Honours
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 paves the way for entry into a Masters or PhD program.
Students may undertake their Honours project supervised by researchers at QBI; however, enrolment must be gained through one of the University's teaching schools. Participation 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
The role of BAR domain containing proteins in controlling synaptic vesicle recycling
Neurotransmitters are packaged inside synaptic vesicles within axonal terminals. A typical nerve terminal contains a small number of vesicles, only enough to maintain about 5-10 seconds of neurotransmission. Thus, synaptic vesicle membrane proteins and lipids must be retrieved and recycled by endocytosis in order to maintain the fidelity of synaptic transmission. In this project, we will investigate roles of BAR domain containing proteins in controlling synaptic vesicle recycling and how their functions are modulated by the rapid and reversible post-translational modifications, such as protein phosphorylation and ubiquitination.
Regulation of membrane trafficking of AMPA receptors
The amino acid glutamate is the major excitatory neurotransmitter in the brain. The AMPA-type glutamate receptors are the principal receptors that mediate the fast excitatory synaptic transmission in the mammalian brain. The dynamic trafficking and proper synaptic targeting of AMPA receptors are crucial in determining the strength and plasticity of excitatory synaptic transmission. In this project, we seek to determine the roles of novel AMPA receptor interacting proteins and post-translational modifications in regulating the precise membrane trafficking of AMPA receptors in mammalian central neurons.
Group Leader Professor Fred Meunier f.meunier@uq.edu.au
The overall goal of our research is to determine how brain cells communicate and survive in health and disease. Our lab focuses on the molecular events governing vesicular trafficking within presynaptic nerve terminals and neurosecretory cells. Our discoveries have led to a deep understanding of how secretory vesicles interact with the cortical actin network on their way to fuse with the plasma membrane to release the neurotransmitter. In parallel to this process, internalisation of key neurotrophic factors occur at the synapse leading to survival. How these two trafficking pathways talk to each other is the focus of our current research. We have a range of projects available to honours looking at how molecular interactions govern trafficking events in synapse leading to both neurotransmission and survival.
Group Leader Professor Joe Lynch j.lynch@uq.edu.au
Using artificial GABAergic synapses to measure defective synaptic currents
Epilepsy is a common neurological disorder that is often managed using drugs (e.g., benzodiazepines) that target the GABA type-A receptor (GABAAR) Cl channel. These receptors mediate inhibitory neurotransmission in the brain and some forms of human epilepsy arise from hereditary mutations to GABAARs. To advance our understanding of epileptogenesis, it is necessary to understand exactly how these mutations affect the function of inhibitory GABAergic synapses. Due to the large number of possible GABAAR isoforms, it is not possible to characterise the mutant synaptic receptors in vitro. The aim of this project is to investigate how GABAergic synaptic currents are affected by the epilepsy-causing GABAAR mutations. The project will employ ‘artificial’ GABAergic synapses containing defined GABAAR subunits and will measure the defective synaptic currents by patch-clamp electrophysiology. High-resolution microscopy will also be used to monitor receptor mobility in the synapse.
Investigating the effects of a variety of newly discovered startle mutations on GlyR function and expression
Glycine receptor (GlyR) chloride channels mediate fast inhibitory neurotransmission in the spinal cord and brainstem. Hyperekplexia (or startle disease) is a rare neurological disorder characterized by exaggerated startle responses to unexpected stimuli. It is caused by hereditary mutations to GlyR genes. The mutations alter GlyR function or expression efficiency, thereby leading to the disorder. The project will investigate the effects of a variety of newly discovered startle mutations on GlyR function and expression. The project will employ ‘artificial’ glycinergic synapses containing defined GlyR subunits and will measure the defective synaptic currents by patch-clamp electrophysiology. The project will provide insights into the development and function of glycinergic synapses.
Group Leader Dr Victor Anggono v.anggono@uq.edu.au
The role of BAR domain containing proteins in controlling synaptic vesicle recycling
Neurotransmitters are packaged inside synaptic vesicles within axonal terminals. A typical nerve terminal contains a small number of vesicles, only enough to maintain about 5-10 seconds of neurotransmission. Thus, synaptic vesicle membrane proteins and lipids must be retrieved and recycled by endocytosis in order to maintain the fidelity of synaptic transmission. In this project, we will investigate roles of BAR domain containing proteins in controlling synaptic vesicle recycling and how their functions are modulated by the rapid and reversible post-translational modifications, such as protein phosphorylation and ubiquitination.
