Neuroscience News Summer 2014 section

Body mass may be more nurture than nature

Body mass may be more nurture than nature

Researchers have found the influence of genes on body mass index (BMI) scores is substantially lower than previously thought.

Conducted in Professor Peter Visscher’s laboratory, the study provides new insight into the genetic causes underlying a person’s score on the body mass index.

Lead researcher, Dr Gibran Hemani, says there is debate as to the degree to which genetics contributes to BMI.

“Some studies claim that more than 80% of BMI is due to genetic factors with less than 20% being driven by environmental factors, whereas others have put the figure much lower.

“We wanted to come at the question from a different angle, using very large and complex sets of data and a method that is more reliable than previous studies,” Dr Hemani said.

Human DNA varies at millions of positions across the genome, and trying to figure out if, how, and how much, these genetic variations lead to differences in BMI is gradually becoming understood.

Dr Hemani and his colleagues from Australia and Europe obtained DNA data on 20,240 pairs of siblings.

On average, if an individual has a variant at a particular position in the genome then his or her sibling will have a 50% chance of sharing that same variant.

By counting the total number of DNA variants shared across the whole genome, the team could identify the genetic similarity (or dissimilarity) of siblings.

They found that although on average siblings were 50% genetically identical, the exact figure varied from about 35% to 65% meaning that some sibling pairs are more genetically similar than others.

Using this method, Dr Hemani and his colleagues calculated whether siblings who were more genetically similar were on average more similar in terms of BMI.

The group found that approximately 42% of BMI is under the influence of genetics.

Dr Hemani said the study also has contributed in other ways in trying to understand how genetics influence BMI.

“We know that there are a huge number of variants across the genome, but how many of them actually have a direct influence on a complex trait like BMI?

“This is an important question because many researchers who study disease are focussed on one particular genetic change or a gene of interest as the cause of the disease, however, there is growing evidence, including from this study, that disease is caused by thousands of small changes and it’s the additive effect of these changes that results in disorder.”

Centre opened to understand the science of learning

Centre opened to understand the science of learning

The 27th of November marked the official opening of a new research centre combining neuroscience, education, advanced imaging and psychology to enhance learning.

Opened by the Minister for Science, Information Technology, Innovation and the Arts, The Hon Ian Walker MP, the Science of Learning Research Centre (SLRC) is a Special Research Initiative of the Australian Research Council, which brings together researchers from different disciplines who, in collaboration with educators, want to understand what leads to successful learning.

The research conducted in the Centre will aid the design of effective and practical techniques that facilitate learning and permit better assessment to the benefit of all Australians.

“The objectives of the SLRC are to identify, research and understand effective learning practices in the light of current knowledge about basic learning processes and factors that influence successful human learning,” says Professor Perry Bartlett, whose vision inspired the Centre.

“The establishment of the Science of Learning Research Centre will, for the first time, allow us to take what we know about how the brain learns and translate that into educational outcomes,” he said.

“A bench top to blackboard approach is revolutionary for the learning community.”

The collaboration brings together researchers from three lead institutions: UQ, the University of Melbourne, and the Australian Council for Educational Research, as well as Flinders University, Deakin University, University of New England, Charles Darwin University, and Macquarie University.

Mr Walker says this novel approach has the power to influence the educational outcomes for generations to come.

“To meet the challenges of the future, Queenslanders young and old will require lateral thinking, forward thinking, and creativity,” he said.

“The SLRC will bring new perspectives to teaching and education – from pre-school through formal education to life-long learning.

“This kind of research is another way we can shape a better, brighter future for the people of Queensland.”

UQ’s Professor Ottmar Lipp, inaugural Director of the Centre, says the SLRC will place learning at the focus of its research and develop an evidence-based approach to educational practice.

“This collaboration will be facilitated by the centrepieces of the Centre, two experimental classrooms one at UQ and one at the University of Melbourne.

“It is essential that this is done in collaboration between researchers from different disciplines on the one side and practitioners on the other.”

Director's Message Summer 2014

Director's Message Summer 2014

In this edition of Neuroscience News we highlight the tremendous recent success of the Institute.

