Honours

 Group Leader A/Proffessor Helen Cooper     h.cooper@uq.edu.au

The adult brain contains neural stem cells that continue to make new neurons throughout life. Research in the Cooper lab has identified signaling molecules that may be harnessed to promote the birth of new neurons and their migration to damaged regions of the brain. The development of effective endogenous stem cell-based therapeutic strategies to promote neurogenesis and migration would be a major step forward in achieving functional recovery in the damaged brain.

 

 Group Leader Professor Fred Meunier    f.meunier@uq.edu.au

The overall goal of our research is to determine how brain cells communicate and survive in health and disease. Our lab focuses on the molecular events governing vesicular trafficking within presynaptic nerve terminals and neurosecretory cells. Our discoveries have led to a deep understanding of how secretory vesicles interact with the cortical actin network on their way to fuse with the plasma membrane to release the neurotransmitter. In parallel to this process, internalisation of key neurotrophic factors occur at the synapse leading to survival. How these two trafficking pathways talk to each other is the focus of our current research. We have a range of projects available to honours looking at how molecular interactions govern trafficking events in synapse leading to both neurotransmission and survival. 

 Group Leader Professor Linda Richards     richards@uq.edu.au

Human agenesis of the corpus callosum, autism spectrum disorder and brain wiring

Agenesis of the corpus callosum is a brain wiring alteration that occurs during brain development.  Many people have some characteristics that are similar to those with autism spectrum disorder. We are investigating brain wiring connectivity using high-field magnetic resonance imaging and neuropsychological testing to understand how brain connectivity underpins the function of the brain. We also want to understand the underlying causes of agenesis of the corpus callosum by performing genetic analyses of DNA from people with these disorders compared to controls.  The work will have a significant impact on our understanding of how changes in brain wiring impact brain function.

Opportunities exist for students with a background or interest in:  Neuroscience, genetics, magnetic resonance imaging and physics, neuropsychology, medicine, computer science (data analysis and software development).

Function of genes and molecules in agenesis of the corpus callosum and brain developmental disorders

Identifying a causal genetic mutation in a person requires functional studies to determine if the mutation causes a change in the function of the gene. This work requires in-depth analysis in animal models to examine gene function in cellular proliferation, differentiation, migration and cortical wiring. We are interested to understand the basic mechanisms regulating these developmental events and hwo they are altered in human brain disorders including agenesis of the corpus callosum, ventriculomegaly, hydrocephalus and cortical malformations. This work has a significant translational impact on understanding the causes of brain developmental disorders.

Opportunities exist for students with a background or interest in:  Neuroscience, genetics, cell biology, developmental biology, glial development, animal behaviour, medicine.

The function of early neuronal activity on the formation of neocortical circuits

How does the brain acquire its connectivity pattern during development? This project aims at elucidating the main roles of early sensory and spontaneous activity in the formation of neocortical circuits. By combining molecular, electrical and developmental manipulations in developing mammalian embryos and pups, this project will study how early events affect the precise formation of cortical features required for normal cognitive development. The work will have a significant impact on our understanding of how the brain is wired for function.

Opportunities exist for students with a background or interest in:  Neuroscience, developmental neurobiology, neurophysiology, electrophysiological signal analysis and/or computational sciences, mathematical modelling, medicine.

Principles of neural development applied to understanding brain cancer

Brain cancer is a significant health problem in Australia. One of the most aggressive forms of brain cancer is glioblastoma (GBM) and the prognosis for these patients is extremely poor. What is needed is a deeper understanding of the cause of brain cancer. We are approaching this challenge by utilising the principles of neural development to understand how tumours first arise in the brain and how they are able to continue to grow and metastasize in order to find the causes and treatments for adult and pediatric brain cancers that originate from glia. Nuclear factor one (NFI) genes have been implicated in brain cancer and in glial development. We have generated a number of animal models of Nfi gene mis-expression to determine the function of NFI genes in brain cancer. This work will have a significant impact on our understanding of the cause and progression of brain cancer.

Opportunities exist for students with a background or interest in:  Neuroscience, genetics, cell biology, developmental biology, glial development, animal behaviour, medicine.

