Research Opportunities

The use of electric medicine devices to stimulate the autonomic nervous system has given rise to a broad range of promising new treatments for autoimmune diseases and chronic conditions and has gained significant momentum in the medical research community. However, most devices used to deliver bioelectric therapy are open-loop and provide a fixed level of stimulation that does not respond to individual needs.

The next generation of bioelectric neuromodulation devices aim to provide closed loop (adaptive) control, in which the level of stimulation adjusts to a patient’s rapidly changing needs.

The Peripheral Interface Neuromodulation Team at the Bionics Institute are developing a range of vagus nerve devices to prevent the recurrence of Crohn’s disease; and are developing similar devices to reduce inflammation in rheumatoid arthritis, in addition to a peripheral nerve device to improve bladder control. This approach offers exciting possibilities for the future treatment of autoimmune diseases and chronic conditions.

Cats in Australia were believed to have originated with the British colonisation, hence are foreign animals to the continent and have spread over 99% of it. Cats are important pets in Australian households, and as of 2019, approximately 27% of households hosted at least one cat, with nearly 3.9 million cats kept as companion animals. However, they are widely known to prey on native Australian fauna, which has led to the extinction of 25 species and threatens 100 more species. Furthermore, pathogens that require feline hosts for their life cycles cause approximately AU$6 billion in losses to the economy by infecting livestock and humans every year.

Given the important ecological, economic, public health, and companionship roles of domestic cats, as well as the role of feral cats as pests, this research will explore the parasite diversity of felines and the impact of feral cats on native wildlife across Australia using a combination of post mortem, classical and advanced molecular diagnostic techniques.

We are interested in how genes and environment combine to sculpt brain development and function, in health and disease. We have examined the role of various molecular and cellular mediators, and environmental modulators, as they influence healthy cognitive and affective function on the one hand, and cognitive and affective disorders on the other. These findings have been extended to include environmental manipulations in models of various brain disorders, including autism, schizophrenia, depression, and anxiety disorders.

We have also discovered altered brain-body interactions, including the first evidence of gut dysbiosis (dysregulated microbiota) in Huntington’s disease, and a preclinical model of schizophrenia. Ongoing studies are exploring the gut microbiome as a therapeutic target and the possibility that specific environmental factors may modulate brain function via microbiota-gut-brain interactions.

In a parallel program of research, we have been exploring epigenetic inheritance via the paternal lineage. We have discovered the transgenerational effects of various paternal environmental exposures. Our findings reveal significant experience-dependent effects on cognitive and affective function of offspring via epigenetic inheritance. We are investigating the relevance of these discoveries in mice to human transgenerational epigenetics and associated ‘epigenopathy’. Our ongoing studies are exploring mechanisms whereby experience can modify germ cells and associated sperm epigenetics, and how these epigenetic modifications (of mice and men) may modulate offspring phenotypes and their potential susceptibility to various brain disorders.

Our research links data at behavioural and cognitive levels to underlying cellular and molecular mechanisms. We use a variety of behavioural tools, including automated touchscreen testing of cognition, that are directly translatable to clinical tests. We are establishing the extent to which experience-dependent plasticity can modulate these behavioural and cognitive endophenotypes, in models with targeted genome editing. This cellular level of understanding is linked, in turn, to molecular mechanisms, including epigenetics, transcriptomics and proteomics.

Based on this research, and the identification of key target molecules, we are also exploring the concept of ‘enviromimetics’, therapeutics that mimic or enhance the beneficial effects of cognitive stimulation and physical exercise. One goal is to develop such therapeutic agents to help reduce the personal and societal burdens of these devastating brain disorders.

Genetic Diagnosis of Children with Vascular Anomalies for a Therapeutic Clinical Drug Trial.

Our understanding of the genetics of vascular anomalies is rapidly advancing but remains incompletely understood. An inherited germline mutation may lead to a predisposition to developing vascular anomalies, with a ‘second hit’ somatic mutation occurring within the affected tissues. In other sporadic cases a somatic variant alone arising in the affected tissue at low frequency during early development may be sufficient to cause the vascular anomaly. The Vascular Anomaly Clinic at RCH has a large cohort of patients with a wide variety of vascular anomalies, including those associated with overgrowth syndromes. Most of these patients are sequencing naïve and are being tested for a genetic diagnosis in the Translational Neurogenetics Laboratory at Austin Health.

Analysis of DNA from blood may not identify a mutation in individuals with vascular anomalies, however sequencing tissue extracted from surgical specimens may identify the causative variant. Technologies such as high-depth sequencing or droplet digital PCR are key in detecting and quantifying mosaic variants in various tissues. Patients in whom appropriate variants are identified will be eligible for enrolment in our new 5-year MRFF-funded Rare Cancers Rare Diseases Unmet Needs (RCRDUN) Clinical Trial of targeted therapies for vascular anomalies commencing in 2023.

