PHARMACOLOGY AND THERAPEUTICS 2021 - RESEARCH PROJECTS HONOURS, MASTERS AND PHD - School of Biomedical ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
P H A R M A CO LO G Y A N D T H E R A P E U T I CS 2021 R E S E A R C H P R OJ E C TS H O N O U R S , M A ST E R S AND PHD
WELCOME It is a great pleasure to introduce you to the research projects that are on offer by the Department of Pharmacology and Therapeutics for 2021. Most projects offered will be in our spacious, high quality research laboratories on the 8th and 9th floors of the Medical Building. The remainder will be conducted in affiliated Research Institutes with external supervisors and co-supervision by Department staff. The Department of Pharmacology and Therapeutics Honours and Masters Course is directed at students with above average academic ability. The year is a transition year from formal lectures and teaching, to self-directed learning and exploration of your own scientific problem. We will introduce you to skills in communication, data analysis and assessment of scientific papers. Your supervisor and laboratory staff will guide you through the challenges, strengthen your technical skills and introduce you to the excitement of research - its rewards and its disappointments. You will have the opportunity to use the latest in equipment and work alongside other researchers to expand biomedical knowledge. The Honours and Masters “Experience” will require self-motivation and discipline, and you will learn a lot about your own problem-solving ability. It is not a simple task to select a project, laboratory and supervisor. We suggest you talk to several potential supervisors, as well as to their current Honours, Masters Students or Graduate Researchers, to gain some appreciation of the research problems being addressed and the related techniques. You will find them friendly and welcoming! We hope you will join us in Pharmacology & Therapeutics for the 2021 Honours and Masters Year. We aim to give you the best opportunity to ‘have a go’ at solving a research problem, teach you important skills for future employment in various biomedical vocations and provide a solid basis for those who want to go further in a research career. Very best wishes for the next step in your journey! Associate Professor Christine Wright Honours & MBiomedSci Co-ordinator Department of Pharmacology and Therapeutics FMDHS, The University of Melbourne 2
HOW TO APPLY HONOURS How long is Honours? STEP 3: Project Preference Honours is a one-year course consisting Once you have submitted an online course What is Honours? of 75 points of research and 25 points application, you will receive an email Honours is a fourth-year undergraduate of coursework, that commences mid- within 3 working days with your personal course that consists of a combination of a February and finishes in November. login details to access the Honours Project research project and coursework subjects. How to apply Preference System - SONIA. Please follow The course is designed to develop the the instruction in the email to set up your student’s capacity to solve problems, to STEP 1: Contact Potential Supervisor(s) password and select your preferences for analyse data, to read and think critically, Decide which departments, institutes, projects offered within MDHS departments. and to communicate clearly. supervisors and projects you wish to apply You may select up to 4 project preferences Honours can give you a taste of what for and make contact with the relevant in Round 1 or 3 project preferences in working as a scientist would be like as supervisor. Round 2 and 3. You must only preference a career, allows you to demonstrate projects after making contact with the academic excellence in an area of special Applicants must contact potential relevant supervisor(s). You are allowed to interest to you, and provides an entry supervisors either before or soon after log into Sonia to change your preferences point for further research higher degree submitting an online application for entry any time by the closing date. study (i.e. PhD). These skills are highly to an MDHS Honours course. Department and Institute Honours project booklets More information including application sought after by employers in biological, and websites, the individual information dates and online application link: medical and industrial areas. sessions held by departments and http://mdhs-study.unimelb.edu.au/ What are the entry requirements? institutes are ways of helping you to make degrees/honours/apply-now#apply-now To be considered for entry, applicants initial contact with potential Honours must have completed a suitable supervisors. However, if you are seriously undergraduate degree (Bachelor of considering a project you should arrange Biomedicine, Bachelor of Science or to meet your potential supervisor more equivalent) with a major in a relevant formally to get a much better idea about discipline