Regulation of membrane trafficking of AMPA receptors
The amino acid glutamate is the major excitatory neurotransmitter in the brain. The AMPA-type glutamate receptors are the principal receptors that mediate the fast excitatory synaptic transmission in the mammalian brain. The dynamic trafficking and proper synaptic targeting of AMPA receptors are crucial in determining the strength and plasticity of excitatory synaptic transmission. In this project, we seek to determine the roles of novel AMPA receptor interacting proteins and post-translational modifications in regulating the precise membrane trafficking of AMPA receptors in mammalian central neurons.
Group Leader Professor Fred Meunier f.meunier@uq.edu.au
The overall goal of our research is to determine how brain cells communicate and survive in health and disease. Our lab focuses on the molecular events governing vesicular trafficking within presynaptic nerve terminals and neurosecretory cells. Our discoveries have led to a deep understanding of how secretory vesicles interact with the cortical actin network on their way to fuse with the plasma membrane to release the neurotransmitter. In parallel to this process, internalisation of key neurotrophic factors occur at the synapse leading to survival. How these two trafficking pathways talk to each other is the focus of our current research. We have a range of projects available to honours looking at how molecular interactions govern trafficking events in synapse leading to both neurotransmission and survival.
Group Leader Professor Joe Lynch j.lynch@uq.edu.au
Using artificial GABAergic synapses to measure defective synaptic currents
Epilepsy is a common neurological disorder that is often managed using drugs (e.g., benzodiazepines) that target the GABA type-A receptor (GABAAR) Cl channel. These receptors mediate inhibitory neurotransmission in the brain and some forms of human epilepsy arise from hereditary mutations to GABAARs. To advance our understanding of epileptogenesis, it is necessary to understand exactly how these mutations affect the function of inhibitory GABAergic synapses. Due to the large number of possible GABAAR isoforms, it is not possible to characterise the mutant synaptic receptors in vitro. The aim of this project is to investigate how GABAergic synaptic currents are affected by the epilepsy-causing GABAAR mutations. The project will employ ‘artificial’ GABAergic synapses containing defined GABAAR subunits and will measure the defective synaptic currents by patch-clamp electrophysiology. High-resolution microscopy will also be used to monitor receptor mobility in the synapse.
Investigating the effects of a variety of newly discovered startle mutations on GlyR function and expression
Glycine receptor (GlyR) chloride channels mediate fast inhibitory neurotransmission in the spinal cord and brainstem. Hyperekplexia (or startle disease) is a rare neurological disorder characterized by exaggerated startle responses to unexpected stimuli. It is caused by hereditary mutations to GlyR genes. The mutations alter GlyR function or expression efficiency, thereby leading to the disorder. The project will investigate the effects of a variety of newly discovered startle mutations on GlyR function and expression. The project will employ ‘artificial’ glycinergic synapses containing defined GlyR subunits and will measure the defective synaptic currents by patch-clamp electrophysiology. The project will provide insights into the development and function of glycinergic synapses.
Neurogenesis and Neuronal Survival
Group Leader Dr Michael Piper m.piper@uq.edu.au
How SCO development is coordinated during embryogenesis
The subcommissural organ (SCO) is a small secretory organ located in the diencephalon that plays an important role in maintaining the flow of cerebrospinal fluid from the third to the fourth ventricles of the brain. Defects to SCO development have been linked to disorders such as congenital hydrocephalus. Despite its importance, our understanding of the molecular determinants regulating SCO development remain limited. In this project we will investigate how SCO development is co-ordinated during embryogenesis, with a particular emphasis on the role played by one group of transcription factors in particular, the NFI family.
Group Leader A/Proffessor Helen Cooper h.cooper@uq.edu.au
The adult brain contains neural stem cells that continue to make new neurons throughout life. Research in the Cooper lab has identified signaling molecules that may be harnessed to promote the birth of new neurons and their migration to damaged regions of the brain. The development of effective endogenous stem cell-based therapeutic strategies to promote neurogenesis and migration would be a major step forward in achieving functional recovery in the damaged brain.
Group Leader Professor Fred Meunier f.meunier@uq.edu.au
The overall goal of our research is to determine how brain cells communicate and survive in health and disease. Our lab focuses on the molecular events governing vesicular trafficking within presynaptic nerve terminals and neurosecretory cells. Our discoveries have led to a deep understanding of how secretory vesicles interact with the cortical actin network on their way to fuse with the plasma membrane to release the neurotransmitter. In parallel to this process, internalisation of key neurotrophic factors occur at the synapse leading to survival. How these two trafficking pathways talk to each other is the focus of our current research. We have a range of projects available to honours looking at how molecular interactions govern trafficking events in synapse leading to both neurotransmission and survival.
