Integrated Drug Design for a new generation of adrenergic
therapeutics.
Project Summary:
Fundamental to our ability to respond to both immediate and long-term
environmental changes and stresses is the coordinated regulation of cellular
functions by hormonal and neurotransmitter stimuli. The great majority of such
stimuli are "sensed" by complex glycoprotein receptors on the surface of most
cells that selectively bind and are activated by various hormones and neutrotransmitters.
Although there are several hundred distinct, but structurally related receptors
of this kind, including the adrenergic receptors (ARs), molecular mechanisms
involved in their activation and, thus, the regulation of vital cellular the
functions remain unclear. Based on insights that we have gained from the development
and characterisation of several mutated ARs, we have developed a model of receptor
activation. In this application we propose to further test and extend the hypotheses
underlying this model. Importantly, the functions regulated by ARs include vital
responses, such as the maintenance of blood pressure by augmenting heart pump
function and by constricting vascular smooth muscle. In addition, disordered
cellular regulation by ARs has been implicated in a wide variety of diseases,
including high blood pressure, congestive heart failure and enlargement of the
heart. Thus, the studies detailed here to further understand the molecular mechanisms
of receptor activation have broad implications for our knowledge of critical
physiological control systems, and may lead to novel therapeutic approaches
to treat a variety of diseases, including also tumours of the adrenal gland
that cause excess adrenalin secretion.
Chief Investigator(s):
Anatoly Rozenfeld
2001 $
2002 $
2003 $
Total $
$125,000
$125,000
$110,000
$360,000
Funding Type:
Development
Project Title:
Development of a PET detection system prototype with
depth of interation capability
Project Summary:
This development project involves the development of a slim-line
Positron Emission Tomography (PET) detection sub-module, the crucial component
of PET scanners, that is small and extremely flexible. It is planned to utilise
this module in the design of customised new commercial PET scanners ideal for
diagnosing human brain and breast disorders. The development will proceed in
collaboration with Insight Oceania/ADAC, Sydney. PET is a functional imaging
tool, which is able to quantify physiological and biochemical processes in vivo,
using short-lived cyclotron-produced radiotracers. PET is emerging as an extremely
important diagnostic procedure used in the early detection of cancers, neurologica
diseases and as an aid in treatment monitoring and drug development. The unique
advantage of PET however, is not being completely utilised due to constraints
of the current design of PET scanners.
Chief Investigator(s):
Roger Truscott
Joanne Jamie
2001 $
2002 $
2003 $
Total $
$75,000
$75,000
$75,000
$225,000
Funding Type:
Project
Project Title:
Understanding the role of human lens UV filters in age-related
cataract.
Project Summary:
Cataract is the most common cause of blindness worldwide. The
cause of cataract is currently unknown and the only treatment available at present
is surgery. This represents a huge burden on the Health budgets of all developed
nations, including Australia. It has been estimated that if a treatment could
be developed that simply delayed the onset of cataract by 10 years, the need
for surgery would be halved. The savings to the Health budget in the USA alone
would be approximately $2 billion (US). We believe, on the basis of our previous
research, that human lens UV filter compounds play a major role in the protein
modification that is the hallmark of age-related cataract and indeed may be
the key factor in precipitating cataract. This proposal seeks to confirm this
hypothesis. If this theory is confirmed, it opens the door to pharmacological
intervention for a cataract by, for example, treating patients (or possibly
all people in middle age) with drugs that inhibit the synthesis of the UV filter
compounds.