with a WAM (weighted average the project and their expectations. mark) of at least H3 (65%) or equivalent. STEP 2: Online Application Students who have completed or are due Lodge an online application to complete a Bachelor of Biomedicine at the University of Melbourne should 1. Apply online and select either the apply to complete Biomedicine Honours. Returning Applicants, Current Students Students who have completed or are due and Previous Students or First Time to complete a Bachelor of Science at the Applicants. Do not select the First University of Melbourne or an equivalent Time Applicants option if you have course at another institution should apply previously completed study or applied to complete Science Honours. to any program at The University of Melbourne. Meeting the minimum Faculty level is not a guarantee of admission and students must 2. Select ‘MDHS Specialisations’ as be accepted by a supervisor before entry requirement response in the online into the course. application form. 3. Provide original or certified transcript(s) for any study not undertaken at The University of Melbourne. You are not required to provide transcripts for study undertaken at this university. 4
MASTER OF BIOMEDICAL SCIENCE What is the Master of Biomedical Note How to apply Science? 1. Apply online and select either Current • Quotas may be applied to the The Master of Biomedical Science at the degree as a whole, or to individual Students and Previous Students or First University of Melbourne is a coursework disciplines, and preference may be Time Applicants. Do not select the First master’s degree incorporating a given to applicants with evidence of Time Applicants option if you have substantial research project. This course appropriate preparation or potential previously completed study or applied is an alternative to the Honours as a PhD to undertake research. to any program at The University of pathway. Students undertake a major • Entry is subject to the capacity Melbourne. research project and discipline-specific of a participating department to 2. Provide original or certified transcript(s) coursework subjects. In addition, a suite of provide adequate supervision in a for any study not undertaken at The professional business and communication research project appropriate to the University of Melbourne. subjects are offered to complement and interests and preparation of the enhance the research undertaken and to individual student and is subject to Selecting a Project progress students’ career opportunities. the agreement of an academic staff Once you have submitted an online course The course encourages students to think member to supervise the project. application, you will receive an email with innovatively and provides an awareness • Students entering this course are your personal login details to access the of the health and economic benefits of expected to organise an academic Master of Biomedical Science Project biomedical research. Graduates of this supervisor in the relevant academic Preference System - SONIA. Please follow course gain an understanding of the unit, and select a research project, as the instruction in the email to set up your research process, specialist knowledge part of the application process. You password and review projects offered and professional skills that are attractive will be provided with a list of current within MDHS departments. You must make to employers. projects once your application has direct contact with the supervisor and been assessed and deemed eligible. obtain permission to work on their project What are the entry requirements? The theme and scope of the research before submitting your project preference. To be considered for entry, applicants project is negotiated between the Once your project has been endorsed, you must have completed a suitable student and supervisor prior to will be allocated to this project in SONIA. undergraduate degree with a major in a commencement of the course. More information including application relevant discipline with a WAM (weighted How long is the Master of dates and online application link: average mark) of at least H3 (65%) or Biomedical Science? https://study.unimelb.edu.au/find/ equivalent. Meeting this requirement does The Masters is a two-year (full time) course courses/graduate/master-of-biomedical- not guarantee selection. consisting of 125 points of research and 75 science/how-to-apply/ points of coursework. The course can be commenced at the start of the year or at mid-year. Difference between Honours and the Master of Biomedical Science Honours Masters Duration 1 year (full time) 2 years (full time), part time available Level Undergraduate Graduate CSP (commonwealth supported places) Yes Limited available? PhD Scholarship scoring Considers marks from 3rd year of Only Master’s marks are considered Bachelor’s degree and Honours marks International Market recognition Australian Honours degree may not be Recognised as a graduate recognised overseas, as many countries do Master’s degree not have an equivalent degree. 5