Consistent with previous years, we were extremely successful in the recent round of National Health and Medical Research Council (NHMRC) grants, with 17 projects being funded, a success rate of 44.7% – far higher than the 16.7% national average. These highly competitive grants are awarded following a rigorous process in assessing almost 4,000 applications nationally, involving 170 Assigners Academy members, more than 7,800 written peer reviews, and more than 600 grant review panel members.

QBI also achieved a 44.4% success rate in the Australian Research Council (ARC) Discovery Project grant round, which was again significantly higher than the 19.9% national average.

Congratulations also to Dr Jian Yang, who has been awarded more than $1 million to unlock the genetic underpinning of thousands of diseases including schizophrenia, obesity and cancer. As one of two recipients of the highly prestigious Sylvia and Charles Viertel Charitable Foundation’s Senior Medical Research

Fellowship, Dr Yang will receive $245,000 per annum for 5 years. This is a wonderful achievement and recipients of this prestigious Fellowship have historically become leaders in their field of science. In fact, QBI’s Deputy Director (Research), Professor Pankaj Sah, was the first recipient of this Fellowship when it was launched in 1995.

I am also pleased to announce that QBI has joined with the QIMR Berghofer Medical Research Institute and the Queensland Centre for Mental Health Research to form the Queensland Mental Health Research Alliance. This alliance was formed with the goal of advancing the understanding of mental disorders and improving outcomes for patients. Mental illness is a leading cause of health related disability in Queensland, as well as a global health challenge. Together we will work towards discovering the neurobiological links in mental health disorders, which can help develop prevention methods and effective treatments.

Lastly, I wish to thank the Government for their ongoing support of the Institute. Grants awarded by the NHMRC and ARC, along with our recent State and Federal funding towards the Clem Jones Centre for Ageing Dementia Research, provide us with the financial support to work towards understanding the overwhelming tide of neurological diseases, which accounts for a staggering 40% of the disease burden in Australia.

Professor Perry Bartlett FAA
Director, Queensland Brain Institute

Events and Congratulations

Events and Congratulations

Special Events

Surgeon’s quest for a cure

After years of losing patients to brain tumours despite having access to the best of modern medicine, a Brisbane neurosurgeon has had enough.

Dr Sarah Olson has teamed up with businesswoman and philanthropist Beverley Trivett of the John Trivett Foundation to raise funds for brain tumour research.

“I had a sudden epiphany one day when I realised that surgeons such as myself cannot cure brain tumours,” Dr Olson said.

“Only research holds the key to improving treatments for these devastating cancers, so by investing in our most promising researchers today, we can make a difference in the treatment available tomorrow.”

The John Trivett Foundation is raising $1.5 million for a senior research fellow to be based between two institutes at UQ: the Institute for Molecular Bioscience (IMB) and QBI.

Professor Perry Bartlett said the support of the John Trivett Foundation would coalesce the city’s brain cancer research.

“There are several different laboratories working on brain tumours at QBI, IMB and beyond, but no single group is solely focussed on these cancers,” Professor Bartlett said.

www.johntrivettfoundation.org.au

Recent Events

7th A+PD

QBI opened its doors to more than 175 delegates, including 25 esteemed speakers, from around Australia and across the globe for the 7th Alzheimer’s and Parkinson’s Disease Symposium (A+PD) in September.

Like previous symposia, the event brought together a distinguished range of international and Australian speakers presenting and sharing their latest discoveries in the field of neurodegeneration.

The impressive speaker line-up included a Keynote Lecture from the University of Melbourne’s Professor Ashley Bush, who was recently awarded a prestigious NHMRC Fellowship in recognition of his ground-breaking work in the diagnosis and treatment of Alzheimer’s disease.

Attendees heard from researchers from the United States, China and Germany, with international Keynote Lectures being given by Professors Christian Behl (University of Mainz), Christian Haass (German Center for Neurodegenerative Diseases, Munich) and Angus Nairn (Yale University).

Organised by Professor Jürgen Götz (QBI) and Professor Lars Ittner (University of New South Wales), the event alternates on an annual basis between QBI and the University of New South Wales.

Merson Lecture

New York University’s (NYU) Professor Gordon Fishell shared his insights into wiring and disease in the nervous system at the annual Merson Lecture.

“The nervous system, like all biological systems, self-assembles,” said Professor Fishell.

“They achieve this by mutual signalling between the neural cell types that comprise it.”