Aims:

1. To perform high depth gene panel or exome sequencing, or sensitive droplet digital PCR, to detect germline or somatic variants in individuals from large families with multiple affected individuals, sporadic cases, or those with atypical clinical presentations, to identify causative mutations in known and novel genes.
2. To gain hands-on experience with current genomic technologies and understand appropriate application, strengths, and limitations of these technologies.
3. To understand the pathway from the clinic, through the laboratory process, to molecular diagnosis and back to the bedside, culminating in clinical trial of targeted drug therapies for patients with severe disease intractable to standard care.

Methodology:

1. Recruitment of families with multiple affected individuals and sporadic cases without family history.
2. Application of current genomic testing technologies to these families and individuals using paired DNA samples extracted from lymphocytes and from surgical tissue to identify causative mutations.
3. This project provides the opportunity to work in an established multidisciplinary clinical and laboratory research team with clinical trial expertise. In addition to clinical experience and laboratory techniques, the development of project management, sample coordination and communication skills will be fostered.

Our research group conducts multidisciplinary research to study enzymes with a focus on structure, function, and modulation. We apply a range of biophysical, chemical biology and structural biology techniques to enable our discoveries.

Our research aims to elucidate and understand how enzyme activities are regulated so that we can gain insights into their biological functions. Specifically, we study how (i) posttranslational modifications, (ii) metabolites, and (iii) synthetic inhibitors modulate to the structure and activity of enzymes. We apply the knowledge to understand how intracellular bacteria such as Mycobacterium tuberculosis adjust their metabolism to survive in nutrient-deprived environments, and how plants response to abiotic stress.

We aim to harness the catalytic activity of enzymes to break down environmental pollutants. Specifically, we study how oxidative enzymes such as laccase may be applied to degrade emerging contaminants.

Available summer project:

A key step of our work involves the production and purification of recombinant proteins. In this summer project, you will conduct experiments to genetically modify microorganisms to produce recombinant proteins as well as optimising the procedure for protein purification. If time permits, you will also have the opportunity to use biophysical tools (such as mass spectrometry) to characterise the proteins that you will make.

An understanding of basic molecular biology and an enthusiasm in enzymology will be helpful. Training and supervision will be provided throughout the summer period. You will be an integral part of our research group and contribute to the generation of new knowledge for scientific publications.

Examples of recent work from our group that include contribution from summer students:

– Correddu, D.; Montaño López, J. d. J.; Angermayr, S. A.; Middleditch, M. J.; Payne, L. S.; Leung, I. K. H. Effect of Consecutive Rare Codons on the Recombinant Production of Human Proteins in Escherichia coli. IUBMB Life 2020, 72, 266–274.

– Correddu, D.; Montaño López, J. d. J.; Vadakkedath, P. G.; Lai, A.; Pernes, J. I.; Watson, P. R.; Leung, I. K. H. An Improved Method for the Heterologous Production of Soluble Human Ribosomal Proteins in Escherichia coli. Sci. Rep. 2019, 9, 8884.

Please feel free to contact me by email if you would like to find out more about our research!

Our brains are constantly adapting to the world around us. For people with hearing loss, their brains can change due to the loss of hearing and subsequent restoration of hearing via medical devices. Cochlear implants are auditory prostheses, pioneered at the Bionics Institute and the University of Melbourne, which restore the sense of hearing to the severe-to-profoundly deaf.

In the Translational Hearing Research Team at the Bionics Institute of Australia, we are pioneering the use of functional near-infrared spectroscopy (fNIRS) to study changes in the hearing-impaired brain within the year after cochlear implantation. Join our multi-disciplinary team of engineers, clinicians, and scientists as we uncover the different conditions in the brain which limit how well people can do with their cochlear implants. These observations will help implant recipients better understand the challenges they will face on their hearing journey and guide clinicians towards better rehabilitation strategies for cochlear implant recipients. Ultimately, our research will improve speech understanding outcomes for cochlear implant users, allowing them to hear more confidently while studying, working, or relaxing.

As a part of our team, you will have the opportunity to observe clinical hearing research, learn about functional brain imaging, and perform state-of-the-art analysis of imaging data. Our research project will help you develop a keen sense of statistics, which will become useful during your future research career.

The function of the largest area of our brain, the cortex, is one of the great mysteries of neuroscience. Despite decades of research, the role of the cortex is largely unrealised, and we are just starting to appreciate its contribution to many important brain functions, such as learning and memory.

Our goal is to understand how cortical neurons, and their dendrites, encode information and how this process is modulated throughout learning and memory. We use advanced imaging and electrophysiology approaches to tackle these questions, including patch clamp electrophysiology, two-photon calcium imaging, widefield imaging, and optogenetics in vitro and in vivo. By investigating single neurons and neural networks that drive behaviour, we aim to highlight changes that occur within these networks during brain function and dysfunction, with a particular focus on brain cancer.

As an Amgen scholar, you would be involved in the research that is conducted with the laboratory and will learn how to analyse imaging and electrophysiological data.