RESEARCH HIGHER DEGREES What is a PhD? What are the entry requirements? Choosing a supervisor and research area A PhD (Doctor of Philosophy) is a three- To be considered for entry into a PhD, A critical element of success is choosing year supervised research degree with the applicants must have completed a research area that interests you. possibility of up to 12 months extension. A Departmental websites have information • a four-year Bachelor's degree candidate may be required to supplement on the range of research areas on offer, as (BSc Hons, BBiomed Hons) in a their research with enrolment in additional well as areas of interest of academic staff relevant discipline which includes subjects if considered necessary. The members who can supervise your project. a substantial research component research is written up as a thesis (80,000 – equivalent to at least 25% of one year It is very important for you to talk to 100,000 words) and examined by external full time study and achieved a supervisors as well as current or previous experts in the field. minimum WAM of 80% (university of students. It is one thing to be interested in What is a MPhil? Melbourne) or equivalent; or the project but you need to get along with A MPhil (Master of Philosophy) is similar • a Master's degree in a relevant your supervisor too. If possible, try to get to a PhD but carried out over a shorter discipline which includes a some work experience in the lab to get an period of time of 18months to 2 years. substantial research component idea about the environment. The research work is written up as a equivalent to at least 25% of one year of full time study and achieved a For future information regarding Research thesis (30,000 – 40,000 words) which Higher Degrees at the University of demonstrates your knowledge and minimum weighted average of 80% or (University of Melbourne) equivalent. Melbourne see the following links: contribution to the field of research. To be considered for entry into a MPhil, https://study.unimelb.edu.au/find/ applicants must have completed courses/graduate/doctor-of-philosophy- medicine-dentistry-and-health-sciences/ • a four-year Bachelor's degree (BSc Hons, BBiomed Hons) in a https://study.unimelb.edu.au/find/ relevant discipline which includes a courses/graduate/master-of-philosophy- substantial research component mdhs-biomedical-science/ equivalent to at least 25% of one year full time study and achieved a How to apply minimum WAM of 75% or higher; or 1. Review the list of prospective projects • a Master's degree in a relevant and supervisors in this handbook discipline which includes a or online at biomedicalsciences. substantial research component unimelb.edu.au/departments/ equivalent to at least 25% of one pharmacology#research year of full-time study and achieved 2. Identify projects of interest and contact a minimum weighted average of the project supervisor to explain your (University of Melbourne) 75% or research interests and provide your higher. curriculum vitae (CV) can academic transcripts. 3. Once confirmed a project and supervisor apply online at study. unimelb.edu.au/how-to-apply/ graduate-research 7
SCHOLARSHIPS Honours Graduate degrees Honours applicants who accept and enrol The Melbourne Scholarships Program in an Honours course will automatically is one of the most generous and be considered for available Honours comprehensive in Australia, with a Scholarships. These are awarded on wide range of scholarships available for academic merit. domestic and international students. There are many different types of Highly ranked full-time students who have scholarships available, with some enrolled in an MDHS program through varying in value, duration and eligibility. the Bachelor of Biomedicine (Degree with Most University of Melbourne graduate Honours) and the Bachelor of Science students have scholarships to aid with (Degree with Honours) and demonstrated living expenses and course fees. Some a level of financial needs will automatically scholarships also assist with relocation be considered for an Frances Elizabeth fees and insurance costs whilst studying at Thomson Trust Scholarship. The the University of Melbourne. Scholarship will award eligible students with a one- off payment of $5,000. mdhs. Graduate Research Scholarships for unimelb.edu.au/study/ scholarships/n/ domestic and international students frances-elizabeth-thomson are awarded on a competitive basis. If successful, students must also meet The Dept. of Pharmacology and the entry requirements for a Doctoral Therapeutics offers financial support degree at the University of Melbourne. for Honours/Masters students to attend More details on the different types and present their research at a scientific of scholarships available, what they conference commonly, The Australasian cover and eligibility can be found here: Society of Clinical and Experimental scholarships.unimelb.edu.au/awards/ Pharmacologists and Toxicologists graduate-research-scholarships (ASCEPT). 8