Inhibitory cells, he explained, act as the yin to the excitatory cells’ yang.

Excitatory cells carry information and allow an external world to be internalised and represented in the brain.

“The inhibitory cells, the cortical interneurons, keep the excitatory cells in check and prevent the networks from overloading and causing problems such as epilepsy or schizophrenia,” he said.

Professor Fishell’s laboratory explores the developmental events by which these cells acquire their identities.

“What we have discovered is that the very electrical signals that ultimately allow us to perceive the world are the same ones that are used to assemble our nervous system.”

Not all dysfunction results in brain disease according to Professor Fishell’s research. “A false dichotomy is that disease can be caused by genes or environment, while in fact the two are interlinked.

“Environment affects gene expression and genes affect environment.”

Welcome

Luke Sartor is the recipient of this year’s Aleks Brumby Scholarship.

With a Grade Point Average of 6.889 out of a possible 7, Luke was selected out of a final list of 16 candidates based on academic merit and research potential.

During the QBI Summer Research Program for 2013/2014 he will work closely with Professor Linda Richards and Dr Jens Bunt.

Federal Government supports QBI

Federal Government supports QBI

The Federal Minister for Health and Minister for Sport, The Hon Peter Dutton MP, made his first official visit, in his new portfolio, to QBI.

The visit followed Prime Minister Tony Abbott’s announcement of $9 million in funding for the Clem Jones Centre for Ageing Dementia Research (CJCADR) as part of the Coalition’s overall national commitment of $200 million to accelerate the research towards a cure for dementia.

In further support of the Institute, in November Mr Abbott announced QBI is to receive $11.865 million from a total of $559.1 million in funding awarded to Australian health and medical researchers to generate new health discoveries.

Funding from the National Health and Medical Research Council (NHMRC) includes the promotion of two faculty members – Professor Joe Lynch and Professor Fred Meunier – within the research fellowship scheme.

Professor Bartlett says the Federal Government’s support for fundamental neuroscience research into the mechanisms regulating brain function and disease resonates with the national health priorities.

“These grants, along with philanthropic and additional Federal and State Government support, provide us with a real opportunity to gain a deeper knowledge of the underlying mechanisms and develop new therapeutics to treat mental and neurological diseases,” Professor Bartlett said.

QBI also obtained a 45% success rate in the Australian Research Council (ARC) Discovery Project grant round.

Among the successful applicants was Professor Mandyam Srinivasan, who was awarded two grants, the maximum number able to be awarded under this scheme, totalling almost $1.5 million.

One of these grants also included a prestigious Discovery Outstanding Researcher Award. Professor Srinivasan will use high-speed video cinematography to investigate how honeybees detect, pursue and intersect moving targets.

The results of his work will be applied to unmanned aerial vehicles to avoid collisions with other objects.

Professor Linda Richards secured $785,000, which will be used to gain greater understanding into how the cerebral cortex is built during embryonic life.

Profile Dr Jian Yang

Profile Dr Jian Yang

Dr Jian Yang completed his Bachelor degree in biological science at Zhejiang University, Hangzhou, China in 2003. He followed his Bachelor with a 5-year PhD in the area of statistical genetics and bioinformatics at the same university under the supervision of Professor Jun Zhu. Dr Yang’s PhD project focussed on developing statistical methods and software tools to locate gene loci influencing the phenotypic variation of quantitative traits. The methods he developed during this time have since been applied in genetic studies of crops such as rice and to the study of the genetic architecture of complex traits in model organisms such as mouse and rat.

Dr Yang relocated to Australia after receiving his PhD in 2008, when he joined Professor Peter Visscher’s laboratory at the Queensland Institute of Medical Research (QIMR). By making this move, Dr Yang shifted his research interest from plant and animal genetics to human genetics.

In 2012, he moved to The University of Queensland (UQ), still as a member of Professor Visscher’s laboratory*, to continue his work in the area of statistical genetics.

During his time at UQ, Dr Yang has received a number of prestigious awards, including the Centenary Institute Lawrence Creative Prize in 2012, which recognises young talent in medical research in Australia. In 2013, Dr Yang received a UQ Foundation Research Excellence award and was one of two recipients of the Sylvia and Charles Viertel Charitable Foundation’s Senior Medical Research Fellowship, which will provide $245,000 per year for 5 years to support his research.

