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Current Initiatives

Archive of Past Initiatives

ALZHEIMER'S DISEASE REASEARCH

 

a) Sir Zelman Cowen Universities Fund Alzheimer's Disease (AD) Research Grant

i) About the Grant and Awarded Project

As part of the Fund's 30th Anniversary celebrations, in April 2008, the Fund established the Sir Zelman Cowen Universities Fund Alzheimer's Disease (AD) Research Grant and called for applications from scientists of both the University of Sydney and the Hebrew University of Jerusalem. Joint applications for cooperative projects were also encouraged. The establishment of this project follows interest in the field of AD research developed by the Fund through its Alzheimer's Disease and Inflammation Initiative]] established in 1996.

Valued at $100,000, the AD Grant was for a research project in the field of Alzheimer’s disease, aimed at developing and/or assessing new treatments for this condition.

In September 2008, the Trustees announced the Award of the grant to University of Sydney scientists Dr Claire Goldsbury, Brain & Mind Research Institute and Dr Karen Cullen
, Discipline of Anatomy & Histology for their project: Energy deficiency as a cause of neuritic pathology in Alzheimer's Disease.

Scientists
Dr Claire Goldsbury & Dr Karen Cullen

The project focused on the process that causes the accumulation of tau, one of the two diagnostic abnormalities exhibited by the damaged nerve cells which characterise AD-affected brains. The researchers believe that understanding this process is important for identifying and developing new ways to treat AD. They say that, "Decline in energy metabolism, visible in AD brain scans, occurs in the same areas as the damaged nerve cells. The hypothesis on which the project was based is that reduced energy metabolism in the brain initiates the accumulation of tau. Using a multi-pronged approach, they set out to determine ways to short-circuit the pathway between energy depletion and brain damage by revealing the sequence of events that explains the abnormal accumulation of tau. They stated that they believed that understanding this process is important for identifying and developing new ways to treat AD.

ii) Final Report for AD Grant

Dr Claire Goldsbury, Brain & Mind Research Institute, USYD and Dr Karen Cullen, Discipline of Anatomy & Histology, USYD

Project: Energy deficiency as a cause of neuritic pathology in Alzheimer’s Disease.

Work commenced on the joint project in 2009 and was briefly interrupted by a period of maternity leave for Dr Goldsbury. The final report was submitted in late 2012 .

The project set out to achieve a better understanding of the process that causes the accumulation of a protein called tau in the brains of AD sufferers. An accumulation of tau is one of the diagnostic abnormalities of the damaged nerve cells in AD. It may contribute to nerve cell dysfunction by blocking trafficking of important components to synapses. Loss of synapses underlies the memory loss central to the disease.

Reporting on the project, Dr Goldsbury wrote, “In this project supported by the SZCUF, we have demonstrated that reduced energy metabolism by inhibition of mitochondrial function in cultured neurons gives rise to the redistribution of tau and cofilin into rod-like structures that appear to mimic those in the AD brain. Further, we demonstrated that the density of cofilin rods in human AD brains is significantly higher than in normal aged human brain. However, we also showed that some aged normal brains contained low levels of cofilin rods, although these brains were devoid of abnormal tau. This suggests that cofilin rod generation may be an early event in the neurodegenerative cascade representing a possible early-stage mechanism in the progression to AD dementia and therefore an ideal future target for therapeutic intervention that might be useful in treatment of neurological diseases.

Unexpectedly, however, despite an extensive study, we were not able to show any substantial microscopic overlap of tau and cofilin in the human AD brain. We conclude that the abnormalities involving cofilin and tau probably occur in parallel in different types of brain cells. This is a significant finding as it will direct future work that highlights the important role of non-neuronal cells in the mechanism of neuronal cell death in the AD brain.

The work we performed with the SZCUF grant resulted in 4 publications in highly ranked international journals (3 published, and 1 soon to be submitted) demonstrating a significant contribution to the AD research field.”

b)Alzheimer's Disease Research Projects

i)How Senile Plaques Form In The Aging And Demented Brain: The Roles Of Haemorrhage And Macrophages

Prof Jonathan Stone, Dept of Physiology, USYD; Prof Eli Keshet, Faculty of Medicine, HU

This project follows on from The Microvascular Basis of Alzheimer's Disease, a collaborative project involving Prof’s Stone and Keshet together with Dr Karen Cullen & Prof Nick Hunt of the University of Sydney. That project established the concept that senile plaques form at the site of cerebral microhaemorrhages.

The current project aims to show that macrophages - specific cells that appear at the site of tissue damage such as stroke, to clean-up debris of dying cells - actively form plaques. If confirmed, this outcome will accelerate acceptance of the critical issue, that age-related dementia is a vascular disease, for which prevention, treatment and relief of symptoms will be found in the stabilization of blood vessels, the reduction of vascular risk factors and the treatment of the thousands of mini-strokes which threaten the aging brain.

Prof J. Stone
Prof E. Keshet

Giving his first report to the Trustees in December 2010, Prof Stone reported good progress on the project with 5 papers having been presented at major conferences/meetings providing evidence from the group’s research to support their hypothesis. The final report from the project is due in early 2013.

ii) The Microvascular basis of Alzheimer’s Disease - Report from Prof Eli Keshet (Hebrew U)

In his final report on this project in December 2010, Prof Keshet rounded-off work commenced originally in collaboration with Dr Karen Cullen & Profs Stone & Hunt, University of Sydney.



