Honours

 Group Leader Dr Tara Walker     t.walker1@uq.edu.au

Can platelet factor 4 (PF4) reverse neurodegeneration and cognitive decline in Alzheimer’s disease?

Aging changes the adult brain at the molecular, cellular and functional levels, driving cognitive impairments and susceptibility to dementia-related neurodegenerative disorders, such as Alzheimer’s disease. Considering the rate at which the human population is aging, it is imperative to identify novel means to maintain functional integrity in the aged brain by protecting against, or even counteracting, the effects of aging. We have recently identified platelet factor 4 (PF4) as a key mediator of the rejuvenating effects of exercise on neurogenesis and age-related cognitive decline. This raises the exciting possibility that the rejuvenating effects of PF4 may extend beyond normal aging towards reversing neurogenic and cognitive decline in the context of Alzheimer’s disease. To investigate the therapeutic potential of PF4 administration on Alzheimer’s disease progression the well characterized transgenic AD mouse model APP_SWE/PS1ΔE9 (APP/PS1) will be used. PF4 or saline will be systemically administered into the lateral tail vein of 12-month-old APP/PS1 or wild-type littermate mice every 3 days for 24 days. Proliferating cells will be labelled with a single BrdU injection given immediately prior to the first PF4 injection. Hippocampus-dependent learning and memory will be examined using the Novel objection location and APA paradigms. Following behavioral testing, regenerative capacity, neurodegenerative pathology and neuroinflammation in the hippocampus will be assessed using immunohistochemistry and confocal microscopy or western blot analysis.

This project is suited for student with a background in molecular biology and/or an interest in neuroscience.

 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. 

 Group Leader Dr Dhanisha Jhaveri    dhanisha@uq.edu.au  

Investigating molecular and cellular mechanisms that promote resilience to stress-related mental health conditions

The discovery of neurogenesis (i.e. the production and integration of new neurons) in the adult mammalian brain has emerged as an unparalleled mechanism to understand how life experiences shape cellular plasticity, and in turn alter behavioural outcomes. A major focus of our lab is to understand how adult-born neurons contribute to the development of, and recovery from, stress-induced affective behaviour. Using pre-clinical models, our lab has uncovered an important role for adult-born neurons in the regulation of anxiety-like behaviour.  Recently, advanced transcriptomics approaches have identified new molecular candidates that may play critical role(s) in this mechanism of stress resilience. Our goal now is to interrogate whether and how these candidate genes contribute to stress-induced anxiety-like behaviour.

 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.

 Supervisor Dr Gabriela Bodea    g.bodea@uq.edu.au

Gene expression profiling in a mouse model of schizophrenia

Maternal immune activation (MIA), occurring due to infections during pregnancy, is associated with an increased risk of schizophrenia in offspring. However, it is unclear how MIA alters the foetal brain gene expression. This study examines how MIA dysregulates gene expression in the developing brain in ways relevant to schizophrenia-associated pathophysiology. Methods and techniques: qPCR, immunohistochemistry, in situ hybridization, microscopy. Students will have an opportunity to generate publications from their research. The project is suitable for students with a background or interest in neuroscience, molecular biology, and genetics.

Understanding neuronal diversity in the mammalian brain

The diversity of neuronal cells in the brain provides the basis for our complex behavioural and cognitive abilities, but how does neuronal diversity emerge and refine itself during life? Neuronal diversity can be grossly defined based on anatomical location, the shape and size of neurons, and the neurotransmitters or electrical signals sent by neurons. However, the neuronal diversity defined at the molecular level is much less understood. In recent years, the long-Interspersed Element 1 (LINE-1 or L1) retrotransposons have emerged as a novel source of DNA variation in the human brain. Through a copy-and-paste mechanism of mobilisation, L1 DNA sequences “jump” from one location in the genome to another location and alter neuronal genomes. Previous studies have demonstrated that L1 mobilisation is higher in neurons than in other brain cell types and this activity can occur during neuronal development. However, many fundamental features of L1 mobilisation during brain development are unknown. Our goal is to identify the cellular requirements and precise timing of L1 activation during neurodevelopment. The candidate for this project will learn various cell culture, immunohistochemical, microscopy, analysis of imaging data, as well as molecular biology techniques. The project is suitable for students with a background or interest in neuroscience, imaging, and molecular biology.

