An Honours degree is a year-long independent research project that can be done following the successful completion of a Bachelor's degree. Students spend the year in a laboratory in their chosen field conducting research and producing a thesis under the supervision of an academic staff member. An Honours degree allows students to deepen their understanding of a research topic through intensive practical work. Employers regard an Honours degree as a significant indicator of achievement and potential, and it may pave the way for entry into a Masters, MPhil or PhD program.
Students may undertake their Honours project supervised by researchers at QBI after gaining enrolment through one of the University's teaching schools. For students interested in applying for an Honours project in the neuroscience field, application can be made through the School of Biomedical Sciences (SBMS); more information about enrolment is available here.
Students approved to undertake an Honours project based at QBI must also apply directly to the Institute for building access, complete OHS training prior to commencing project work and agree to a Student Intellectual Property and Confidentiality Deed (contact QBI for more information by emailing collaborators@qbi.uq.edu.au).
Participation in an Honours project at QBI allows students to engage with and experience the rich intellectual resources and facilities of the Institute.
Current projects
Synaptic Functions
Group Leader Dr Victor Anggono v.anggono@uq.edu.au
Regulation of glutamate receptor membrane trafficking in neurons
The amino acid glutamate is the major excitatory neurotransmitter in the brain. The AMPA- and NMDA-type glutamate receptors are the principal receptors that mediate the majority of excitatory synaptic transmission in the mammalian brain. The dynamic trafficking and proper synaptic targeting of these receptors are crucial for synaptic plasticity, learning and memory. Importantly, dysregulation and aberrant trafficking of glutamate receptors have been implicated in many neurological disorders, including epilepsy, Alzheimer’s disease, schizophrenia and depression. In this project, we seek to determine the roles of glutamate receptor interacting proteins and post-translational modifications in regulating their precise membrane trafficking in mammalian central neurons.
Group Leader Dr Victor Anggono v.anggono@uq.edu.au
Epitranscriptomic regulation of neuronal plasticity
The human brain contains billion of neurons that are interconnected and highly organised into ensembles of neural circuits. The ability of neurons to modulate the number and strength of neuronal connectivity, termed synaptic plasticity, is critical during development, learning and memory. It is well established that activity-dependent gene transcription and de novo protein synthesis are required for long-term neuronal plasticity and memory consolidation. In this project, we seek to determine the role of post-transcriptional RNA methylation in shaping the transcriptomic and proteomic landscapes in neurons during synaptic plasticity.
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 Dr Zhitao Hu z.hu1@uq.edu.au
Information processing in the nervous system is essential for brain function, and is predominantly determined by communication between neurons, which is achieved by the release of neurotransmitters from synaptic vesicles (SVs) at presynaptic nerve terminals. Since Katz and his colleagues first revealed that Ca2+ triggers neurotransmitter release by stimulating ultrafast SV fusion at the presynaptic terminal, studies have been focusing on the roles of synaptotagmin proteins in SV exocytosis. Synaptotagmins comprise a large family of membrane proteins with multifunctional C2 domains (C2A and C2B). Upon binding Ca2+, the C2 domains insert into the plasma membrane, and promote SNARE-mediated membrane fusion. Loss of function of synaptotagmins leads to severe brain dysfunction, with mutations being implicated in many neurological disorders such as epilepsy, Parkinson’s disease, and neuromuscular junction disorder. Despite the work done on synaptotagmins, a number of questions remain unresolved regarding their roles in synaptic transmission. How many synaptotagmins serve as Ca2+ sensors in neurons? How do synaptotagmins trigger fusion at the molecular level? What are the functional differences between distinct synaptotagmins and what causes these differences? How do synaptotagmins cooperate in SV fusion? What are the functions of synaptotagmins in other tissues? Addressing these questions is critical to elucidate the fundamental mechanisms of brain function, and the basis of synaptotagmin-related neurological disorders. We hope you can join our lab to work on these interesting and important questions.