Group Leader Dr Michael Piper m.piper@uq.edu.au
How SCO development is coordinated during embryogenesis
The subcommissural organ (SCO) is a small secretory organ located in the diencephalon that plays an important role in maintaining the flow of cerebrospinal fluid from the third to the fourth ventricles of the brain. Defects to SCO development have been linked to disorders such as congenital hydrocephalus. Despite its importance, our understanding of the molecular determinants regulating SCO development remain limited. In this project we will investigate how SCO development is co-ordinated during embryogenesis, with a particular emphasis on the role played by one group of transcription factors in particular, the NFI family.
Group Leader A/Proffessor Helen Cooper h.cooper@uq.edu.au
The adult brain contains neural stem cells that continue to make new neurons throughout life. Research in the Cooper lab has identified signaling molecules that may be harnessed to promote the birth of new neurons and their migration to damaged regions of the brain. The development of effective endogenous stem cell-based therapeutic strategies to promote neurogenesis and migration would be a major step forward in achieving functional recovery in the damaged brain.
Group Leader Professor Fred Meunier f.meunier@uq.edu.au
The overall goal of our research is to determine how brain cells communicate and survive in health and disease. Our lab focuses on the molecular events governing vesicular trafficking within presynaptic nerve terminals and neurosecretory cells. Our discoveries have led to a deep understanding of how secretory vesicles interact with the cortical actin network on their way to fuse with the plasma membrane to release the neurotransmitter. In parallel to this process, internalisation of key neurotrophic factors occur at the synapse leading to survival. How these two trafficking pathways talk to each other is the focus of our current research. We have a range of projects available to honours looking at how molecular interactions govern trafficking events in synapse leading to both neurotransmission and survival.
Neuronal Development and Connectivity
Group Leader Professor Linda Richards richards@uq.edu.au
Human agenesis of the corpus callosum, autism spectrum disorder and brain wiring
Agenesis of the corpus callosum is a brain wiring alteration that occurs during brain development. Many people have some characteristics that are similar to those with autism spectrum disorder. We are investigating brain wiring connectivity using high-field magnetic resonance imaging and neuropsychological testing to understand how brain connectivity underpins the function of the brain. We also want to understand the underlying causes of agenesis of the corpus callosum by performing genetic analyses of DNA from people with these disorders compared to controls. The work will have a significant impact on our understanding of how changes in brain wiring impact brain function.
Opportunities exist for students with a background or interest in: Neuroscience, genetics, magnetic resonance imaging and physics, neuropsychology, medicine, computer science (data analysis and software development).
Function of genes and molecules in agenesis of the corpus callosum and brain developmental disorders
Identifying a causal genetic mutation in a person requires functional studies to determine if the mutation causes a change in the function of the gene. This work requires in-depth analysis in animal models to examine gene function in cellular proliferation, differentiation, migration and cortical wiring. We are interested to understand the basic mechanisms regulating these developmental events and hwo they are altered in human brain disorders including agenesis of the corpus callosum, ventriculomegaly, hydrocephalus and cortical malformations. This work has a significant translational impact on understanding the causes of brain developmental disorders.
Opportunities exist for students with a background or interest in: Neuroscience, genetics, cell biology, developmental biology, glial development, animal behaviour, medicine.
The function of early neuronal activity on the formation of neocortical circuits
How does the brain acquire its connectivity pattern during development? This project aims at elucidating the main roles of early sensory and spontaneous activity in the formation of neocortical circuits. By combining molecular, electrical and developmental manipulations in developing mammalian embryos and pups, this project will study how early events affect the precise formation of cortical features required for normal cognitive development. The work will have a significant impact on our understanding of how the brain is wired for function.
Opportunities exist for students with a background or interest in: Neuroscience, developmental neurobiology, neurophysiology, electrophysiological signal analysis and/or computational sciences, mathematical modelling, medicine.
Principles of neural development applied to understanding brain cancer
Brain cancer is a significant health problem in Australia. One of the most aggressive forms of brain cancer is glioblastoma (GBM) and the prognosis for these patients is extremely poor. What is needed is a deeper understanding of the cause of brain cancer. We are approaching this challenge by utilising the principles of neural development to understand how tumours first arise in the brain and how they are able to continue to grow and metastasize in order to find the causes and treatments for adult and pediatric brain cancers that originate from glia. Nuclear factor one (NFI) genes have been implicated in brain cancer and in glial development. We have generated a number of animal models of Nfi gene mis-expression to determine the function of NFI genes in brain cancer. This work will have a significant impact on our understanding of the cause and progression of brain cancer.
