The University of Queensland (Brisbane, Australia) recently announced that an impressive $10 million of its latest capital campaign would be directed to its Queensland Brain Institute (QBI) to support the work of Dr. Jürgen Götz and his team of researchers at the Clem Jones Centre for Ageing and Dementia Research (CJCADR). As QBI completes the necessary steps toward initiating their first focused ultrasound-based phase 1 clinical safety trial for patients with Alzheimer’s disease, we interviewed Dr. Götz to learn more about CJCADR and the progress that he and his team have been making over the past several years.
Since our 2015 investigator profile, Dr. Götz has grown his group to 25 scientists, technicians, and engineers who are not only seeking to treat Alzheimer’s and other neurodegenerative disorders, but who are also working on multiple facets of these devastating diseases, with a major focus on understanding basic pathomechanisms.
What is the research site name and location?
The Queensland Brain Institute is located at the University of Queensland in Brisbane, Australia. It houses four Institute Centers:
- The Clem Jones Centre for Ageing Dementia Research (CJCADR) is focused on research into the prevention and treatment of dementia.
- The Asia-Pacific Centre for Neuromodulation (APCN) seeks to use deep brain stimulation to revolutionize the diagnosis and treatment of neurological diseases.
- The Science of Learning Research Centre (SLRC) identifies research and seeks to understand effective teaching and learning practices in the light of current knowledge about basic learning processes and factors that influence successful human learning.
- The Joint Sino-Australian Laboratory of Brainnetome is a joint initiative with the Chinese Academy of Sciences' Institute of Automation (CASIA), in Beijing.
When was QBI started, who started it, and why?
The University of Queensland is comprised of a series of Institutes and faculties. Approximately 15 years ago, in 2003, the State of Queensland launched a “Smart State” initiative where the Premier pushed to transition the economy from natural resources to more sustainable programs, such as biomedical research. A philanthropist, Chuck Feeney, gave several million dollars to establish QBI as a new institute, which has now grown to support 44 faculty and 450 technicians, engineers, and support staff. QBI currently has 39 various research groups.
A former mayor of Brisbane, Clem Jones, left a substantial amount of money after he passed away to create a foundation dedicated to medical research. In 2012, with $9M from the state and $9M federal funding, the Clem Jones Foundation helped to create CJCADR to expand the work into dementia research.
What is the name of the focused ultrasound research laboratory?
The Götz Laboratory is a part of CJCADR. [Note: Professor Götz is also the Director of CJCADR.]
Describe your facilities, space, and equipment.
QBI has nine specialized core facilities that provide its researchers with cutting-edge technologies together with research support.
What is the vision or mission of QBI?
QBI’s vision is to unlock the mysteries of the brain to understand and treat diseases, improve learning and memory, and inspire technology. By discovering the fundamental mechanisms of brain function, disorders of the brain can be prevented and treated. QBI believes that understanding the development, organization, and function of the brain, including the function and dysfunction of its neural circuits, leads to the development of better behavioral outcomes and novel therapies for disorders such as dementia, Parkinson’s disease, schizophrenia, motor neuron disease (MND), anxiety, and depression. QBI also aims to use the understanding of brain function to improve learning in classrooms and in the workplace.
Where does your funding come from, and what is your annual budget?
The funding of the Götz Laboratory comes from two Federal grant organizations, the ARC (Australian Research Council), and the NHMRC (National Health & Medical Research Council). Additional significant funding is from the State and Federal government, as well as many philanthropic organizations (Clem Jones Foundation, McCusker Foundation, Brazil Foundation, the John T Reid Foundation and others).
Which focused ultrasound applications and biomechanisms are being investigated?
For focused ultrasound, we are primarily using it to open the blood-brain barrier (BBB).
How many different studies are being conducted at this site, and what are your projects?
