials to begin
• The anti-cancer therapeutic agent PI-88 developed within the
JCSMR laboratory of Professor
Chris Parish (Division of Immunology and Genetics) has shown promising
results in Phase II trials, and will now move into Phase III trials
as a treatment for liver cancer.
National Centre for Biosecurity announced
• ANU Vice Chancellor, Professor Ian Chubb announced the creation
of a new National Centre for Biosecurity.
Led by JCSMR immunologist
Professor Ian Ramshaw, the Centre brings together microbiologists, epidemiologists,
lawyers, ethicists, security analysts, infectious disease
modellers, policy experts, and integration and implementation scientists.
The Centre will take a ‘real world’ approach to the complex
problems of biosecurity and provide an essential link between the many
relevant disciplines.
ANU College of Medicine and Health Sciences
• During 2006, JCSMR joined the ANU College of Medicine and Health
Sciences. A number of JCSMR administrative staff transferred into the
newly formed College Administrative Group (CAG) and continue to provide
high quality administrative support.
2005
Professor Chris Parish
Cancer and
Vascular Biology Group
-
The cancer therapeutic PI-88, the breakthrough treatment
developed in the laboratory of Professor Christopher Parish and his
team in the Division of Immunology and Genetics has gone into expanded
clinical trials. Six hundred and fifty patients with primary liver
cancer, and advanced melanoma, lung and prostate cancer will be included
in the Phase II trials currently underway
-
Professor Trevor Lamb (Division of Neuroscience)
will Co-direct an ARC Centre of Excellence in Vision Science at The
Australian National University. This centre, funded by the ARC, will
work to provide a deeper understanding of the ways in which the visual
system functions, how it extracts information about the world, and
why it is that the eye is susceptible to degeneration
- A research team led by Dr Carola Garcia de Vinuesa (Division of Immunology
and Genetics) has discovered a new gene thought to contribute to autoimmune
diseases such as Type 1 diabetes and lupus. The gene, which they have
named Roquin, causes the body’s infection fighters, T cells, to
attack their own tissue. Potential treatments that target this mutation
will now be explored
Professor Judith Whitworth
High Blood Pressure Research Unit
Professor Paul Foster
Allergy and Inflammation Research Group
Professor Steve Redman and Dr Clarke Raymond
Movement
and Memory Laboratory
-
the discovery that spatial segregation of calcium
signals inside brain cells plays a powerful role in controlling the
strengthening of connections thought to underlie learning and memory
in the brain
-
Dr Bill Cowden
Immunopathology Group
Dr Bill Cowden’s group has challenged conventional dogma by
showing that in some autoimmune diseases, nitric oxide has a down-regulating
effect. Thus, in addition to having a localised tissue damaging role
in these diseases, it may, in contrast, actually slow down or reverse
the disease process. In the absence of nitric oxide production by
the immune system, some autoimmune diseases are actually more severe
and protracted than would otherwise be the case. This finding implies
that nitric oxide may 'feed-back' to signal the immune system to reduce
or halt its unwanted attack.
- Dr Charmaine Simeonovic
Diabetes/Transplantation Immunobiology Laboratory - More
In research on experimental type 1 diabetes using transplantation
techniques, Dr Charmaine Simeonovic’s group has found that targeting
chemokine receptors, rather than individual chemokines, may be useful
for pancreatic islet tissue transplantation.
- Professor Chris Parish
Cancer and Vascular Biology Group - More
Work in Professor Chris Parish’s laboratory provides the experimental
basis for a new approach to cancer vaccination that is potentially less
susceptible to immune evasion. These studies also imply that eosinophils
may play a previously unrecognised role in tumour immunosurveillance.
- Dr Marco Casarotto
Biomolecular Structure Laboratory - More
Studies on calcium receptors in muscle have allowed Dr Marco
Casarotto and colleagues to design small protein-like molecules (peptides)
that can regulate calcium levels in skeletal and heart muscle. Therapies
involving such designer molecules might ultimately be applicable to
a range of muscle-related diseases such as heart failure, malignant
hypothermia and muscular dystrophy.