Opportunities exist for students with a background or interest in: Neuroscience, genetics, cell biology, developmental biology, glial development, animal behaviour, medicine.
Group Leader Associate Professor Massimo Hilliard m.hilliard@uq.edu.au
Identifing genes and conditions that control axonal regeneration
How neurons can maintain their axonal structure and function over time is not well understood. Axonal degeneration is a critical and common feature of many peripheral neuropathies, neurodegenerative diseases and nerve injuries. The genetic factors and the cellular mechanisms that prevent axonal degeneration under normal conditions and that trigger it under pathological ones are still largely unknown. We aim to use C. elegans genetics to identify the molecules and the mechanisms that control these processes.
Identifing molecules and mechanisms of axonal degeneration
How some axons can regenerate after nerve damage while others cannot is a crucial question in neurobiology, and the answers will be of great value for the medical handling of neurodegenerative diseases and of traumatic nerve injuries. Largely unknown are the molecules and the mechanisms underlying this important biological process. In C. elegans, a new laser-based technology allows single neuron axotomy in living animals, and axonal regeneration can now be visualised in real-time and tackled with a genetic approach. Our goal is to identify the genes and conditions that control this fascinating process.
Group Leader Associate Professor Helen Cooper h.cooper@uq.edu.au
Investigating the mutations in genes that impact corical development
The intricate neural architecture of the 6-layered mammalian neocortex is dependent on the ability of neural stem cells to differentiate into new neurons. These young neurons must then migrate into the correct cortical layers. In humans, mutations in genes controlling these processes have severe consequences for cortical development leading to intractable epilepsy, mental retardation, schizophrenia, dyslexia and autism.
Identifing molecular targets for axon regrowth
The corpus callosum is the major axon tract connecting the left and right hemispheres in the human neocortex. There are more than 50 different human congenital syndromes, often associated with mental retardation and epilepsy, in which this axon tract fails to develop. This project aims to identify molecular targets that can be manipulated to encourage axon regrowth and correct pathfinding in the damaged human brain and spinal chord.
Group Leader Professor Geoffrey Goodhill g.goodhill@uq.edu.au
Investigating the rules developing axons use to respond to both single and multiple molecular guidance cues
We are developing new microfluidic gradient technologies to investigate the rules developing axons use to respond to both single and multiple molecular guidance cues. This project is suitable for students with a strong biology or bioengineering background. Experience in tissue culture would be advantageous. For more details about the lab see cns.qbi.uq.edu.au.
Group Leader Professor Linda Richards richards@uq.edu.au
Human agenesis of the corpus callosum, autism spectrum disorder and brain wiring
Agenesis of the corpus callosum is a brain wiring alteration that occurs during brain development. Many people have some characteristics that are similar to those with autism spectrum disorder. We are investigating brain wiring connectivity using high-field magnetic resonance imaging and neuropsychological testing to understand how brain connectivity underpins the function of the brain. We also want to understand the underlying causes of agenesis of the corpus callosum by performing genetic analyses of DNA from people with these disorders compared to controls. The work will have a significant impact on our understanding of how changes in brain wiring impact brain function.
Opportunities exist for students with a background or interest in: Neuroscience, genetics, magnetic resonance imaging and physics, neuropsychology, medicine, computer science (data analysis and software development).
Function of genes and molecules in agenesis of the corpus callosum and brain developmental disorders
Identifying a causal genetic mutation in a person requires functional studies to determine if the mutation causes a change in the function of the gene. This work requires in-depth analysis in animal models to examine gene function in cellular proliferation, differentiation, migration and cortical wiring. We are interested to understand the basic mechanisms regulating these developmental events and hwo they are altered in human brain disorders including agenesis of the corpus callosum, ventriculomegaly, hydrocephalus and cortical malformations. This work has a significant translational impact on understanding the causes of brain developmental disorders.
Opportunities exist for students with a background or interest in: Neuroscience, genetics, cell biology, developmental biology, glial development, animal behaviour, medicine.
The function of early neuronal activity on the formation of neocortical circuits
How does the brain acquire its connectivity pattern during development? This project aims at elucidating the main roles of early sensory and spontaneous activity in the formation of neocortical circuits. By combining molecular, electrical and developmental manipulations in developing mammalian embryos and pups, this project will study how early events affect the precise formation of cortical features required for normal cognitive development. The work will have a significant impact on our understanding of how the brain is wired for function.