The growing preference for functional foods favours the probiotic and prebiotic market growth and is expected to reach over USD 66 billion by 2024. Probiotics are live microorganisms which when administered in adequate amounts confer health benefits on the host through enhancing gut microbiome. Probiotics are associated with maintaining optimum microbial balance in the digestive tract with a number of well-documented health benefits. Therefore, these organisms such as lactobacilli and bifidobacteria have been extensively incorporated into various food products over the last decade.

Colonic foods, which encourage the growth of favourable bacteria, are referred to as prebiotics. There is an obvious potential for a synergetic effect when combining probiotics and prebiotics appropriately because prebiotics promote the growth and activities of probiotics. Traditionally, probiotic delivery has been associated with dairy foods, however there is an increasing demand for non-dairy probiotic products due to vegetarianism, concerns over milk cholesterol content, and lactose intolerance. In order to provide beneficial health effects for the host animal, probiotic bacteria must survive through the gastrointestinal tract, tolerating acid, bile, and gastric enzymes, and then adhere and colonize in the intestinal epithelium. These functional properties can be influenced by the type of food carriers used in probiotic delivery. Hence, studies evaluating the influence of various food substrates such as plant-based food matrices on probiotic functional efficacy are crucial.

Our recent work focus on the impact of various food substrates on the gastrointestinal tolerance of selected probiotics strains, their colonic fermentation in vitro and metabolites produced in the gut environment. In addition, we use cell culture techniques with respect to probiotic adhesin into intestinal epithelium and basic molecular biological applications.

An exciting opportunity has arisen in the Medical Accelerator Physics group at the University of Melbourne. Based in the School of Physics, the student will join the research team of the new X-Band Laboratory for Accelerators and Beams (X-LAB), developed in collaboration with CERN (home of the Large Hadron Collider).

The X-LAB is the first X-band accelerator test facility in the southern hemisphere. The term “X-band” refers to the ultra-high-frequency at which the device operates: this high frequency means the accelerators are physically smaller and lighter than existing technology.

Our current focus entails collaborating with CERN to investigate potential acceleration systems for the compact linear collider (CLIC), as detailed on the following website: https://home.cern/science/accelerators/compact-linear-collider

Our specific experiment involves configuring a test stand for characterising high gradient accelerating structures. The objective is to assess the feasibility of developing structures capable of operating with accelerating gradients on the order of 100 MV/m. To generate these gradients, accelerating structures undergo conditioning with 12 GHz RF. The RF is pulsed at 400 Hz with pulse lengths of 250 ns, and with flat top power ranges spanning from 0 to 50 MW.

The X-LAB student will be involved in daily laboratory activities, specifically testing components and equipment.

Designing Emulsion Nanoparticles for Targeting Biofilms.

Bacterial infections are a critical issue for modern healthcare. Many bacterial infections involve the formation of biofilms which provides bacteria with additional protection and thus extra resistance to treatment. pH responsive nanoparticles are attractive for the targeted delivery of active agents to a biofilm due the lower pH of this environment. Antimicrobial peptides (AMPS) are an interesting class of active agent to kill bacteria as they typically have a broad mode of action which limits the ability of bacteria to become resistant.

In this project we aim to design pH responsive emulsion nanoparticles that can encapsulate antimicrobial peptides and antibiotics and release them based on a decrease in pH, thus mimicking the biofilm environment. The project will investigate if can achieve synergistic killing by combination in the one nanoparticle. The project will involve nanoparticle synthesis and optimisation as well as bacterial assays to optimise activity.

A project on radiopharmaceutical synthesis will be carried out in collaboration with the Austin Hospitac PET imaging centre and the Olivia Newton John Cancer Research Institute. The student will synthesise a precursor drug molecule in preparation for 18-F radiolabellinng at the Austin Hospital

Inorganic chemistry and metal based drugs.

Total synthesis of natural products. Synthesis of novel metal complexes for catalysis. Medicinal chemistry

G protein-coupled receptors (GPCRs) are the most important cellular sensors in the human body and drugs targeting GPCRs account for ~40% of all prescription drugs. Conversely, over 85% (>310 receptors) of the GPCR family is not currently targeted by drugs. In particular neuropeptide GPCRs, although linked to the pathogenesis of many diseases, have proved to be especially difficult to target with drugs. The reason for this is that very little is known about the molecular mechanisms underlying GPCR binding and activation, thus hampering drug development.

Our laboratory targets GPCRs for drug development utilizing state-of-the-art molecular pharmacology, biochemical and Nuclear magnetic resonance (NMR) techniques. These techniques enable us to map the native ligand binding sites of these receptors and determine the mechanisms of receptor activation as well their cell signalling characteristics. A complete understanding of the mechanism of ligand binding and activation is required to design drugs targeting these receptors. Furthermore, we are utilizing novel protein engineering techniques that enable these normally highly unstable proteins to be produced and purified for structural studies using advanced protein NMR techniques, crystallography and Cryo-EM. These studies are complemented by peptide drug development projects and small molecule screening projects with collaborators. Additionally, we are working with pharmaceutical industry partners (e.g. Takeda and Novartis) to facilitate drug development efforts.