- Dr Rohan Baker
Ubiquitin Laboratory -
Ubiquitin-specific proteases (USPs) are enzymes that split
the protein ubiquitin from deleterious proteins marked for destruction
in cells. The USPs can slow or prevent destruction of proteins or control
their locations in cells by this ubiquitin removal. One USP (USP4) can
cause cancer when in excess. Dr Rohan Baker has found that USP4 shuttles
in and out of the nucleus in normal cells but becomes trapped in the
nucleus of cancer cells. His group is now examining how this behaviour
is linked to cancer.
- Dr Greg Stuart and Dr John Clements
Neuronal Signalling and Brain Modelling Laboratory - More
The NMDA receptor is a protein in the brain that is thought
to be important for learning and memory. Work in the groups of Dr Greg
Stuart and Dr John Clements now shows that activation of these receptors
by voltage is time-dependent, fine-tuning this receptors' ability to
detect associative memories.
- Professor Trevor Lamb
Visual Neuroscience Laboratory - More
Professor Trevor Lamb’s analysis of a wide variety of
published results on dark adaptation and regeneration of visual pigment
in the human eye has produced some interesting findings at a molecular
level. The time course of the process appears to be set by the rate
of recombination of two molecules, 11-cis retinal and opsin. One outcome
of this research is that it is now possible to obtain an estimate of
the relative concentration of the critical molecule 11-cis retinal in
the living eye through single non-invasive measurements.
- Dr Scott Thomson
Vaccine Immunology Group -
Dr Scott Thomson has developed a scrambled antigen vaccine
approach, using consensus sequences of HIV, that might provide cross-strain
protection against infection.
-
Dr Greg Stuart
Neurological basis of memory - More
Investigation of the cellular mechanism underlying long term changes
in the strength of nerve connections in the brain has shown that repetitive
activation of nerves in the cortex of the brain enhances the activation
of certain receptors. This research increases our understanding of
how our brain makes memories with the potential to help in the development
of therapies to treat conditions associated with memory loss (eg Alzheimer's
disease).
-
Dr Pankaj Sah
A new GABA receptor in the amygdala -
The central nucleus of the amygdala (an almond-shaped organ in the
brain) contains receptors that are inhibited by benzodiazepines, for
example valium. We have found a new type of receptor which is a potential
target for new classes of drugs to manage anxiety.
- Professor Chris Parish
Cancer immunotherapy - More
We have found that secondary cancers in the lung can be cleared by tumour-specific
immune CD4+ Tcells in a process dependent on blood eosinophils. This
work, a collaborative study with Dr Paul Foster, provides the basis
for a new approach to cancer vaccination.
-
Dr Keats Nelms
Mining the genome for disease genes -
A process we have developed, called genome-wide chemical mutagenesis,
subtly alters the DNA code of hundreds of genes simultaneously in
a laboratory mouse using the chemical ethyl-nitroso-urea (ENU). The
ENU has its effect on genes by inducing random point changes or mutations
in the chemical sequence of DNA across the genome. Using this approach
we have identified over 50 new strains of mice that exhibit phenotypes
directly related to human disease. These include late and early obesity,
diabetes, neurological disorders and cancer. The information derived
from this genetic excavation will be critical in the development of
new therapeutic strategies for the treatment of a number of human
diseases.
-
Professor Chris Goodnow and Mr Stephen Martin
Molecular basis of immunological memory - More
Our ability to resist infection stems from a cardinal property of
the immune system, namely an ability to muster a much higher and faster
antibody response when the proteins that make up a virus or bacteria
are seen for the second time. We have defined a key role for a 'Tail
sequence ' of amino acids in the tail of the antibody. Steve Martin
has shown that the memory-type antibody tail dramatically increases
the number of progeny cells that are formed. This finding has wide
implications for vaccination, allergy and autoimmunity, where cells
bearing the memory tail are formed.