Neurogenesis and Neuronal Survival
Group Leader Dr Tara Walker t.walker1@uq.edu.au
Can delayed systemic selenium administration ameliorate the cognitive impairments observed in a mouse model of hippocampal stroke?
Stroke is the most common cause of long-term disability, including dementia, dyskinesia and dysmnesia and the third leading cause of death in Australia. Despite a large number of therapies for the treatment of stroke showing positive effects in the laboratory, few of these have reached the clinic. Therefore, a novel therapeutic option with an extended time window, simple administration route not requiring advanced equipment is highly desirable.
Clinical studies have revealed an inverse association between circulating levels of the dietary trace element selenium and the prevalence of stroke in humans. However, whether post-stroke selenium administration can ameliorate stroke-induced cognitive deficits was unknown. We have recently shown that dietary selenium supplementation can ameliorate the stroke-induced cognitive deficits in a mouse model of hippocampal stroke. Moreover, we found that selenium treatment immediately after stroke had a similar effect to four weeks of selenium pre-treatment. Therefore, for people with higher proneness to stroke, dietary selenium supplementation and a high circulating selenium level may be able to provide some level of protection against stroke-induced cognitive impairments. Moreover, selenium shows a promising potential as a clinical therapeutic target following stroke. From a therapeutic standpoint, if selenium treatment, in conjunction with the canonical thrombolysis drug, can lead to an improved functional outcome, this warrants further investigation. Therefore, the aim of this project is to determine the therapeutic window of post-stroke selenium administration. Using the endothelin-1-induced mouse model of hippocampal stroke, seleno-L-methionine will be systemically administered at different timepoints following stroke and histological analyses and cognitive tests will be performed to evaluate its clinical potential.
Group Leader Professor 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.
Neuronal Development and Connectivity
Group Leader 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.
Systems and Computational Neuroscience
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.
Group Leader Dr Matilde Balbi m.balbi@uq.edu.au
Closed-loop joystick navigation for mice
Refined forelimb movements are a distinctive feature of the mammalian motor system. Goal directed limb movements allow us to perform most tasks of daily living and to manipulate objects in our environment. These highly coordinated voluntary movements integrate relevant sensory inputs and motor command. Sensorimotor integration is often disrupted in neurological disorders, such as stroke. Mice are very dexterous with their forelimbs and share many kinematics features with humans.
This project aims to:
a. Further develop a miniature robotic joystick for applying force to guide or perturb mouse forepaw movements and integrate it to our automatic system.
- Program system for applying force perturbation
- Integration of miniaturized hardware and implementation of microprocessors (Arduino, Raspberry pi)
- Program a real-time processing routine and a GUI.
b. Develop a system for high-speed videos to track and quantify forelimb movements of mice, combined with simultaneous calcium imaging recordings
- Adapt the system for online tracking and closed loop applications.
- Program a real-time processing routine and a GUI.
Requirements: strong programming background preferably in Matlab or Python will be required, highly motivated, keen interest in biology and neuroscience. We encourage applications from Aboriginal and Torres Strait Islander students, LGBTIAQ+ students and others from backgrounds underrepresented in STEMM
Ageing and Dementia Research
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr 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
Prof J Goetz j.goetz@uq.edu.au
Understanding the dynamics of the blood-brain barrier in response to therapeutic ultrasound
The brain is considered to be the last frontier, both in terms of understanding how it operates and in accessing it for therapeutic intervention. Our laboratory works in both spaces: deciphering the role of key molecules and signalling pathways in Alzheimer's disease (AD) and developing novel ultrasound-based techniques to overcome the blood-brain barrier (BBB). The BBB restricts the flow of blood-borne substances into the interstitial brain space, facilitated by tight junctions between the cells that constitute the blood vessels thereby hindering paracellular transport, and a very low number of vesicles, thereby reducing transcytosis. Application of pulsed ultrasound (US) in the presence of intravenously injected microbubbles has been shown to transiently open the BBB in different model organisms. In previous studies by our laboratory, we demonstrated that delivery of ultrasound to Alzheimer's mice mice was sufficient to remove amyloid plaques and tau tangles and restore cognitive function. The study will use two-photon microscopy to investigate the dynamics of BBB opening following ultrasound treatment aided by the used of fluorescently labelled dextrans, thereby contributing to our strategies of using ultrasound as a therapy for Alzheimer's disease.
