Translating >> - Westmead Millennium Institute

12 13 > Overview // AR 2006
The positive benefits lasted only a few years, and the
centre is now leading a larger Australian consortium, with
substantially increased Federal Government funding, which
is being administered by the Juvenile Diabetes Research
Foundation. The aim is to examine anti-rejection treatments
that may reduce the risk of islet cell grafts failing. The
researchers hope to develop safer and more effective processes
for islet transplantation and to have a better understanding of
what happens to the graft after it has been transplanted.
Dovetailing this field of research is the centre’s pioneering
work aimed at creating a limitless supply of insulin producing
cells using modified pigs as the source. In collaboration with
a numbers other researcher groups the centre is investigating
ways to design pancreatic islet cells that can be taken from
pigs that will be more resistant to the human immune system.
The Centre for Virus Research is a world leader in research
on human immunodeficiency virus (HIV) and the herpes
group of viruses including herpes simplex virus (HSV),
cytomegalovirus (CMV), and Varicella Zoster virus. The
Centre’s main focus is to identify how these viruses infect
patients to develop ways to diagnose, treat or prevent them and
their transmission in the international and local community.
In 2006 an estimated 40 million people were infected with
HIV worldwide. The centre has helped identify how HIV
infects patients via host cells called dendritic cells, which are
found in the lining of the genital tract. In women, this lining
is thinner and less protected than in men. Understanding
how these early interactions occur is encouraging the
development of ‘microbicides’ or decoys, which may stop
the virus from entering cells of the genital tract. The Centre
is now collaborating with a biotechnology firm to develop
novel candidate microbcides.
Centre researchers are also using sophisticated techniques
to study how HIV induces changes in hundreds of human
genes that simultaneously occur within a single infected
dendritic cell. Other important work is directed at how a
group of people infected with a weaker strain of HIV have
been able to naturally control it. Recently, this work has
led to the discovery of defensive proteins, which appear to
control HIV in these patients.
Cytomegalovirus affects about 60 per cent of the population.
It is usually controlled in healthy people, but can be fatal
in immunosuppressed people such as those who have
undergone bone marrow or solid organ transplants.
Researchers have been defining the mechanisms that keep
CMV dormant and the chemical interactions that trigger its
activation. This work has led to the discovery and patent of a
type of interleukin-10, a protein that inhibits key functions
of immune cells.
Shingles is a painful condition affecting many elderly
individuals caused by re-emergence of dormant Varicella
virus years after causing chicken-pox. An exciting research
project is underway that may provide insight into the
molecular immune processes which allow this and then
control the re-emergence. With ethics permission, autopsy
material from patients who have passed away at the time of
a shingles episode are being used to identify such immune
mechanisms in the hope of improving the success rate of
current vaccine (about 60 per cent).
The centre has already pioneered work showing how herpes
simplex virus travels in nerves between the site of infection
on the skin and the site of dormant infection near the spinal
cord. When the virus is activated, it travels back to the skin
surface to present as cold sores or genital herpes. The Centre
is unraveling mechanisms that trigger this viral activity to
produce blocks that may stop the outbreaks. Negotiations
with a US biotechnology firm are underway to fund this
research in return for licensing one of the centre’s patents.
Research into HSV type 2 is significant because it causes
genital herpes and enhances HIV by up to three times. The
vaccine Simplirix, which was developed some years ago
based on discoveries made by the centre, is being retrialled
in the US with availability forecast within about three years.
Simplirix has shown to be about 75 per cent effective against
genital herpes infection in women who have never previously
had HSV. Centre researchers are examining how immune
processes control virus infection in an attempt to improve the
vaccine to protect previously infected women and also men.
In particular, work on how immunity to HSV type 1 (which
usually causes cold sores) can control HSV type 2 is about to
be patented.
The Institute of Dental Research investigates the causes
of major oral diseases to design new and better treatment
options for patients. As both tooth decay and chronic gum
infection (periodontal disease) are major health burdens for
Australian communities, the Institute’s work is critical.
Ongoing research into the microbiology of progressive tooth
decay has identified a particular group of bacteria that attack
the tooth nerve in the final stages of decay. Researchers are
currently investigating new diagnostic methods that can be
used in the dental surgery to predict the invasion by these
bacteria, so that more conservative approaches to treatment
may be applied. For the patient this may mean retaining
the living tooth rather than undergoing more complex and
invasive therapies, which often leave the tooth susceptible to
fracture leading to even more complicated treatments at a
later stage.
The Institute is also developing a new anti-bacterial
compound that may be able to target specific diseases or
bacteria in the mouth and gums so that protective bacterial
flora (good bacteria) are not destroyed during treatment.
Current therapies still rely on broad-spectrum antiseptics or
antibiotics, which wipe out good and bad bacteria present
in the mouth. While tests are at an early stage, the eventual
outcome may see low-cost treatments such as toothpastes or
mouthwashes containing the specific anti-bacterial available
in supermarkets.
The Institute for Immunology and Allergy Research
investigates diseases caused by abnormal functioning of the
immune system. This includes many major unsolved diseases
that plague communities worldwide. The Institute’s research
programs focus on three main themes: autoimmune disease
such as multiple sclerosis (MS); allergy disorders such as
eczema and asthma, and why individuals vary so much in
their response to infection with HIV and hepatitis C viruses.
Collaborative research on the genetics of severe eczema and
asthma in children has led to the discovery of a link between
these diseases and several genes that are important for normal
immune function called TIM-1, TIM-3 and PHF11.
Researchers know TIM-1 and TIM-3 are expressed on the
surface of specific types of immune cells and relay messages
inside the cell, leading to cell activation through the turning
on or off of specific genes. The Institute has now made
important advances in understanding how PHF11 operates,
showing that it is present deep inside a cell and directly
controls the switching of genes on or off. Researchers are
now investigating whether these genes interact to influence
susceptibility to disease. Although still at an early stage,
this research may guide the development of new drugs and
topical therapies.
Major research is also being conducted on a gene crucial to
the immune system’s healthy functioning called Interleukin
7 receptor alpha chain or CD127. In 2003, the Institute was
the first to publish findings that a genetic variant of CD127 is
important in the development of MS. The researchers believe
this is due to its role in generating regulatory T cells, which
stop the immune system from attacking the body’s own
tissue and have submitted at patent application for improved
therapy based on this discovery. Three international research
groups have recently confirmed this discovery making
CD127 only the second clearly established genetic risk factor
in MS after HLA (a cell’s identification markers). As a result,
CD127 has become one of the hottest areas of research into
MS strengthened by the potential to design treatments to alter
the abnormalities found in the gene’s function.
In other research, the Institute was awarded an Australian
Research Council Linkage Project grant to collaborate with
the pharmaceutical company Biogen IDEC to investigate
why up to one-third of MS patients fail to benefit from
interferon, the disease’s main treatment therapy.
NHMRC grant funding is also supporting research between
the Institute and the Storr Liver Unit to investigate the
genetics of hepatitis C. About 35 per cent of individuals fully
recover from the hepatitis C infection due to their immune
system clearing the virus from their body. The remaining
65 per cent of patients fail to clear the virus and may go
on to form cirrhosis and liver cancer. Based on these data,
researchers are examining the factors in patients’ genetic
makeup that determine disease outcomes when infected by
the virus.