Opportunities exist for students with a background or interest in: Neuroscience, developmental neurobiology, neurophysiology, electrophysiological signal analysis and/or computational sciences, mathematical modelling, medicine.
Principles of neural development applied to understanding brain cancer
Brain cancer is a significant health problem in Australia. One of the most aggressive forms of brain cancer is glioblastoma (GBM) and the prognosis for these patients is extremely poor. What is needed is a deeper understanding of the cause of brain cancer. We are approaching this challenge by utilising the principles of neural development to understand how tumours first arise in the brain and how they are able to continue to grow and metastasize in order to find the causes and treatments for adult and pediatric brain cancers that originate from glia. Nuclear factor one (NFI) genes have been implicated in brain cancer and in glial development. We have generated a number of animal models of Nfi gene mis-expression to determine the function of NFI genes in brain cancer. This work will have a significant impact on our understanding of the cause and progression of brain cancer.
Opportunities exist for students with a background or interest in: Neuroscience, genetics, cell biology, developmental biology, glial development, animal behaviour, medicine.
Group Leader Associate Professor Massimo Hilliard m.hilliard@uq.edu.au
Identifing genes and conditions that control axonal regeneration
How neurons can maintain their axonal structure and function over time is not well understood. Axonal degeneration is a critical and common feature of many peripheral neuropathies, neurodegenerative diseases and nerve injuries. The genetic factors and the cellular mechanisms that prevent axonal degeneration under normal conditions and that trigger it under pathological ones are still largely unknown. We aim to use C. elegans genetics to identify the molecules and the mechanisms that control these processes.
Identifing molecules and mechanisms of axonal degeneration
How some axons can regenerate after nerve damage while others cannot is a crucial question in neurobiology, and the answers will be of great value for the medical handling of neurodegenerative diseases and of traumatic nerve injuries. Largely unknown are the molecules and the mechanisms underlying this important biological process. In C. elegans, a new laser-based technology allows single neuron axotomy in living animals, and axonal regeneration can now be visualised in real-time and tackled with a genetic approach. Our goal is to identify the genes and conditions that control this fascinating process.
Group Leader Associate Professor Helen Cooper h.cooper@uq.edu.au
Investigating the mutations in genes that impact corical 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.
Computation and Neuronal Circuits
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 brain code visual activity. Analysing this data involves advanced methods in image processing, statistical modelling and mathematical theories of neural coding. The overall aim is to determine the extent to which noise correlations play a role in conveying information about the stimulus in this context. This project 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. Analysing this data involves advanced methods in image processing and statistical modelling. The overall aim is to determine the rules which govern nerve fibre growth, particularly in chemical gradients. This project is suitable for mathematics, physics, engineering or computer science students, particularly those with a strong programming background.
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 brain code visual activity. Analysing this data involves advanced methods in image processing, statistical modelling and mathematical theories of neural coding. The overall aim is to determine the extent to which noise correlations play a role in conveying information about the stimulus in this context. This project 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. Analysing this data involves advanced methods in image processing and statistical modelling. The overall aim is to determine the rules which govern nerve fibre growth, particularly in chemical gradients. This project is suitable for mathematics, physics, engineering or computer science students, particularly those with a strong programming background.
Ageing and Dementia Research
Group Leader Professor Jürgen Götz (CJCADR) j.goetz@uq.edu.au
The function of the three murine and six human tau isoforms
The laboratory has an increasing interest in understanding the function of the three murine and six human tau isoforms. This is not a pure academic exercise as in frontotemporal dementia a slight change in isoform composition over time is sufficient to cause neurodegeneration and dementia. The project will involve developing tools such as monoclonal antibodies and using confocal microscopy and mass spectrometry to determine the specific role of the tau isoforms. A further project is in understanding site-specific phosphorylation under physiological conditions as 20% of tau’s amino acids can be potentially phosphorylated. Basic expertise in tissue culture and biochemical techniques is required, while experience in proteomics, mass spectrometry, Western blotting and immunochemical and histological techniques would be advantageous.