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

 Group Leader  Professor Bryan Mowry    b.mowry@uq.edu.au

The Indian Genome-Wide Association Study (GWAS) - Phase Two

The project aims to conduct GWAS of Schizophrenia using a larger sample size of an Indian cohort. The candidate would be involved in pre and post imputation GWAS quality control comprising of identifying suitable individuals (i.e. identifying sample mix-ups, gender discrepancies and population outliers) and variants for imputation and GWAS. This dataset would be part of the larger GWAS dataset comprising of in-house Indian samples and the UK Biobank Indian samples.  The student would have the opportunity to learn to use the UQ’s High-Performance Computing (HPC) platforms and high-throughput computational genomics/bioinformatics pipelines for analyses.  The results of the project will contribute to determining whether our initial statistically significant finding (from phase one Indian GWAS) will be confirmed in a larger sample.  New findings will be mostly published as journal papers and as conference abstracts when appropriate. This project will be suited for students with a computational background. However, students with non-computational backgrounds with a desire to learn and increase their computational skills, are also invited to apply.

Spatio-temporal Gene Regulation of Mouse Brain Development

There are spatio-temporal brain gene expression resources available to study the dynamics of gene expression in developing human and mouse brains. Although some human and mouse gene expression dynamics have been published, the regulatory dynamics of transcription factors (TFs) and miRNAs have not been investigated. As TFs can have a global impact on brain development, the regulatory trajectories can provide valuable insights into gene regulation of the developing brain. The project aims to compile the developed human spatio-temporal brain development dataset. A similar approach would be used to identify the regulatory trajectories of the developing mouse brain. The students would have the opportunity to learn to use the UQ’s High-Performance Computing (HPC) platforms and use data mining applications to analyse the mouse spatio-temporal brain gene expression data.

The ideal candidate will require computing and programming skills. Individuals with non-computational backgrounds with experience in computer programming, and a desire to increase their computational skills, are also invited to apply. The results of the project will be mostly published as journal papers or as conference papers when appropriate. Successful models and applications will be implemented and developed into open-source packages.

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

Supervisor 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 to unravel brain physiology under both healthy and pathological conditions. 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 expect that the results from this project will have a significant impact on our understanding of how the brain functions under healthy and pathological conditions.
 

 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.

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

Supervisor Dr Pranesh Padmanabhan  p.padmanabhan@uq.edu.au and  Supervisor Dr Gerhard Leinenga  g.leinenga@uq.edu.au

Understanding the dynamics of the blood-brain barrier in response to therapeutic ultrasound (2+ projects)

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.

One potential Honours project 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. Another project will use cell lines including optimized BBB in vitro systems to gain insight into the dynamics of BBB proteins in response to ultrasound.
 

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

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

Elucidating how exosomal and vesicle-free tau seeds induce tau pathology in Alzheimer's Disease

Alzheimer's Disease (AD) is an irreversible and progressive dementia characterised by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid, and tau. Regarding tau, a large number of studies have revealed that its pathological aggregation impairs neuronal physiology at various levels, including damage of axonal transport, action potential firing, synaptic plasticity, memory formation, nuclear transport, chromatin structure, and mitochondrial function which eventually results in neurodegeneration (Polanco et al., Nat Rev Neurol 2018). It is believed that tau pathology is induced by misfolded tau seeds that propagate transsynaptically and corrupt the proper folding of soluble tau in recipient neurons (Polanco & Götz, FEBS J 2021; Polanco et al., Acta Neuropathol Commun 2018). Tau seeds with demonstrated ability to induce tau aggregation are: (i) vesicle-free or naked tau in the form of oligomers or fibrils, and (ii) exosomal tau encapsulated by the membranes of secretory extracellular vesicles known as exosomes (Polanco et al., J Biol Chem 2016). We recently demonstrated that exosomes can deliver tau seeds into the cytosol via permeabilization of endolysosomes (Polanco et al., Acta Neuropathol 2021). My research focuses on three major lines of investigation: (i) the role of extracellular vesicles known as exosomes in the spreading and induction of Alzheimer's pathology, (ii) elucidating mechanisms by which exosomes deliver cargoes into the cytosol, and (iii) discovering genes and elucidating cellular processes that bring about tau aggregation (Briner, Götz & Polanco, Cell Rep 2020). I currently have available projects for students on the role of exosomes in AD and under physiological conditions, aiming at answering questions such as:

1. Can exosomal delivery into the cytosol be controlled or modulated?
2. What genes regulate exosomal delivery into the cytosol?
3. How to halt or reduce tau pathology by controlling exosome production or traffic?
4. What genes are important for the induction of tau aggregation?
5. What’s the functional overlap between exosomal and vesicle-free tau seeds?
6. How can pivotal genes for tau aggregation be regulated?