 

 Group Leader Associate Professor Massimo Hilliard     m.hilliard@uq.edu.au

Identifing genes and conditions that control axonal regeneration

How neurons can maintain their axonal structure and function over time is not well understood. Axonal degeneration is a critical and common feature of many peripheral neuropathies, neurodegenerative diseases and nerve injuries. The genetic factors and the cellular mechanisms that prevent axonal degeneration under normal conditions and that trigger it under pathological ones are still largely unknown. We aim to use C. elegans genetics to identify the molecules and the mechanisms that control these processes.

Identifing molecules and mechanisms of axonal degeneration

How some axons can regenerate after nerve damage while others cannot is a crucial question in neurobiology, and the answers will be of great value for the medical handling of neurodegenerative diseases and of traumatic nerve injuries. Largely unknown are the molecules and the mechanisms underlying this important biological process. In C. elegans, a new laser-based technology allows single neuron axotomy in living animals, and axonal regeneration can now be visualised in real-time and tackled with a genetic approach. Our goal is to identify the genes and conditions that control this fascinating process.

 

 Group Leader Associate Professor Helen Cooper     h.cooper@uq.edu.au

Investigating the mutations in genes that impact cortical development

The intricate neural architecture of the 6-layered mammalian neocortex is dependent on the ability of neural stem cells to differentiate into new neurons. These young neurons must then migrate into the correct cortical layers. In humans, mutations in genes controlling these processes have severe consequences for cortical development leading to intractable epilepsy, mental retardation, schizophrenia, dyslexia and autism.

Identifing molecular targets for axon regrowth

The corpus callosum is the major axon tract connecting the left and right hemispheres in the human neocortex. There are more than 50 different human congenital syndromes, often associated with mental retardation and epilepsy, in which this axon tract fails to develop. This project aims to identify molecular targets that can be manipulated to encourage axon regrowth and correct pathfinding in the damaged human brain and spinal chord.

 

 Group Leader Professor Geoffrey Goodhill     g.goodhill@uq.edu.au

Investigating the rules developing axons use to respond to both single and multiple molecular guidance cues

We are developing new microfluidic gradient technologies to investigate the rules developing axons use to respond to both single and multiple molecular guidance cues. This project is suitable for students with a strong biology or bioengineering background. Experience in tissue culture would be advantageous. For more details about the lab see cns.qbi.uq.edu.au.

 Group Leader Professor Geoffrey Goodhill     g.goodhill@uq.edu.au     cns.qbi.uq.edu.au

How neurons in the zebrafish brain code visual activity

We are performing experiments to determine how neurons in the zebrafish visual code information about the world, and how this neural activity is correlated with their behaviour. Projects are available in the experimental or computational aspects of this project. The experimental side is suitable for students who would like to learn state-of-the-art methods for brain imaging and/or behavioural analysis. The computational side involves advanced methods in image processing, statistical modelling and mathematical theories of neural coding, and is suitable for mathematics, physics, engineering or computer science students, particularly those with a strong programming background. 

How growing nerve fibres find their targets in the developing brain

We are performing experiments to determine how growing nerve fibres find their targets in the developing brain. The experimental side is suitable for students who would like to learn state-of-the-art methods for culturing nerve cells. The computational side involves advanced methods in image processing and statistical modelling, and is suitable for mathematics, physics, engineering or computer science students, particularly those with a strong programming background.

 Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz

  Dr J Liviu Bodea  l.bodea@uq.edu.au

Characterisation of novel animal models generated by CRISPR technology

Our lab has a long-standing history of generating different animal models helpful for the understanding of the brain physiology under both healthy and pathological conditions. Recently, we have applied CRISPR-based cutting-edge genomic approaches to generate several animal models targeting different molecules important for brain function or neurodegenerative progression. The student candidate will analyse these models under the guidance of Dr. Liviu Bodea. We expecting that the results from this project will have a significant impact on our understating of how the brain is functioning in healthy or pathological conditions.