ANDERSON GROUP Contact: Dr. Andrew Jarnicki Therapeutics and translation Immunopharmacology Email: andrew.jarnicki@unimelb.edu.au Location: Department of Molecular mechanisms Cellular Imaging and Pharmacology and Therapeutics of disease Structural Biology Lung Health Our research is focused on understanding the molecular basis of chronic degenerative lung diseases, in particular severe refractory asthma, Chronic Obstructive Lung Disease (COPD), Asthma-COPD Overlap, the COPD-lung cancer interface and fibrotic lung diseases. We are interested in understanding the reasons why lung disease becomes chronic and resists the normal processes that help resolve tissue damage, as well as why the damaged lung is so susceptible to subsequent infections. Our research also focuses on developing and testing experimental medicines in preclinical models. We work with leading clinicians/researchers at the RMH and internationally to translate our basic findings into useful medicines. Project: Understanding the role of the Project: Using machine learning to Project supervisor microbiome in lung viral infections improve the characterisation and Dr. Robert O’Donoghue This project addresses a major but much quantification of fibrotic lung. Project co-supervisors under-appreciated problem- vaccinations Pulmonary fibrosis is severe untreatable Professor Gary Anderson do not work well in patients suffering feature of some acute and chronic lung Dr. Andrew Jarnicki Chronic Obstructive Pulmonary Disease diseases, it has recently been recognised as (COPD). COPD afflicts 1 in 20 Australian a consequence of severe COVID-19-induced Project Availability and is the 5th leading cause of death pneumonia. Fibrosis is essentially scar tissue • PhD (AIHW 2019). Globally COPD afflicts more that replaces functional lung tissue and is a • Honours than 300 million people and is the third feature of Idiopathic pulmonary fibrosis (IPF) • Master of Biomedical Science leading cause of death. An overwhelming where it is progressive in nature and always proportion of disease burden is due to causes the demise of the patient. Fibrosis is Project: Pharmacokinetic and infection. It is now clear that there is a also observed in Acute Respiratory Distress pharmacodynamic analysis of strong reciprocal association between gut Syndrome (ARDS) where it develops rapidly, fluorescently tagged molecules with health and distal diseases, and that the does not usually progress but can leave different molecular weights in healthy manipulation of the gut microbiome and its patients with permanent lung damage and respiratory diseased mouse subsequent metabolite production affects and lifelong reduced physical capacity. models immunity and disease outcomes, including The current pre-clinical models of Aim of this project: To examine lung altering vaccine potency. Diet, antibiotic pulmonary fibrosis have a poor record permeability and cellular uptake to exposure, and smoking are the main in translating successful treatments different molecular weight molecules in factors affecting microbiota composition. from the laboratory to clinic, in part, due healthy and respiratory diseased mouse The aim here is to determine how diet can to their inability to mimic molecular or models in preparation for screening alter the gut microbiome, and how this cellular mechanisms that occur during therapeutic drug compounds. affects immune responses to a flu vaccine. tobacco smoking, viral infections and the Antibody production, critical early gene development of fibrotic lung diseases such Techniques: The student will learn animal expression and alterations in flu specific as IPF. We are interested in developing handling, tissue isolation and dissection. immune cell responses will be examined. pre-clinical models that better represent Histological skills including tissue these molecular and cellular mechanisms sectioning, staining and microscope Project supervisor imaging. Biochemistry skills including to improve and develop fibrosis treatments Dr. Andrew Jarnicki ELISA assay and western blotting. that will be successful in the laboratory and Project co-supervisors the clinic. Project supervisor Professor Gary Anderson Dr Joe Ciccotosto The aim of this project is to combine ‘wet lab’ Dr. Joe Ciccotosto methods with machine learning to improve Project co-supervisors Dr. Robert O’Donoghue the characterisation and quantification of Dr. Andrew Jarnicki Project Availability fibrosis in mouse models with real world Dr Robert O’Donoghue • PhD relevance to IPF and ARDS. You will use a Prof Gary Anderson • Honours number of laboratory techniques including • Master of Biomedical Science in vivo disease modelling, tissue culture, Project Availability QPCR, western blotting and FACs as well as • PhD machine learning methodologies using the • Honours facilities located within the Biological Optical • Master of Biomedical Science Microscopy Platform (BOMP). 11