Currently, Dr Yang’s research is focussed on developing new statistical methods and performing novel analyses to better understand the genetic basis of human complex diseases such as obesity and neuropsychiatric disorders. This includes quantifying the overall impact of all DNA variants on the risk to a disease, identifying individual genes or genetic variants that affect the disease, and predicting the risk of developing the disease.

Dr Yang says it is both the weather and the research atmosphere that keeps him in Australia and at UQ. He says he is intrigued by the complex nature of how DNA changes ultimately make a difference in our phenotypes.

*Professor Visscher now holds a joint appointment between UQ’s Diamantina Institute and QBI.

Scientists discover tool to understand nerve cells

Scientists discover tool to understand nerve cells

This artwork represents the use of single light stimulus on nerve cells within a C. elegans worm. Nick Valmas and Dee McGrath, for the Hilliard laboratory.

Our researchers are one step closer to understanding neurodegenerative diseases after developing a tool to explore how nerve cells become damaged.

The research team, led by Dr Massimo Hilliard, along with Dr Marc Hammarlund at Yale University and Dr Hang Lu at Georgia Institute of Technology, used a fluorescent protein named KillerRed to damage neurons in roundworms.

They then used a single light stimulus on nerve cells producing KillerRed, and the cells, in turn, generated reactive oxygen species that damage the neuron.

The tool allowed the team to study how the worm’s nerve cells responded to excessive free radicals triggered by KillerRed.

“This newly developed tool will allow us not only to investigate neuronal function, but also to understand how neurons respond to damage caused by reactive oxygen species, which are generated in several neurodegenerative diseases,” Dr Hilliard said.

“One of the best way to interrogate a neuronal circuit is to destroy some of its specific components and then study the resulting effects.

“The study showed KillerRed activation was efficient and versatile, functioning in several different neuronal types, and highly specific, leaving unharmed surrounding tissues and cells that were not expressing this molecule.”

These results might have broad implications in brain research providing valuable insights on neuronal function as well as how neurons get damaged and die.

The publication, “Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen using KillerRed”, is published in the 31 October 2013 issue of the journal Cell Reports.

Scientists shed light on brain computations

Scientists shed light on brain computations

Scientists have made a fundamental breakthrough into how the brain decodes the visual world.

The retina, a thin neuronal network located at the back of the eye, transmits visual information to the brain.

Disturbance of this network by disease, such as macular degeneration, leads to blindness.

Using advanced electrical recording techniques, it has been discovered how the output cells of the retina compute the direction that objects move in the visual world.

By making electrical recordings from retinal cells, Dr Ben Sivyer and Associate Professor Stephen Williams have uncovered the essential part that dendrites – the branched extensions of cells that receive input signals – play in decoding visual images.

“Our work over the last 10 years has shown that dendrites provide neurons with powerful processing capabilities, however, the function of dendritic processing in the real-time operation of neuronal networks has remained elusive,”
says Associate Professor Williams.

To gain greater insight, the group measured electrical activity from multiple sites in retinal ganglion cells when visual stimuli moved through space.

“The retina is an ideal system to investigate the role of active dendritic integration in neuronal circuit function because this network can be maintained intact in a dish and retains its responsiveness to natural stimuli,” he said.

Whilst it has long been known that the retinal network extracts and signals specific aspects of visual stimuli, the new work is the first to show how such responses are computed.

“We found that retinal ganglion cells compute the direction of light stimuli through exquisitely controlled local integration compartments in the dendritic tree, a finding which highlights the key function that dendrites play in brain computations,” said Associate Professor Williams.

Professor Perry Bartlett says this understanding of how the brain computes information is vital to brain research.

“Discovering how nerve cells process information is fundamental to understanding how we learn, and to developing new strategies to enhance learning in education and in disease processes in the brain,” he said.

Minister for Science, Information Technology, Innovation and the Arts, The Hon Ian Walker MP, congratulated Dr Sivyer and Associate Professor Williams on their internationally significant findings.

“This is another example of Queensland leading the world in health and medical research,” he said.

The paper, “Direction selectivity is computed by active dendritic integration in retinal ganglion cells”, is published in the 27 October issue of Nature Neuroscience.