Requirements: interest in neuroscience, tissue processing and imaging techniques

Identification of changes in the brain's molecular composition in response to the environment

Brain molecular composition is dynamic, with the surrounding environment being one of the most important elements affecting it. Based on our tools designed to identify and isolate different cell types from the brains of animals undergoing behavioural tasks, the student candidates will investigate these molecular-level changes in the brain under the guidance of Dr. Liviu Bodea. This work will provide important advancements in our understanding of brain’s response to the environment at the molecular level.

Requirements: interest in neuroscience, tissue processing and imaging, behavioural techniques

Developing CRISPR based in vitro tools

Simplistically, normal cellular functions are based on intracellular signalling that rely in turn on interactions between particular proteins. To be able to study these functions, either a genetic of pharmacologic approach is applied to alter one of these proteins and investigate its effect. The recent advances in CRISPR-based genome editing opened the possibility of fast and targeted introduction of proteins modification. During this project, the candidate will work under the guidance of Dr. Liviu Bodea to generate in vitro mutants using cutting-edge CRISPR-based techniques. The tools generated in this project will significantly enrich and update the available toolset useful to study brain’s functions.

Requirements: interest in genetics and cell culture hands-on techniques

 

 Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz

  Dr Rebecca Nisbet  r.nisbet@uq.edu.au

Improving motor or memory function with active and passive immunisation

Ongoing clinical trials in Alzheimer's disease employ both active and passive immunization approaches targeting the toxic peptide amyloid-beta. We have shown recently, that the intracellular protein tau is also a suitable target for therapeutic intervention, using FTD tau transgenic mouse models. By active and passive immunisation of FTD mutant tau transgenic mouse models we have shown that this results in an improvement using biochemical and histological read-outs. However, we failed to achieve an improvement in motor or memory functions. To achieve this goal we are currently developing single chain antibodies. Moreover, because tau is aggregating intracellularly, we are developing these antibodies further to use them as intrabodies. For delivery we will use both viral vectors and focused ultrasound.

 

 Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz

  Dr J Chuanzhou Joe Li  c.li8@uq.edu.au

Assessing the structural changes in the spine

The protein tau and the peptide Abeta form the two key lesions in the Alzheimer brain, the neurofibrillary tangles and the amyloid plaques. Tau is essential for Abeta to mediate its toxic effects including excitotoxic signaling. This project will assess the structural changes in the spine that make mice in which the interaction of NMDAR and PSD95 has been transiently disrupted permanently resistant to Abeta toxicity. The project will further address the role of these interactions in learning and memory using transgenesis and complementary mouse and C. elegans models. - Basic expertise in biochemistry and molecular biology techniques is required, while some experience in animal experimentation (including behaviour), biochemistry techniques including western blotting, and histology would be advantageous.

 

 Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz

  Dr Juan Carlos Polanco  j.polanco@uq.edu.au

Are nanovesicles isolated from AD transgenic toxic and do they elicit an AD pathomechanism in recipient cells

Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid and TAU. The AD pathology usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas. AD progression is characterized by increasing TAU aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via nanovesicles such as exosomes or microvesicles. Using AD mouse models with Tau overexpression, we found that Tau transgenic mice have indeed nanovesicles that contain TAU protein. This project is about the characterization of these nanovesicles and the question whether nanovesicles isolated from AD transgenic are toxic and elicit an AD pathomechanism in recipient cells.

 

 Group Leader Professor Fred Meunier     f.meunier@uq.edu.au

How brain cells communicate and survive in health and disease

The overall goal of our research is to determine how brain cells communicate and survive in health and disease. Our lab focuses on the molecular events governing vesicular trafficking within presynaptic nerve terminals and neurosecretory cells. Our discoveries have led to a deep understanding of how secretory vesicles interact with the cortical actin network on their way to fuse with the plasma membrane to release the neurotransmitter. In parallel to this process, internalisation of key neurotrophic factors occur at the synapse leading to survival. How these two trafficking pathways talk to each other is the focus of our current research. We have a range of projects available to honours looking at how molecular interactions govern trafficking events in synapse leading to both neurotransmission and survival. 