TH-positive neuron and protein mapping
The K369I tau-expressing K3 mouse strain is characterized by a progressive loss of TH (tyrosine hydroxylase)-positive neurons in the substantia nigra. By two years of age, 60% of the TH-positive neurons are gone. What protects some neurons while others degenerate others is not understood. The project will involve Affymetrix screening in mice followed by a rescue in the roundworm C. elegans followed by a therapy in the K3 mice using viral (AAV) methods. It will further involve the mapping of protein/protein interactions to develop a potential therapy. Basic expertise in cell culture and molecular biology techniques is required, while experience in transcriptomics, biochemistry techniques including western blotting, and animal experimentation would be advantageous.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr J Bertran-Gonzalez j.bertrangonzalez@uq.edu.au
Correlations of cellular alterations with motivational deficits
Motivated behaviours involve a myriad of goal-directed actions that are fundamental for human adaptation and survival. Diminished motivation, or apathy, is particularly common in the healthy elderly population and is an important risk factor for the development of dementia. A brain region that is central for motivated behaviours is the striatum, as it integrates multiple neurotransmitter signals to mediate learning and performance of goal-directed actions. In the present project, we seek to study the possible cellular alterations present in the different neuronal populations of the striatum, and to correlate such alterations with specific motivational deficits displayed by aged individuals.
Goal-directed learning
Goal-directed behaviours are fundamental for adaptation and survival, and comprise all actions oriented towards the fulfilment of everyday needs. Learning processes allow initial goal-directed actions to progressively arrange into organised sequences that maximise the achievement of such needs. Taking advantage of well-established behavioural paradigms, modern microscopy and transgenic technologies, we aim to determine the specific brain circuits involved in the initial acquisition and subsequent refinement of action sequences throughout goal-directed learning. Elucidation of these processes is crucial to understand how individuals can interact with and efficiently adapt to competitive changing environments.
Basal ganglia function
Classic theories of basal ganglia function argue that direct and indirect pathway circuits exert opposing regulation upon action: the direct pathway is thought to mediate actions by promoting movement, whereas the indirect pathway would refine these actions by inhibiting exceeding movements. In the recent years this vision has been challenged, and a broader view of direct/indirect regulations of basal ganglia function has been proposed. In this project we seek to understand how these two basal ganglia circuits are reconciled during the execution of action by determining whether direct and indirect pathway populations antagonise each other—or rather cooperate—to produce actions.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Liviu Bodea l.bodea@uq.edu.au
Understanding of TYROBP and TREM2 and what microglia contribute to AD pathogenesis
Systemic inflammatory reactions have been postulated to exacerbate neurodegenerative diseases via microglial activation. To characterize molecular systems associated with Alzheimer's disease (AD), a gene-regulatory networks had been constructed in 1,647 postmortem brain tissues from AD patients and nondemented controls, demonstrating that AD reconfigures specific portions of the molecular interaction structure. Through an integrative network-based approach, these network structures were rank-ordered for relevance to AD pathology, highlighting an immune- and microglia-specific module that is dominated by genes involved in pathogen phagocytosis. We identified a key microglial molecule, TYROBP (also known as DAP12) that is upregulated in AD. TYROBP forms a complex with TREM2, that is encoded by a gene that has recently been identified as an AD risk gene. This project is about gaining a deeper understanding of both TYROBP and TREM2 and what microglia contribute to AD pathogenesis.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Rebecca Nisbet r.nisbet@uq.edu.au
Understanging amyloid-beta microglial receptors and clearance
The accumulation of amyloid-beta in AD brain is a consequence of both an increased production and an impaired clearance. Our laboratory aims to better understand how clearance of amyloid-beta is impaired in AD and in developing strategies to assist in amyloid clearace. Here, microglial cells have been shown to have a key role. This project is about determining which microglial receptors have a role in amyloid-beta uptake, understanding how amyloid-beta is cleared by microglia, and finally, developing strategies to facilitate an increased uptake of amyloid-beta and subsequent clearance. The project will involve cloning (Gateway vector), cell culture, histology and biochemical analysis.