CRACK AND TAYLOR GROUP Contact: Professor Peter Crack Email: pcrack@unimelb.edu.au Neurodegeneration Cell Signalling Location: Department of Pharmacology Neurotrauma Biomedical neuroscience and Therapeutics Neuroinflammation Infection and Immunity The Crack and Taylor group is run by Professor Peter Crack and Dr Juliet Taylor. The Neuropharmacology laboratory looks to understand how fundamental cellular signalling pathways can predispose the brain to exacerbated neurotrauma or neuropathology. In understanding how these pathways contribute to neural dysfunction we may be able to identify novel therapeutics that can be used to combat traumatic brain injury, Alzheimer’s disease and Parkinson’s disease. Project: Innate immunity, cytokines, prostaglandins, free radicals new targets for therapeutic intervention neuroinflammation and chronic and complement, which in turn induce into acute neurological conditions such neurodegeneration – a focus on chemokines and adhesion molecules, as stroke and neurotrauma and chronic Alzheimer’s disease recruit immune cells, and activate glial neurological diseases such as Alzheimer’s A major new area of research in our cells. Activation of the innate immune disease. laboratory is the role that the innate system is an important component of Skill acquisition: In vivo disease models, immune system plays in the progression this inflammatory response. We have histology, immunohistochemistry, of chronic neuronal pathology. It is now discovered that neuroinflammation morphometry, quantitative PCR, FACS appreciated that the central nervous is mediated by the generation of analysis of cell populations, cell and system (CNS) does exhibit features type-I interferons. Type-I interferons tissue culture, ELISA, molecular biology of inflammation, and in response to are the master regulators of the and western blotting. injury, infection or disease, resident neuroinflammatory response seen in CNS cells generate inflammatory Alzheimer’s disease. The molecular Project supervisor mediators, including proinflammatory mechanisms that are influenced by the Professor Peter Crack type-I interferon signalling comprises Project co-supervisor Dr Juliet Taylor Project Availability • PhD • Honours • Master of Biomedical Science 12
Project: Understanding traumatic Project: The use of bioactive matrices Project: The role of neuroinflammation brain injury to treat traumatic brain injury in Parkinson’s disease Traumatic brain injury (TBI) represents the Traumatic brain injury (TBI) Parkinson’s disease (PD) is a progressive major cause of death in young individuals represents the major cause of death neurological disease that is characterized in industrialised countries. Despite the in young individuals in industrialised by the loss of dopaminergic neurons, improvement of neurosurgical procedures countries. Despite the improvement primarily in the substantia nigra. The loss of as well as critical care management, of neurosurgical procedures as well as these neurons leads to a motor handicap, morbidity and mortality are still high critical care management, morbidity and associated depression, pain and general and approximately 25% of these patients mortality are still high and approximately decreased quality of life. The mechanism remain with permanent disabilities 25% of these patients remain with for the loss of the dopaminergeric neurons becoming a familiar, social and economic permanent disabilities becoming a is unknown although it is hypothesised burden for society. A better understanding familiar, social and economic burden that protein mis-folding, oxidative stress of events occurring in the brain after for society. There are no treatments and neuro-inflammation may contribute traumatic brain injury is essential available for traumatic brain injury. We to the cell death. We hypothesise that the to identify ways to limit the damage are investigating the use of biomaterials neuroinflammatory response triggers and ultimately improve the outcome. to re-direct the brain’s endogenous deleterious events (eg, oxidative stress and This project will focus on the role that neural stem cells to facilitate neural cytokine-receptor-mediated apoptosis), neuroinflammation plays in the progression repair after TBI. This project will potentiating dopaminergic cell death and of neural injury after TBI. By altering the determine whether reconstructing contributing to disease progression. This pathways that control neuroinflammation functional neural circuitry via cell-based project proposes to study the molecular by either molecular or therapeutic means therapies represents a viable, alternative and cellular events associated with we are able to influence the outcome after therapeutic strategy to improve