- Dr
Arno Müllbacher, Dr Eva Lee and Dr
Mario Lobigs
Mechanism of encephalomyelitis
The mechanism by which encephalic flaviviruses enter the brain to inflict
a life-threatening encephalomyelitis is obscure. We have shown that
the cell-destroying cytotoxic functions play a crucial role. Mice deficient
in pathways of cytotoxicity showed delayed and reduced mortality and
were resistant to a low dose peripheral infection with the virus.
-
Professor Peter Gage
New antiviral drugs -
The antiviral drug Amantadine blocks the ion channel formed by a protein
of the influenza A virus and depresses replication of the virus. We
have discovered a group of drugs that block the ion channels formed
by a protein from HIV and also depress HIV-1 replication in some cultured
cells. Our hypothesis is that blocking ion channels formed by some
other viruses may depress their replication also. Ion channels formed
by virus proteins represent a novel potential target for antiviral
drugs.
-
Dr David Tremethick
Turning genes on and off -
More
Gene regulation is connected to the three dimensional structure of
the genome. The basis for this structural organization is chromatin,
a specific complex of proteins and DNA. It has been established that
chromatin plays a fundamental role in maintaining regulated gene expression
but the process is not well understood. We have recently discovered
that major chromatin remodelling events occur during early mammalian
development with the essential histone protein variant, H2A.Z, being
specifically targeted to and compacting regions of the genome that
are not activated.
-
Professor Philip Board
GSTs - More
We have made a knockout mouse that is deficient in a protein called
glutathione transferase Zeta. The deficiency is not lethal but the
mice suffer from liver disease when they are exposed to high levels
of dietary phenylalanine. Studies of the GST proteins may be of importance
in understanding the mechanisms by which their over production contributes
to drug resistance.
-
Dr Simon Hogan
GM plants may be good for you
One major health concern of genetically modified plants in the human
food chain is their potential enhanced allergenicity and their ability
to predispose to allergic disease. We have been developing models
to assess the potential impact of consumption of genetically modified
plants in health and disease, in particularly allergic diseases. We
have demonstrated possible benefits to the immune system in consuming
genetically modified plants.
2001
- Histone H2A.Z - David
Tremethick
Histones are proteins that hold DNA in a compact structure called
chromatin. One of the histones, H2A.Z, is highly conserved species
from yeast to man. Our recent studies suggest that a major role of
H2A.Z is to regulate chromatin fibres to promote chromosomal regions
with specific functions in early embryonic development.
- Diabetes susceptibility gene - Robyn
Slattery
Experiments with mice that have an inbred susceptibility to diabetes
have led to the identification of the first gene known to confer susceptibility
to diabetes.
- Targeting genes - Klaus
Matthaei
Collaborative studies with Hugh Campbell (RSBS) have shown that the
gene known as flightless in fruitflies has a function as a key regulator
of the cytoskeleton in early embryonic development in the mouse, remarkably
analogous to its role in the fruitfly.
- Structure of an important receptor protein - Ian
Young
Three different cytokines involved in the regulation of blood cell
formation and inflammation have a common receptor. Collaborative studies
(with Ollis and Carr at RSC) have allowed us to define the three dimensional
structure of the extracellular part of the signalling entity of the
receptor. It has a novel double (or dimeric) structure which is clearly
important to its function of binding cytokines.
- Cancer vaccination - Chris
Parish and Paul Foster
The discovery of a mechanism by which the immune system attacks lung
metastases by a process involving eosinophils and the chemokine, eotaxin,
has provided a basis for a new approach to cancer vaccination that
is effective against cytotoxic T lymphocyte-resistant tumours.
- Viral hepatitis - Eva Lee, Arno
Müllbacher, Mario
Lobigs
Experiments with gene-targeted or natural mutant mice have shown that
the body uses different pathways in the immune system for fighting
viral infections. Our findings suggest that we may be able to devise
therapeutic means to either enhance recovery from viral infections
or to prevent or minimise immunopathological consequences of the hosts
immune response.