 

 Group Leader Dr Rodrigo Medeiros Neurula lab     r.medeiros@uq.edu.au

Role of the immune system in neurodegeneration

Dr Medeiros discovered that Alzheimer's disease promotes defects in fundamental molecular events that limit and resolve inflammation, and demonstrated that such changes account for a substantial portion of the disease pathogenesis. Currently, the Neurula lab is undertaking the challenge of using and developing novel laboratory models in parallel with studies on affected human subjects to elucidate the underlying molecular mechanisms linking inflammation to β-amyloid, tau pathology and cognitive decline. Understanding these mechanisms will allow definition of the biological pathways involved in the onset and progression of Alzheimer’s disease, and identify potential therapeutic targets for the management of this devastating disorder.

Impact of comorbidities in brain ageing and disease

The Neurula Lab also studies the impact of comorbidities in neurodegeneration and Alzheimer’s disease. We seek to understand how concurrent diseases that commonly occur in the elderly may modulate neurodegeneration and age-related changes in the brain. We have been particularly interested in infections, diabetes and traumatic brain injury as major regulators of biological processes, and are developing genetic and pharmacological agents to manipulate these pathways in Alzheimer’s disease.

 

 Group Leader Dr Fatima Nasrallah     f.nasrallah@uq.edu.au

The relationship between traumatic brain injury and Alzheimer's disease in a transgenic mouse model

Supervisors:  Dr Fatima Nasrallah and Dr Rodrigo Medeiros.

Traumatic brain injury (TBI) is considered as one of the strongest epigenetic risk factors for developing dementia, specifically Alzheimer’s disease (AD). TBI has been shown to fastforward the onset of AD by more than 4 years on average and while it is unclear the mechanism by which TBI leads to early onset of AD symptoms and sever cognitive decline, a history of moderate TBI results in a 2.3 times greater risk of developing AD while a history of severe TBI results in a 4.5 times greater risk. To understand the underlying mechanism and link between TBI and AD, we will investigate molecular and immunohistochemical markers of AD, mainly neurofibrillary tau tangles, amyloid plaques, and neuroinflammatory markers in a ALZ17 transgenic mouse model following a TBI. The study will allow us to determine the role of neuroinflammation in the process following TBI and how much that has an effect on the tau and amyloid buildup in the brain in AD. The candidate for this project will learn various immunohistochemical and molecular wet lab methods and will also have the opportunity to learn data processing of magnetic resonance imaging data that is available for these cohort of mice. If interested, please email f.nasrallah@uq.edu.au for more information.

 

 Group Leader Dr Adam Walker     adam.walker@uq.edu.au

Understanding the earliest disease mechanisms in MND and dementia

Motor neuron disease (MND) and frontotemporal dementia (FTD) are both fatal neurodegenerative diseases, which are characterised by aggregation of a protein known as TDP-43 within neurons. In screening experiments, we have identified hundreds of proteins that are altered very early in disease in genetically modified TDP-43 mice. We have several projects in which you will investigate changes in protein levels and sub-cellular localisation of several of our top-priority targets over time, in brains and spinal cords from these TDP-43 mice. You may also investigate TDP-43 aggregation and mislocalisation in cell lines and primary neurons, using CRISPR gene knockout and plasmid/lentiviral-mediated over-expression studies, and in vivo in the TDP-43 mice, using drugs and viruses. These projects will help identify the molecular mechanisms involved in TDP-43 malfunction and to understand new potential therapeutic targets for MND and FTD.

 

 Group Leader Associate Professor Kai-Hsiang Chuang     k.chuang@uq.edu.au

The laboratory aims to identify neuro-endophenotype of brain functions and disorders to improve our understanding of cognitive functions and disease processes, so as to facilitate diagnosis, prognosis and intervention. Neuroimaging, such as functional magnetic resonance imaging (fMRI), is a powerful tool that can map structural, functional and connectomic changes of the brain noninvasively. As the same technique can be applied in both humans and animals, it allows direct translation of findings in animal models to humans, or vice versa. We will use animal models to determine behaviour- or pathology-specific biomarkers and translate that to human.