Improving motor or memory function with active and passive immunisation
Ongoing clinical trials in Alzheimer's disease employ both active and passive immunization approaches targeting the toxic peptide amyloid-beta. We have shown recently, that the intracellular protein tau is also a suitable target for therapeutic intervention, using FTD tau transgenic mouse models. By active and passive immunisation of FTD mutant tau transgenic mouse models we have shown that this results in an improvement using biochemical and histological read-outs. However, we failed to achieve an improvement in motor or memory functions. To achieve this goal we are currently developing single chain antibodies. Moreover, because tau is aggregating intracellularly, we are developing these antibodies further to use them as intrabodies. For delivery we will use both viral vectors and focused ultrasound.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr J Chuanzhou Joe Li j.bertrangonzalez@uq.edu.au
Assessing the structural changes in the spine
The protein tau and the peptide Abeta form the two key lesions in the Alzheimer brain, the neurofibrillary tangles and the amyloid plaques. Tau is essential for Abeta to mediate its toxic effects including excitotoxic signaling. This project will assess the structural changes in the spine that make mice in which the interaction of NMDAR and PSD95 has been transiently disrupted permanently resistant to Abeta toxicity. The project will further address the role of these interactions in learning and memory using transgenesis and complementary mouse and C. elegans models. - Basic expertise in biochemistry and molecular biology techniques is required, while some experience in animal experimentation (including behaviour), biochemistry techniques including western blotting, and histology would be advantageous.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Juan Carlos Polanco j.polanco@uq.edu.au
Are nanovesicles isolated from AD transgenic toxic and do they elicit an AD pathomechanism in recipient cells
Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid and TAU. The AD pathology usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas. AD progression is characterized by increasing TAU aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via nanovesicles such as exosomes or microvesicles. Using AD mouse models with Tau overexpression, we found that Tau transgenic mice have indeed nanovesicles that contain TAU protein. This project is about the characterization of these nanovesicles and the question whether nanovesicles isolated from AD transgenic are toxic and elicit an AD pathomechanism in recipient cells.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Robert Hatch j.goetz@uq.edu.au
Using electrophysiology to understand effects on signaling properties of neurons
This project is about the application of electrophysiology (field recordings and paired recordings from up to four cells) to determine how pathological changes such as tau hyperphosphorylation, tau aggregation and exposure to oligomeric Abeta affect the signaling properties of neurons in slices or as dispersed cultures. To address this fundamental question we use both transgenic mouse models as well as human and murine cell lines that are being microinjected with tau aggregates.
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 Professor Jürgen Götz (CJCADR) j.goetz@uq.edu.au
The function of the three murine and six human tau isoforms
The laboratory has an increasing interest in understanding the function of the three murine and six human tau isoforms. This is not a pure academic exercise as in frontotemporal dementia a slight change in isoform composition over time is sufficient to cause neurodegeneration and dementia. The project will involve developing tools such as monoclonal antibodies and using confocal microscopy and mass spectrometry to determine the specific role of the tau isoforms. A further project is in understanding site-specific phosphorylation under physiological conditions as 20% of tau’s amino acids can be potentially phosphorylated. Basic expertise in tissue culture and biochemical techniques is required, while experience in proteomics, mass spectrometry, Western blotting and immunochemical and histological techniques would be advantageous.
TH-positive neuron and protein mapping
The K369I tau-expressing K3 mouse strain is characterized by a progressive loss of TH (tyrosine hydroxylase)-positive neurons in the substantia nigra. By two years of age, 60% of the TH-positive neurons are gone. What protects some neurons while others degenerate others is not understood. The project will involve Affymetrix screening in mice followed by a rescue in the roundworm C. elegans followed by a therapy in the K3 mice using viral (AAV) methods. It will further involve the mapping of protein/protein interactions to develop a potential therapy. Basic expertise in cell culture and molecular biology techniques is required, while experience in transcriptomics, biochemistry techniques including western blotting, and animal experimentation would be advantageous.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr J Bertran-Gonzalez j.bertrangonzalez@uq.edu.au
Correlations of cellular alterations with motivational deficits
Motivated behaviours involve a myriad of goal-directed actions that are fundamental for human adaptation and survival. Diminished motivation, or apathy, is particularly common in the healthy elderly population and is an important risk factor for the development of dementia. A brain region that is central for motivated behaviours is the striatum, as it integrates multiple neurotransmitter signals to mediate learning and performance of goal-directed actions. In the present project, we seek to study the possible cellular alterations present in the different neuronal populations of the striatum, and to correlate such alterations with specific motivational deficits displayed by aged individuals.
Goal-directed learning
Goal-directed behaviours are fundamental for adaptation and survival, and comprise all actions oriented towards the fulfilment of everyday needs. Learning processes allow initial goal-directed actions to progressively arrange into organised sequences that maximise the achievement of such needs. Taking advantage of well-established behavioural paradigms, modern microscopy and transgenic technologies, we aim to determine the specific brain circuits involved in the initial acquisition and subsequent refinement of action sequences throughout goal-directed learning. Elucidation of these processes is crucial to understand how individuals can interact with and efficiently adapt to competitive changing environments.