 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 Dr Dhanisha Jhaveri    dhanisha@uq.edu.au  

Investigating molecular and cellular mechanisms that promote resilience to stress-related mental health conditions

The discovery of neurogenesis (i.e. the production and integration of new neurons) in the adult mammalian brain has emerged as an unparalleled mechanism to understand how life experiences shape cellular plasticity, and in turn alter behavioural outcomes. A major focus of our lab is to understand how adult-born neurons contribute to the development of, and recovery from, stress-induced affective behaviour. Using pre-clinical models, our lab has uncovered an important role for adult-born neurons in the regulation of anxiety-like behaviour.  Recently, advanced transcriptomics approaches have identified new molecular candidates that may play critical role(s) in this mechanism of stress resilience. Our goal now is to interrogate whether and how these candidate genes contribute to stress-induced anxiety-like 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.

 Group Leader Dr Zhaoyu Li      zhaoyu.li@uq.edu.au

Decoding neural circuit structure and function using C. elegans as a model

Our lab ultimately seek to understand how neural network generates sensorimotor behaviour, and how dysfunction of brain network leads to behavioural deficits and disorders. Animals produce an incredible repertoire of sensorimotor behaviours to interact with the outside world. The underlying basis is synaptic connections between neurons in circuits within the nervous system.  Therefore, understanding of circuit and synaptic integration and plasticity is key to decode brain functions. By employing state-of-the-art techniques such as whole brain imaging and optogenetics, we are particularly interested in 1) how neural network integrates sensorimotor information and encodes diverse behaviours, 2) how different factors such as experience, ageing and disease reshape this process. We use C. elegans, a research model with only 302 neurons to address these questions. Honours recruited in these projects not only have opportunities to address important scientific questions in this area, but also receive systematic training in neuroscience including molecular genetics, transgenic animal generation, behavioural analysis, optogenetics and imaging. 

 Group Leader Assoc Prof Thomas Burne     t.burne@uq.edu.au  Primary Supervisor Dr James Kesby     j.kesby@uq.edu.au

The role of dopamine systems in reversal learning

Excess dopamine function is a key underlying factor in psychotic disorders such as schizophrenia. There is now also evidence that dopamine systems may also impair decision-making processes. Our work uses viral strategies to manipulate dopamine systems in mice performing complex decision-making tasks. Mice can be trained to perform a reversal learning task similar to that used in people with psychosis. Understanding the precise influence of excess dopamine function on reversal learning will help better understand what cognitive impairments in schizophrenia may results from excess dopamine function.

This project focusses on preclinical behavioural neuroscience and includes computational modelling to better identify underlying cognitive processes guiding behaviour.

 Group Leader  Professor Darryl Eyles    d.eyles@uq.edu.au

Investigating the factors that control dopamine release in an animal model of relevance to schizophrenia (EDiPs)

Increased dopamine release in the dorsal striatum is the strongest neurochemical finding in patients with schizophrenia and those at risk of developing schizophrenia. We have developed an animal model (EDiPs) in which dopamine synthesis is increased in the dorsal striatum gradually from adolescence to adulthood. Using an ex vivo preparation of the EDiPs striatum and 2-photon microscopy we intend to discover how increasing dopamine synthesis affects the release machinery in the brain. Such knowledge may inform future therapies.

Vitamin D (the sunshine hormone) increases dopamine release in the brain

We have established that vitamin D deficiency in utero is a risk factor for schizophrenia. We have also shown vitamin D deficiency affects how developing dopamine systems develop in an animal model. More recently we have described how local administration of the active vitamin D hormone in the dorsal striatum of the brain profoundly increases dopamine release. Using brains that have undergone microdialysis studies (to show this increase) we now wish to understand what possible factors vitamin D is acting on i.e. dopamine synthesis/packaging/release/breakdown/uptake? This knowledge is crucial for understanding the role of vitamin D in controlling the major neurotransmitter implicated in schizophrenia.