clinical neuro-inflammation in an animal model TBI. The data generated by this project outcome. of PD with a focus on the involvement of will be used to further understand the neuro-inflammation in the progression Skill acquisition: In vivo disease models, molecular pathways that are changed in the of PD. There is a growing body evidence histology, immunohistochemistry, brain after TBI. that the gut plays a role in PD. This project morphometry, quantitative PCR, FACS will investigate this hypothesis using a Skill acquisition: In vivo disease models, analysis of cell populations, cell and combination of gut organoids and gut histology, immunohistochemistry, tissue culture, ELISA, molecular biology motility assays. A multi-disciplinary morphometry, quantitative PCR, FACS and western blotting. approach using an alpha-synuclein in vivo analysis of cell populations, cell and tissue Project supervisor mouse model of PD coupled with in vitro culture, ELISA, molecular biology, and Professor Peter Crack studies to investigate the specific molecular western blotting. pathways involved will investigate the Project co-supervisor Project supervisor role that neuro-inflammation plays in the Dr Juliet Taylor Professor Peter Crack progression of PD. Project Availability Project co-supervisor Skill acquisition: The techniques involved • PhD Dr Juliet Taylor in this project entail a mouse model of PD, • Honours immunohistochemistry, primary neural cell Project Availability • Master of Biomedical Science culture, ELISA, QPCR analysis, siRNA and • PhD western analysis and data analysis. • Honours • Master of Biomedical Science Project supervisor Dr Juliet Taylor Project co-supervisor Professor Peter Crack Project Availability • PhD • Honours • Master of Biomedical Science 13
Project: Neuroinflammation and Project: The bioinformatic analysis of its contribution to an autism-like neuroinflammatory pathways seen in phenotype Alzheimer’s and Parkinson’s disease There is growing evidence in the Neuroinflammation is increasingly literature that neuroinflammation plays being attributed to the causation and a role in cognitive function. Microglial exacerbation of both acute and chronic activation has been shown to be involved neuropathologies. The emerging field of in synapse formation and maintenance. bioinformatics will be used to identify Recent studies have suggested that proteins and signal transduction neuro-inflammation plays a growing role pathways that contribute to the in the pathogenesis of autism spectrum production of neuroinflammation. This disorder (ASD). Previous work from our project be largely in silico based and laboratory highlights that the type-I will utilize the skills that are provided by interferon (IFN) system is a master the core bioinformatics facility located regulator of neuroinflammation in both in the Melbourne Brain Centre under acute and chronic neuropathology. This the guidance of Dr Victoria Perreau. project will utilise a well-established This approach enables hypothesis genetic mouse model of autism and generation through leverage of investigate if there is any attributable genomic, transcriptomic, phenotypic effect to type-I IFN signalling in the and proteomic datasets to understand progression of the autism like phenotype complex systems. The student will focus in this mouse. on understanding complex interplay of signal transduction networks that control Skill acquisition: In vivo disease models, the neuroinflammatory response. histology, immunohistochemistry, morphometry, quantitative PCR, FACS Skill acquisition: Bioinformatics, systems analysis of cell populations, cell and biology, pathway analysis. tissue culture, ELISA, molecular biology Project supervisor and western blotting. Professor Peter Crack Project supervisor Project co-supervisors Professor Peter Crack Dr Juliet Taylor Project co-supervisors Dr Victoria Perreau Dr Juliet Taylor Project Availability A/Prof Elisa Hill • PhD Project Availability • Honours • PhD • Master of Biomedical Science • Honours • Master of Biomedical Science 14
CROUCH LABORATORY Contact: Assoc. Prof. Peter Crouch Neurodegeneration Biomedical neuroscience Email: pjcrouch@unimelb.edu.au Location: Department of Pharmacology Cancer in Biomedicine Therapeutics and translation and Therapeutics Molecular mechanisms of disease The focus of our research is to elucidate the biochemical basis of human disease. We study degenerative conditions of the central nervous system as well as a diverse range of cancers, and our overarching aim is to generate the information needed to help develop and test new therapeutic options and to improve patient outcomes through enhanced disease detection and characterisation. Recent significant achievements include bench-to-clinic translation of a new drug for motor neurone disease and a first of its kind method for imaging cancer. To achieve these outcomes, we utilise a and functionality of specific proteins