Basal ganglia function
Classic theories of basal ganglia function argue that direct and indirect pathway circuits exert opposing regulation upon action: the direct pathway is thought to mediate actions by promoting movement, whereas the indirect pathway would refine these actions by inhibiting exceeding movements. In the recent years this vision has been challenged, and a broader view of direct/indirect regulations of basal ganglia function has been proposed. In this project we seek to understand how these two basal ganglia circuits are reconciled during the execution of action by determining whether direct and indirect pathway populations antagonise each other—or rather cooperate—to produce actions.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Liviu Bodea l.bodea@uq.edu.au
Understanding of TYROBP and TREM2 and what microglia contribute to AD pathogenesis
Systemic inflammatory reactions have been postulated to exacerbate neurodegenerative diseases via microglial activation. To characterize molecular systems associated with Alzheimer's disease (AD), a gene-regulatory networks had been constructed in 1,647 postmortem brain tissues from AD patients and nondemented controls, demonstrating that AD reconfigures specific portions of the molecular interaction structure. Through an integrative network-based approach, these network structures were rank-ordered for relevance to AD pathology, highlighting an immune- and microglia-specific module that is dominated by genes involved in pathogen phagocytosis. We identified a key microglial molecule, TYROBP (also known as DAP12) that is upregulated in AD. TYROBP forms a complex with TREM2, that is encoded by a gene that has recently been identified as an AD risk gene. This project is about gaining a deeper understanding of both TYROBP and TREM2 and what microglia contribute to AD pathogenesis.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Rebecca Nisbet r.nisbet@uq.edu.au
Understanging amyloid-beta microglial receptors and clearance
The accumulation of amyloid-beta in AD brain is a consequence of both an increased production and an impaired clearance. Our laboratory aims to better understand how clearance of amyloid-beta is impaired in AD and in developing strategies to assist in amyloid clearace. Here, microglial cells have been shown to have a key role. This project is about determining which microglial receptors have a role in amyloid-beta uptake, understanding how amyloid-beta is cleared by microglia, and finally, developing strategies to facilitate an increased uptake of amyloid-beta and subsequent clearance. The project will involve cloning (Gateway vector), cell culture, histology and biochemical analysis.
Improving motor or memory function with active and passive immunisation
Ongoing clinical trials in Alzheimer's disease employ both active and passive immunization approaches targeting the toxic peptide amyloid-beta. We have shown recently, that the intracellular protein tau is also a suitable target for therapeutic intervention, using FTD tau transgenic mouse models. By active and passive immunisation of FTD mutant tau transgenic mouse models we have shown that this results in an improvement using biochemical and histological read-outs. However, we failed to achieve an improvement in motor or memory functions. To achieve this goal we are currently developing single chain antibodies. Moreover, because tau is aggregating intracellularly, we are developing these antibodies further to use them as intrabodies. For delivery we will use both viral vectors and focused ultrasound.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr J Chuanzhou Joe Li j.bertrangonzalez@uq.edu.au
Assessing the structural changes in the spine
The protein tau and the peptide Abeta form the two key lesions in the Alzheimer brain, the neurofibrillary tangles and the amyloid plaques. Tau is essential for Abeta to mediate its toxic effects including excitotoxic signaling. This project will assess the structural changes in the spine that make mice in which the interaction of NMDAR and PSD95 has been transiently disrupted permanently resistant to Abeta toxicity. The project will further address the role of these interactions in learning and memory using transgenesis and complementary mouse and C. elegans models. - Basic expertise in biochemistry and molecular biology techniques is required, while some experience in animal experimentation (including behaviour), biochemistry techniques including western blotting, and histology would be advantageous.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Juan Carlos Polanco j.polanco@uq.edu.au
Are nanovesicles isolated from AD transgenic toxic and do they elicit an AD pathomechanism in recipient cells
Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid and TAU. The AD pathology usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas. AD progression is characterized by increasing TAU aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via nanovesicles such as exosomes or microvesicles. Using AD mouse models with Tau overexpression, we found that Tau transgenic mice have indeed nanovesicles that contain TAU protein. This project is about the characterization of these nanovesicles and the question whether nanovesicles isolated from AD transgenic are toxic and elicit an AD pathomechanism in recipient cells.
Clem Jones Centre for Ageing Dementia Research (CJCADR) under the group leadership of Professor Jürgen Götz
Dr Robert Hatch j.goetz@uq.edu.au
Using electrophysiology to understand effects on signaling properties of neurons
This project is about the application of electrophysiology (field recordings and paired recordings from up to four cells) to determine how pathological changes such as tau hyperphosphorylation, tau aggregation and exposure to oligomeric Abeta affect the signaling properties of neurons in slices or as dispersed cultures. To address this fundamental question we use both transgenic mouse models as well as human and murine cell lines that are being microinjected with tau aggregates.
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.