Honours

 Supervisor Dr Odette Leiter    o.leiter@uq.edu.au

How platelets regulate adult neurogenesis and memory in mice

Adult neurogenesis is the lifelong generation of new neurons in specialized regions of the adult brain. This process is regulated by different factors, including by changes in the blood. Adult neurogenesis decreases with age, and this decrease is associated with learning and memory deficits. Physical exercise is a strong positive stimulator of adult neurogenesis, also in aged mice, and reverses cognitive decline associated with aging. We recently identified platelets as necessary mediators of the rejuvenating effects of exercise in aged mice. However, the precise interactions mechanisms of platelets and the adult neural stem cell niche are unknown. The project will utilise different in vitro and in vivo techniques to investigate crosstalk between the blood and brain cells, including neural stem cell cultures and behavioural testing in mice. Understanding the molecular and cellular mechanisms that regulate new neuron production could help to counteract learning and memory deficits that are associated with ageing and neurodegenerative conditions.

 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 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 Nathalie Dehorter     n.dehorter@uq.edu.au  

Exploring neural stem cell dynamics in neurodevelopmental disorders

This project aims to determine how stem cells adapt their activity to environmental factors and produce future neurons in neurodevelopmental disorders such as autism and epilepsy. Even small changes in the timing, duration or number of cell cycles producing neural cells have major consequences for the mature brain. We will study the activity-dependent molecules that control stem cell proliferation and specification. This honours project will involve experiments in mice and human cell cultures, as well as electrophysiology, histology, and imaging.

Group Leader Prof Barry Dickson    b.dickson@uq.edu.au  Supervisor Dr Deniz Ertekin    d.ertekin@uq.edu.au

Neural circuits for cryptic female choice in Drosophila

Drosophila, fruit fly females can store sperm from multiple males and make active decisions about which sperm to retain or eject, biasing fertilisation towards preferred mates. This post-mating behaviour, “cryptic female choice”, provides a unique opportunity to study decision-making processes in a well-defined neural and genetic model. Our lab recently mapped the complete wiring diagram (connectome) of the Female Abdominal Ganglion (FAbG), the main neural centre controlling reproductive behaviours in Drosophila. This honours project will leverage this connectome to uncover the neural circuits that control sperm retention and ejection, providing insight into how the brain integrates internal and external cues to make reproductive decisions. You will learn and use a range of methods, such as fly genetics, behavioural experiments, histology, microscopy, and computational analysis.

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.

 Group Leader Associate Professor 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 Associate Professor Adam Walker     adam.walker@uq.edu.au  Supervisor Dr Adekunle Bademosi    a.bademosi@uq.edu.au

Investigating genetic risk variants in MND and FTD

Recent findings have indicated that in neuronal degeneration, one of the first components to be lost is the synapse. In motor neuron disease (MND) and frontotemporal dementia (FTD), the classical protein affected is TDP-43, where it is mislocalised from the nucleus to the cytoplasm. Normally TDP-43 governs RNA metabolism in the nucleus, however, this loss of nuclear presence has downstream effects on the abundance and thus function of synaptic proteins. Interestingly the genes of some of these synaptic proteins have also been found to carry variances which lower survival rates and increase disease severity in people living with MND and FTD. The potential Honours student will be investigating these gene variants using a combination of advanced microscopy tools, immunolabelling, primary cell culture, transgenic Drosophila, and biochemistry. This project will also examine how clinically identified therapeutics could alleviate the detrimental effects of these disease risk variants.

 Group Leader Associate Professor Adam Walker     adam.walker@uq.edu.au  Supervisor Dr Adekunle Bademosi    a.bademosi@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 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. 

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

Group Leader Jürgen Götz    j.goetz@uq.edu.au

Low-intensity ultrasound as a novel therapeutic modality for the delivery of genetic material into the brain

The team develops low-intensity ultrasound as a novel modality for treating diseases of the brain, it develops therapeutic antibodies and also aims to understand major disease mechanisms in transgenic mouse models of Alzheimer’s disease using techniques ranging from electrophysiology to biochemistry, histology, microscopy, behaviour analyses, transcriptomics and proteomics (e.g. Neuron 2023, PMID 36917978; Nature Rev Neurol 2016, PMID: 26891768). The team has also built a bespoke ultrasound system and is conducting a clinical trial in Alzheimer’s disease.

We have openings for two Honours projects to explore low-intensity ultrasound as a means to deliver genetic material into the brain of mice to ameliorate pathology and improve functional outcomes, with possible applications in the clinic.

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?
    

 Supervisor Prof Barry Dickson   b.dickson@uq.edu.au   Supervisor Dr Deniz Ertekin    d.ertekin@uq.edu.au

Neural circuits for cryptic female choice in Drosophila

Drosophila, fruit fly females can store sperm from multiple males and make active decisions about which sperm to retain or eject, biasing fertilisation towards preferred mates. This post-mating behaviour, “cryptic female choice”, provides a unique opportunity to study decision-making processes in a well-defined neural and genetic model. Our lab recently mapped the complete wiring diagram (connectome) of the Female Abdominal Ganglion (FAbG), the main neural centre controlling reproductive behaviours in Drosophila. This honours project will leverage this connectome to uncover the neural circuits that control sperm retention and ejection, providing insight into how the brain integrates internal and external cues to make reproductive decisions. You will learn and use a range of methods, such as fly genetics, behavioural experiments, histology, microscopy, and computational analysis.