Imaging brain connectome of rodent models of diseases

Neurodegenerative diseases, such as dementia, are irreversible and generally incurable and hence early detection is essential so that interventions can be applied to slow down its progression. Various diseases have been found to affect brain connectivity in disease-specific pattern, however the mechanisms are still unclear. We focused on characterising the change of brain connectome using MRI techniques for mapping structural and functional connectivity in mouse models and humans in vivo. This project will evaluate the effects of disease-associated risk genes or treatments on the brain connectome in transgenic mouse models of neurodegenerative diseases, such as Alzheimer’s disease, Huntington disease, frontotemporal dementia and amyotrophic lateral sclerosis, to improve our understanding of the genetic effects on the pathogenesis in human.

Imaging brain disorders and treatment response

Various pathogenic factors could contribute the altered neural structure and function in brain disorders. This project will identify brain disorder-related changes in patients using multimodal MRI and use them as biomarkers for assessing the treatment. In particular, we will track the structural and functional connectivity before and after the intervention and correlated with blood biomarkers and behaviour to understand the pathological effects of inflammation, amyloid plaque, cerebrovascular and metabolic dysfunction on the disease progression and the efficacy of intervention.

Understand neural basis of resting-state network

An interesting phenomenon of the brain is that certain brain areas form synchronous low frequency oscillation during the resting state. These resting-state networks can be detected by functional MRI (fMRI) noninvasively and their changes have been associated with attention, learning, memory and disorders. While widely applied, the neural basis of resting-state fMRI is largely unknown. We aim to understand the neural basis underlies the resting-state networks, the axonal connectivity that supports the network topology and their relevance to behaviour, such as learning and memory. We will apply fMRI in rodent under pharmacological and behaviour manipulations and validated by electrophysiology, neuronal tract tracing, lesion and optogenetics to determine the neural underpinning of the fMRI signal oscillation and its relationship with particular neural pathway and transmission system.

Techniques you will learn in our group may include: functional MRI, diffusion tensor imaging (DTI), image processing, neuroanatomy, brain function

 

 Group Leader Associate Professor Margie Wright     margie.wright@uq.edu.au

Our laboratory uses brain imaging (MRI: Magnetic Resonance Imaging) to study developmental brain changes that occur from late childhood into the teenage years and how changes in the brain relate to differences in cognitive and emotional functioning. Data are collected in twin pairs to assess both familial and environmental influences. In addition, we collect a broad range of phenotypes in order to examine their impact on development (including pubertal status, peer and family factors, sleep quality, early life factors, socio-economic status).

Opportunities exist for students with a background or interest in: neuroscience, magnetic resonance imaging, neuropsychology, mental health.

White Matter Microstructure in Adolescence

Adolescence represents a key period of human brain development. Studies have shown considerable changes in white matter microstructure during adolescence; however, studies have typically focused on age-related rather than puberty-related effects. Using high quality brain scans collected in a sample of young adolescents (9-12 years of age), this project aims to identify changes in white matter microstructure (e.g. fractional anisotropy, mean diffusivity) associated with pubertal stage.

Amygdala Volume and Anxiety Traits in Young Adolescents

There is a substantial literature suggesting a role for the amygdala in emotional processing, and further, amygdala vulnerability to negative environment. However, associations between amygdala volume, anxiety, and negative environmental factors, remain unclear and understudied. Adolescence is a developmental period of particular interest given adolescent vulnerability to adverse events and the increasing emergence of stress-related psychopathologies. This project will explore relationships between amygdala volume (including amygdala subfields) and anxiety traits in young adolescent twins aged 9-12 years. The effects of sex, age, and pubertal status, as well as the influence of adverse events, will be examined.

Hippocampal Volume and Cognitive Function in Young Adolescents

The hippocampus is a subcortical structure posited to mediate cognitive processes. During adolescence, maturational changes are found for both hippocampal volume and cognitive performance. This project will investigate relationships between hippocampal subfield volumes and ability on a range of cognitive traits in young adolescents aged 9-12 years. In addition to age, sex differences and the influence of pubertal stage will be explored.