The original aim of the project was to use genetically engineered mice produced in Prof Keshet’s lab to gain further insights into the mechanisms at a cellular level by which AD is caused. The working hypothesis was that the triggering event in AD development is a cerebral vascular injury causing extra-cellular deposits (EDC’s) at the site of the vascular injury. This was confirmed in early work using the transgenic mice. 

More recent work with these mice has also provided insights into the role of a vessel growth factor (VEGF) in brain cell formation and improvement of learning and memory.


In using the transgenic mouse produced by his lab to produce these results, Prof Keshet has concluded that the model has been shown to be appropriate to critically examine the working hypothesis of a vasculo-centric origin of AD development. In addition the model has successfully shown a variety of ways in which the hippocampal vasculature may affect cognitive function.

THE BOSCH INSTITUTE, UNIVERSITY OF SYDNEY

 

Following the success of grants previously awarded to infrastructure projects in the Bosch Institute (U Sydney), the Fund has undertaken to support two further Bosch Institute infrastructure projects. Previous grants supported salary for an officer to manage a Molecular Biology Facility (2001-2005) and a Flow Cytometry Facility (2006-2008). Both facilities have given Institute members access to state of the art equipment essential in current biological research and they have formed the model for further joint facilities within the Institute. By demonstrating the value of such facilities, they have assisted in raising funds from major granting bodies to expand and maintain all these facilities. The new grants will again support salaries for Officers to manage the two new facilities.

a) Animal Behaviour Facility (ABF)
Rodent behaviour is a rapidly growing area of research worldwide which will underpin current and future Bosch research in neuroscience, infectious disease and gene function analysis. The activities of this Facility will be integrated with those of the existing Facilities, providing a comprehensive suite of approaches to complex biomedical research projects. The establishment of the ABF and the availability of the ABF Officer will provide an enormous boost to many research programs within Bosch, resulting in greater scientific and medical achievements and increasing its scientists’ opportunities to win grant support for research projects and research infrastructure.

ABF Officer Thomas Burton

b) Oxidative Stress Bioanalytical Facility (OSBF)
In many non-communicable diseases, including cardiovascular diseases, cancer, neurodegenerative disorders, ageing, diabetes and obesity, as well as in many infections, increased oxidative stress is linked to tissue damage. To understand the role of oxidative stress and to test potential mechanisms for controlling its associated damage in disease requires knowledge of the precise location, identity and levels of oxidants involved. The OBSF will provide unique and advanced technology to localize, characterize and quantify biologically relevant oxidants in cells, tissues and organs and allow scientists to define how changes in cellular oxidative stress affect biological processes relevant to health and the pathogenesis of many diseases. In addition, OSBF facilities will contribute to future drug discovery and the monitoring of drug efficacy and responses to treatment of diseases.

OSBF Officer Magda Lam in the OSBF


PROMOTING COLLABORATIVE WORK - UNIVERSITY OF SYDNEY/HEBREW UNIVERSITY

 

a) SZCUF Bosch Institute (USYD) and Institute For Medical Research (HU) Academic Exchanges Project Grant

This project was initiated by the Bosch Institute with financial support from the Fund to develop a long-term collaborative relationship between the two Institutes through staff & research student exchanges which could lead to research collaborations and possibly attract international funding. The following collaborations have resulted:

  • Prof Des Richardson (USyd) & Prof Shulamit Katzav (HU) – iron chelators and cancer
  • Prof Des Richardson (USyd) & Prof Ron Dzikowski (HU) – anti-malaria compounds which inhibit the growth of the malaria parasite even at very low dosages
Prof Shulamit Katzav and Dr Ron Dzikowski from HU visited Sydney in 2008 to start the program.

b) UNIVERSITY OF SYDNEY – ISRAEL RESEARCH PARTNERSHIPS FORUM: Shared Challenges, Future Solutions
The Forum, which took place in November 2011, was an initiative of the University of Sydney. The foundations for the Forum were laid by the Fund’s SZCUF Bosch Institute (USYD) And Institute For Medical Research (HU) Academic Exchanges Project Grant. The forum aimed to enable scientists of the University to share ideas with scientists from various Israeli academic institutions including the Hebrew University of Jerusalem, the Technion and the Weizmann Institute and to foster collaborative research between University of Sydney researchers and colleagues in Israel.

In addition, the Program for the week provided opportunities for interactions between researchers and appropriate government and non-government authorities and/or commercial interests. The highlight of the program was a Symposium on 31 October 2011, at the University of Sydney which included a plenary session featuring a number of distinguished speakers and workshops focused on the themes of the Forum which were:

  • Medicine: Neuroscience, Cancer/stem cells, Obesity/diabetes
  • Water, Food and Agriculture
  • Pedagogy of teaching second language
  • Energy, IT, Business

The Fund was a major sponsor of the Forum having undertaken to support travel and accommodation expenses for the 3 Hebrew University academics invited to participate in the Forum.

Israeli presenters at the Forum (L to R) with NSW Chief Scientist, Prof Mary O’Kane, who opened the Symposium: Profs Manuel Tov, Dror Seliktar, Moshe Phillips, Baruch Schwarz, Mary O’Kane, Yael Ziv, Michal Schwartz, Gideon Grader, Meni Ben-Hur