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
Unravelling how exosomes induce and propagate tau pathology
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 tau pathology in AD usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas in a pattern that suggests that neuronal interconnectivity facilitates AD progression, 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 extracellular vesicles such as exosomes or microvesicles. We have established that brains from mice with tau pathology produce tau seeds 'encapsulated' within exosomes. Furthermore, exosomes containing tau seeds can induce tau aggregation in recipient cells, and exosomes spread from neuron to neuron by hijacking endosomes. Exosomes are internalised by recipient cells via endocytosis. Consequently, tau seeds must not only be able to exit the exosomal membranes, but they must also be able to escape the endosomes in order to access cytosolic tau and induce corrupting cycles of tau aggregation. We aim to determine how exosomal tau seeds escape endosomes, and whether controlling the exosome production or traffic can halt or reduce tau pathology.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Andrew Kneynsberg a.kneynsberg@uq.edu.au
Understanding the fundamental biology of microtubule associated protein tau
Alzheimer’s disease and other neurodegenerative diseases (termed tauopathies) are characterized by the accumulation of the tau protein into identifiable brain pathologies. The role of tau in disease, however, is not well understood, nor are the functions tau in healthy neurons. In order to better understand the role of tau in disease pathophysiology, our group investigates tau’s basic cellular functions. In addition to tau regulating microtubule dynamics, tau is known to play a role in axonal trafficking, phosphotransferase activity, and protein translation through interaction with Fyn kinase. These functions require specific regulation of tau localization and activity, within the intracellular compartments of neurons. The Honours candidate will investigate tau biology, localization, and involvement in cellular functions using techniques in primary cell culture, protein biochemistry, and advanced microscopy.
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 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.
Neuroimaging
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.
Neural Circuits, Genetics and Behaviour
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.
Epigenetics, Longevity, and Molecular Biology
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.
Neuromodulation
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 Matilde Balbi m.balbi@uq.edu.au
Metabolic changes underlying neuroprotection
Ischemic conditions take a toll on the energy levels of neurons such that physiological levels of glutamate release may lead to excitotoxic damage, which is characterized by an intracellular overload of calcium that activates a series of signalling cascades that results in apoptosis. Mitochondria, as the powerhouse of cell, play a critical role in cell energy homeostasis and are thus inevitably involved in stroke- induced neuronal death.
This project aims to identify the effects of optogenetic stimulation at specific frequencies on mitochondrial calcium using mesoscale imaging in a mouse model of stroke.
Requirements: highly motivated, keen interest in biology and neuroscience. Programming background is a plus. We encourage applications from Aboriginal and Torres Strait Islander students, LGBTIAQ+ students and others from backgrounds underrepresented in STEMM.
Group Leader Dr Matilde Balbi m.balbi@uq.edu.au
Implication of cortical spreading depolarizations following stroke
Evolution of ischemic injury is frequently associated with a wave-like propagation of abnormal neural activity, termed cortical spreading depolarizations (CSD), also known as “killer waves”. CSD initiate from a pathological source and spread across the cortex, disrupting the metabolic equilibrium, and reducing blood flow. The tissue affected by CSDs undergoes a cascade of events that leads to an increased area of infarcted core. Using 2photon imaging, mesoscale imaging, optogenetics and electrophysiology we aim to understand how the occurrence of those waves can be modulated by brain stimulation and which cellular components may play a role in this modulation.
Requirements: highly motivated, keen interest in biology and neuroscience. Programming background is a plus. We encourage applications from Aboriginal and Torres Strait Islander students, LGBTIAQ+ students and others from backgrounds underrepresented in STEMM.
Depression Research
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.
Functional Neuroimaging and Brain Injury
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.
Neuronal Degeneration and Regeneration
Group Leader 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.