 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.

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

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 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.
 

Mapping the functional connectome following a concussion

Resting state functional connectivity using fMRI has become an important tool in examining differences in brain activity between patient and healthy populations. It describes interregional correlations across the brain and has gained prominence in recent years not only for its usefulness in highlighting several functional neural networks of the brain, but also for identifying neuroimaging biomarkers of a disorder.

This work will focus on understanding the functional connectome in the brain and how the temporal profile of these brain networks change over time following a concussive injury, specifically in sports-related concussion.

The candidate will gain experience in multimodality imaging methods, data analysis of imaging data, and a better understanding of the biomarkers that are related to concussion detection and prediction.
 

Probing markers of axonal injury and tissue integrity in traumatic brain injury patients using Diffusion tensor imaging

Traumatic brain injury affects a significant number of patients worldwide. The changes in the brain that provide us with sufficient information to predict patient outcomes are not known.

In this project we aim to use advanced magnetic resonance imaging (MRI), specifically diffusion tensor imaging, to determine changes in the grey and white matter of the brain to allow better interpretation of whether these changes allow for better diagnosis of injury severity and better prognostication of patient outcome.

Gained skills: The project will provide candidates with the theoretical and technical expertise relevant to multimodal MRI imaging, MRI data processing, and the software skills that would allow them to interpret the next stage of MRI data that may become the standard of care in the clinic.

Prior experience: an interest in magnetic resonance imaging and traumatic brain injury. The work would be suitable for students with a background in medicine, biomedical sciences, computational neuroscience, biomedical engineering, engineering, neuroscience or other areas of study. No prior experience in MRI imaging and data processing is required although this would be preferable and the candidate will be able to learn such skills as part of the process.
 

Blood brain barrier leakiness measured with magnetic resonance imaging following a traumatic brain injury

The blood brain barrier (BBB) is the border that protects our brain. Following a traumatic brain injury, the blood brain barrier becomes leaky and we can use magnetic resonance imaging, specifically, dynamic contrast enhanced MRI, to measure this leakiness. We have data that has been collected and is being collected to investigate ways to monitor BBB leakiness and determine whether it can predict the outcome of a patient following a traumatic brain injury.

Gained skills: The project will provide candidates with the theoretical and technical expertise relevant to multimodal MRI imaging, MRI data processing, and the software skills that would allow them to interpret the next stage of MRI data that may become the standard of care in the clinic.

Prior experience: an interest in magnetic resonance imaging and traumatic brain injury. The work would be suitable for students with a background in, but not limited to, medicine, biomedical sciences, computational neuroscience, biomedical engineering, engineering, neuroscience or other areas of study. No prior experience in MRI imaging and data processing is required although this would be preferable, and the candidate will be able to learn such skills as part of the process.

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

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

Identifying 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.

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

 Supervisor Dr Esteban Cruz Gonzalez     e.cruz@uq.edu.au

Developing therapeutic tau antibodies and understanding how they engage and clear tau

Deposition of intracellular protein aggregates of the microtubule-associated protein Tau (MAPT) are a pathogenic hallmark of a broad range of neurodegenerative disorders termed tauopathies, and are the main constituents of neurofibrillary tangles found in Alzheimer’s patients. It is now well established that patterns of tau deposition correlate well with atrophy and cognitive decline in Alzheimer’s disease (AD), pointing to the potential of developing targeted anti-Tau therapies. Among current platforms to develop targeted therapies, none match the specificity and versatility of antibodies and their derivatives, having dominated the biopharmaceutical landscape in the last two decades as a reflection of their remarkable therapeutic properties. Yet, targeting an intracellular protein like tau presents significant challenges, and several ongoing efforts in the industry have failed to provide convincing evidence of therapeutic benefit in clinical development. Our group has previously generated and characterised antibodies against tau, showing that they can ameliorate tau pathology in mouse models of tauopathy. However, the exact mechanisms through which tau antibodies exert their function is unclear, and such information is required to optimise their design. This project aims to unravel the mechanisms by which our antibodies decrease tau burden, using a combination of in vitro cell-based assays and animal models, alongside a battery of biochemical techniques to obtain a full picture of how antibodies affect relevant pathogenic processes. These insights, in conjunction with recent breakthroughs in understanding the structural properties of tau, will be harnessed to develop new optimised antibodies.