CJCADR takes a comprehensive approach to studying dementia. From pathology and biochemistry to the use of gene edited mouse models and the use of 2-photon microscopy to learn how focused ultrasound actually opens the BBB, this comprehensive team of scientists is tackling dementia from every possible angle. Researchers at CJCADR are studying each of the following aspects of dementia:
The Pathology of Alzheimer’s Disease and Dementia.Understanding the way that these diseases truly begin to attack the brain can lead to new ideas for prevention. Toward this goal, CJCADR published a paradigm-shifting study in late 2017 proposing an alternative mechanism for how tau accumulates in brain cells in Alzheimer’s disease (see EMBO J). The study found that tau does not relocate from another part of the cell; instead, it is newly synthesized in the areas where it accumulates. That same year, another CJCADR high-impact study described how tau accumulation reduces synaptic activity and hippocampal neuronal excitability by moving the axon initial segment. The hippocampal excitability is an aspect that had never before been described. Furthermore, this study also showed that pharmacological stabilization could prevent the deficits caused by pathological tau accumulation (see Acta Neuropathologica). The group has a long-standing interest in how tau and amyloid impair mitochondrial functions and has just published another paper (see EMBO J)showing that and how tau impairs the removal of damaged mitochondria.
The Biochemistry of Opening the BBB. Researchers at CJCADR are studying the biology of using focused ultrasound to open the BBB. QBR’s Advanced Microscopy facilityprovides state-of-the-art instrumentation, experienced staff, and researcher support for rapid imaging of neural activity down to the cellular level (e.g., synaptic function).
Mouse Model Development and Tools for Gene Editing.CJCADR scientists are also interested in using genetics to understand – and then potentially interfere – with the development of neurodegenerative diseases. QBI’s DNA sequencing facility has a platform that can perform whole genome sequencing (WGS), targeted resequencing of individual exomes and regions of interest, gene expression and regulation, small RNA discovery, methylation profiling, and genome-wide protein-DNA interaction analysis. More than 20 years ago, Dr. Götz’s first publication describing a tau transgenic mouse model set the stage for targeting tau in humans (see EMBO J). In 2010, the CJCADR group discovered that the two hallmarks of Alzheimer’s disease, amyloid-β and tau, were linked in the dendrite part of the neuron (see Cell); they then achieved isolation of the Alzheimer’s disease-associated phenotype in mice, both genetically and pharmacologically, a paper that has been cited more than 1,000 times. As an international expert on these models, Götz has authored seven reviews in the Nature Reviews series, including his latest article on transgenic Alzheimer's mice models (see Nature Reviews Neuroscience).
Technical Ultrasound Studies.CJCADR has developed new techniques for using focused ultrasound as a delivery tool and novel treatment modality. One of the team’s landmark publications in 2015 was the first to demonstrate amyloid clearance and improved memory function in a mouse model of Alzheimer’s after BBB opening with scanning focused ultrasound (see Science Translational Medicine). More recently, CJCADR researchers published a first-of-its-kind study that showed that scanning ultrasound could both reduce the formation of tau tangles and enhance the uptake of a therapeutic antibody fragment (RN2N) in a mouse model (see Brain). Dr. Götz has written several reviews and commentaries on ultrasound treatments for neurological disorders.
Who are your key Investigators?
QBI currently has 39 different research groups. Their research interests, professional history, and credentials can be found on the QBI website.
Who are your internal and external collaborators?
QBI has an impressive list of partnerships that range across academia, industry, and government.
What is next for CJCADR?
Completing all of the steps to initiate our first Alzheimer's disease clinical safety trial. This will become the successful translation of years of laboratory work.
What is the role of the Focused Ultrasound Foundation in your work?
The Foundation is an excellent advocate for therapeutic ultrasound and an able facilitator of bringing different stakeholders together. Without its vision and engagement, the field would not be where it currently stands.
What is your wish list to increase your impact (funding, people, technology)?
For anyone working in the therapeutic ultrasound space, the wish is that this technology will be embraced by the regulatory bodies, the reimbursement schemes, and the clinicians who will ultimately apply the technology. QBI’s vision is that ultrasound continues to develop into a tool to better understand brain function. I appreciate the friendly and supportive attitude in the therapeutic ultrasound community. More funding is needed to achieve a faster implementation for ultrasound to treat diseases of the brain.
Photos courtesy of Queensland Brain Institute. Credit: WilsonArchitects.com.au