- Scrambled antigen vaccines - Scott Thomson
A new technology patented in 2001 will allow the development of more
effective and safe vaccines using a totally synthetic approach to
molecularly re-engineer whole pathogens or large numbers of antigens
simultaneously. It can also be used to combine multiple cancer antigens
safely into a single vaccine.
- Unexpected effect of nitric oxide - Bill
Cowden and Brett Charlton
In contrast to many reports in the scientific and medical literature
we have discovered that nitric oxide(NO) may actually slow down or
reverse the disease process. This finding may be important in devising
treatments for autoimmune disease.
- Brain receptor - Pankaj Sah
A novel type of receptor has been found in a region of the brain involved
in fear and emotions, called the amygdala. This may provide a key
target for the development of therapeutic drugs.
- Congenital deafness - Bruce
Walmsley and Sharon Oleskevich
Research on congenital deafness has revealed that disused nerve cell
connections in the brain are more powerful in early development. This
work provides insights into how the brain processes information generated
by electrical stimulation of the auditory nerve (cochlear implant)
in the congenitally deaf.
- Nerve cells in learning and memory -Greg Stuart
The role of the electrical properties of nerve cells in processing
signals from other nerve cells has been investigated. The results
have implications for the processes of learning and memory which may
lead to better treatments for brain disorders (for example Alzheimer’s
disease)
2000
-
A method of attaching special molecules to cell surfaces
has been developed. These target molecules will allow anti-cancer
drugs to be delivered specifically to cancer cells to stop them developing
their own blood supply. (C
Parish, J Altin)
-
Structural studies have revealed that the major signalling
entity of the receptor for three cytokines has a novel structure.
This may provide a basis for developing drugs useful in treating asthma,
allergy and cancer. (IG
Young, P Carr, D Ollis)
-
A precise sequence of amino acids, the "BCR Tail
Sequence", has been identified which seems to have a key role in the
phenomenon of immunological memory. This finding has wide implications
for vaccination, allergy and autoimmunity. (C
Goodnow, S Martin)
-
Studies on mutant forms of the E protein from Murray
Valley Encephalitis have shown that a loop (the FG loop) in the structure
has a functional role in the entry of the virus into cells. (E
Lee, M
Lobigs, A
Müllbacher)
-
Computer searches in a database which includes more
than a million DNA sequences has identified several new glutathionine
s transferases. Thes enzymes have been shown to have several activities
not previously known, including cell detoxification reactions. (P
Board)
-
Differences in the incidence and structure of gap
junctions in the blood vessels of normal animals and those which develop
high blood pressure as a result of a genetic defect have been identified.
The results suggest that there are important structural changes in
blood vessels which correlate with significant changes in blood vessel
function and blood pressure. (C
Hill)
-
Neurophysiological studies of normal and congenitally
deaf mice have shown that the inability of the latter to hear during
development results in a dramatic alteration in neurotransmitter release
between nerve cells in the appropriate part of the auditory system.
(S Oleskevitch, B
Walmsley)
1999
- Delineation, by D
Tremethick, of the role of H2AZ, a component of chromatin, which
may provide clues as to why so many human embryos die;
- The discovery by G
Ewart, Cox and P
Gage of a drug that stops AIDS virus replication;
- Identification by R
Baker of components of the ubiquitin pathway which controls
drug resistance and sensitivity;
- Demonstration by A
Ramsay of the role of nitric oxide in allergic disease, including
asthma;
- Discovery by P
Sah of a new type of GABA receptor in the amygdala, the part
of the brain involved in fear and anxiety, a possible target for new
treatments;
- New insights into morphine dependency using genetically altered mice
by I
Hendry and K
Matthaei;
- Discovery of gene pathways regulating autoimmunity and proliferation
of B lymphocytes, using gene chip technology by C
Goodnow and colleagues.
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