 Supervisor Dr Itia Favre-Bulle    i.favrebulle@uq.edu.au

The effect of noradrenaline on myelin recovery in zebrafish brain

Myelin has a fundamental role in our brain as it protects neuronal axons and helps regulate information transmission. In this project we will investigate how norepinephrine facilitates or delays myelination at early stages of zebrafish development. This honours project will involve behavioural experiment in zebrafish, brain imaging and image analysis.

 Supervisor Dr Itia Favre-Bulle    i.favrebulle@uq.edu.au

Short term effects of noradrenergic system impairment in zebrafish

Degeneration of the noradrenergic system is known to contribute to clinical symptoms in Alzheimer's disease and Parkinson's disease. However, the underlying causal mechanisms remain unclear. In this project, we aim to reveal the identity of neurons involved, as well as the short term effects of their impairment to brain dynamics. Using a zebrafish line that labels the noradrenergic system specifically, we aim to ablate, partially to totally, noradrenergic neurons, record neuronal activity in the whole brain, and observe spontaneous behaviour.

This honours project will involve behavioural experiment in zebrafish, brain imaging and image analysis.

 Group Synaptic Plasticity lab of Professor Pankaj Sah   Supervisor Dr Margreet Ridder   m.ridder@uq.edu.au

Investigating gene therapeutic approaches for the treatment of motor neurone disease

MND is a neurodegenerative disease that affects the motor neurons. Part of the problem in finding effective treatments for MND is that the underlying causative processes are not fully understood and are most likely multifactorial. Our approach to treating MND does not focus on the underlying neurodegenerative mechanism but rather the resultant disruption in ion homeostasis that produces cell death. Ion homeostasis is critical to cell survival but is disrupted in motor neurons in MND, however not all motor neurons are equally affected in MND. For example, lower motor neurons that control leg and arm muscles are some of the first to degenerate, whereas those that regulate eye movement are resistant to degeneration. The reasons for this selective vulnerability are also not fully known but one likely mechanism involves intrinsic excitability. Neuron excitability and thus vulnerability are a product of the interplay between ion channels, ions and neurotransmitters. Researchers have developed tools to control neuron excitability in order to study their function in behaviour. Our project uses this same technology and has developed a unique gene therapeutic approach to reduce toxic excitability and prevent motor neuron death in a mouse model of MND (see https://www.youtube.com/watch?v=kvOYQyjvGqU). This honours project will involve behavioural experiments in mice as well as histological and imaging techniques. 

 Group Leader  Nathalie Dehorter     n.dehorter@uq.edu.au  

Studying a new biological marker for the early detection of Autism spectrum disorder

There is need for early biological measures in autism for better management of the condition. This project aims to study how a molecule represents a reliable marker of autism at birth. This honours project will involve experiments in mice and human, as well as histological and imaging techniques. 

 Group Leader  Professor Barry Dickson b.dickson@uq.edu.au   Supervisor Dr. Kai Feng     k.feng@uq.ed.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 Professor 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: Professor Geoff Faulkner      g.faulkner@uq.edu.au

Jumping genes and the mosaic brain

The brain is the most complex, and arguably still the least understood, organ in the human body.  A recent discovery in neuroscience is that the brain's DNA instructions can change during our lifespan. We are particularly interested in DNA mutations caused by mobile DNA, a type of "jumping gene". We want to know when and why these mutations occur during development, in what types of brain cells, and what their positive and negative effects are on brain function. This is a frontier area of research. To answer these challenging questions, we have established a range of cutting edge techniques, including in vivo CRISPR editing and nanopore DNA sequencing, to find mobile DNA mutations and study their effects in post-mortem brain tissue and animal models.

 Group Leader Associate Professor 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 Associate Professor Fatima Nasrallah     f.nasrallah@uq.edu.au

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

Supervisors:  Assoc Prof 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.

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

Group Leader Jürgen Götz    j.goetz@uq.edu.au

Low-intensity ultrasound as a novel therapeutic modality for the delivery of genetic material into the brain

The team develops low-intensity ultrasound as a novel modality for treating diseases of the brain, it develops therapeutic antibodies and also aims to understand major disease mechanisms in transgenic mouse models of Alzheimer’s disease using techniques ranging from electrophysiology to biochemistry, histology, microscopy, behaviour analyses, transcriptomics and proteomics (e.g. Neuron 2023, PMID 36917978; Nature Rev Neurol 2016, PMID: 26891768). The team has also built a bespoke ultrasound system and is conducting a clinical trial in Alzheimer’s disease.

We have openings for two Honours projects to explore low-intensity ultrasound as a means to deliver genetic material into the brain of mice to ameliorate pathology and improve functional outcomes, with possible applications in the clinic.

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

Identifying genes and conditions that control axonal regeneration

 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.