 Group Leader  Professor Barry Dickson b.dickson@uq.edu.au    Dr. Kai Feng     k.feng@uq.edu.au

Neural mechanisms underlying locomotion

As animals walk, run, or hop, motor circuits in the spinal cord convert descending "command" signals from the brain into the coordinated movements of many different leg muscles. How are command signals from the brain deconvolved into the appropriate patterns of motor neuron activity? We aim to answer this question for Drosophila by studying the functional organization of leg motor circuits in the ventral nerve cord, the fly’s analogue of the spinal cord. In Drosophila, individual neuronal cell types can be reproducibly identified and manipulated using genetic reagents that have been developed to target specific descending neurons, interneurons, or motor neurons. We have also established imaging pipeline to identify novel neurons that are behaviourally relevant and probe how they talk to each other. A range of projects involving optogenetics, two-photon imaging, machine learning assisted behavioural analysis and circuit modelling are currently open to honours students with a background in any area of molecular biology or experimental or theoretical neuroscience.

 Group Leader Dr Steven Zuryn     s.zuryn@uq.edu.au

Discovering epigenetic pathways that ensure robust cell function in during ageing and age-related diseases

When cells are faced with stress associated with ageing and disease, what rapid epigenetic response mechanisms help to preserve precise cell function? This is an especially relevant question in an age where neurodegenerative diseases are reaching epidemic proportions. We aim to identify and characterise epigenetic pathways that serve to protect cells, such as neurons and muscle cells, from the types of cellular stresses associated with disease by using powerful molecular genetic approaches in C. elegans. Because mitochondria are intimately linked with both ageing and age-related diseases, we focus on stress caused by damage to the mitochondria’s own genome.

 

Uncovering the secrets of the mitochondria genome in C. elegans

Originating from an ancient endosymbiotic relationship, mitochondria possess their own genome – separate to the nucleus – and assume central cellular functions. How mitochondria and their genome behave in specific tissue and cellular contexts remains a challenging question in neurobiology. We have developed novel tools (published recently in Nature Cell Biology) to address this problem in the powerful genetic model organism, C. elegans. We aim to determine how quality control of the mitochondrial genome is regulated and how deregulation may lead to disease and ageing.

 Group Leader Dr Susannah Tye    s.tye@uq.edu.au

Therapeutic mechanisms of deep brain stimulation in a progressive model of Parkinson’s Disease

The full potential of deep brain stimulation (DBS) remains untapped due to our limited knowledge of its therapeutic mechanisms. Novel stimulation protocols that target disease-specific pathological mechanisms have immense potential to improve neural and behavioural responses to directly impact clinical outcomes. This project will quantify the progressive effects of DBS on neural function and behaviour in a rodent model of Parkinson’s Disease (PD), while simultaneously examining the impact of burst stimulation relative to conventional continuous high frequency parameters. High-titer AAV serotype 8 will be used to induce alpha-synuclein (α-syn) expression in substantia nigra pars compacta (SNc) in Sprague Dawley rats to establish a model of PD with progressive loss of dopaminergic neurons in this region. DBS electrodes will be bilaterally implanted into the subthalamic nucleus (STN) following 4 weeks of exposure to α-syn and animals will be allowed 1 week to recover. Sham (no stimulation), chronic high frequency (130 Hz), intermittent burst stimulation, α-syn control, and untreated animals (n=10) will be compared following acute (1 week)of DBS treatment. Following stimulation, animals will undergo behavioural tests, imaging and then will be euthanized for post-mortem cellular and molecular analyses.

 

 Group Leader Dr Susannah Tye    s.tye@uq.edu.au

Antidepressant actions of selective inhibition of soluble tumor necrosis factor alpha in antidepressant resistant rats

In rats, chronic treatment with adrenocorticotropic hormone (ACTH) induces a state of antidepressant treatment resistance. The current study will quantify the antidepressant and anxiolytic actions of pharmaceutical agent XPro1595, a soluble TNF-alpha inhibitor, in ACTH- and saline-treated rats. The Effort-Related Reward Behaviour (ERR) task will be used as a measure of anhedonia to determine the antidepressant effects of treatment. This paradigm is designed to test the effort a subject is willing to expend in order to obtain a reward and is sensitive changes in dopamine neurotransmission. Changes in behavioural responses will be determined together with measures of inflammatory markers, dopamine neurotransmitter levels and dopamine receptor expression in the brain.