with progressive multiple sclerosis may broad range of experimental paradigms, which we can relate to what we currently represent opportunity for therapeutic ranging from cells grown in culture know about the drug’s mechanism of intervention. We have therefore been through to direct examination of human action. An increased understanding examining tissue samples from people tissue. Our analytical approaches of these mechanisms will advance our who had progressive multiple sclerosis span fundamental techniques (enzyme understanding of the causes of motor and also from models of the disease. activity assays, gene expression analysis, neurone disease and also the opportunity We are using the information we have histology and western blotting) through for additional therapeutic intervention. generated from our motor neurone to highly sophisticated techniques such disease research to guide these analyses. Project supervisor as quantitative in situ elemental imaging More extensive analysis of multiple A/Prof Peter Crouch sclerosis tissue is needed to help us Project: Understanding the biochemical Project co-supervisor consolidate the connection between the basis of motor neurone disease Dr James Hilton two diseases and therefore to further Our team has identified an important assess the opportunity to treat the two biochemical change that occurs in tissue Project availability: using a single therapeutic strategy. afflicted with motor neurone disease, • PhD a fatal disorder of the central nervous • Honours Project supervisor system for which effective treatments • Master of Biomedical Science A/Prof Peter Crouch do not yet exist. Moreover, we have Project co-supervisor demonstrated that therapeutically Project: The connection between Dr James Hilton targeting this change is protective, and our motor neurone disease and drug is now in the initial stages of clinical Project availability: progressive multiple sclerosis testing. However, a better understanding • PhD Significant similarities exist between • Honours of how this biochemical change relates motor neurone disease and progressive • Master of Biomedical Science to the decline of functional motor forms of multiple sclerosis. In pursuing neurones is still required. We are therefore our motor neurone disease research, we examining changes to the abundance established that some of the similarities 15
Project: Capturing the elemental Project: Elucidating the cellular signature of human disease mechanisms of human disease in vitro All biological material is defined by its Determining the biochemical changes elemental constituents (carbon, sulphur, that occur in human disease-affected phosphorous, etc.) and the onset and tissue is an essential part of our research, progression of human disease can but analysing human tissue is rarely therefore be detected and characterised amenable to the level of experimental by measuring changes to the abundance manipulation that is needed to elucidate and anatomical distribution of these the cellular mechanistic pathways that elements. We measure these changes cause the disease. In our laboratory we using a quantitative elemental imaging therefore complement our human tissue technique known as laser ablation analyses with cell culture experiments inductively coupled plasma mass in which specific phenomena can be spectrometry (LA-ICP-MS). We analyse controlled and examined in detail. We sections of biological material via LA- grow cells in the laboratory then we ICP-MS and the information generated expose them to the conditions needed to provides an ‘elemental image’ of the induce a response comparable to what disease. We use LA-ICP-MS to identify we have identified in the human disease. the presence of disease (e.g. tumour By analysing the treated cells, we are detection), to determine the biochemical able to systematically map the sequence basis of disease (e.g. changes in an of events that lead to disease. This work elemental co-factor required for specific is essential for identifying and validating enzyme activities), and to monitor drug therapeutic targets. uptake and biodistribution. Project supervisor Project supervisor A/Prof Peter Crouch A/Prof Peter Crouch Project co-supervisor Project availability: Dr Jeff Liddell • PhD • Honours Project availability: • Master of Biomedical Science • PhD • Honours • Master of Biomedical Science 16
GUNDLACH GROUP Contact: Professor Andrew Gundlach Neurobiology Cell Signalling Email: andrew.gundlach@florey.edu.au Location: The Florey Institute of Neuropharmacology Biomedical neuroscience Neuroscience and Mental Health Weblink: go.unimelb.edu.au/5b8r Therapeutics and Neuropsychiatry translation My laboratory seeks to increase our understanding of the neurobiology of neuropeptide/G-protein-coupled receptor (GPCR) systems in health and disease, with the goal of identifying the physiological role of key neural networks in the brain and developing novel therapeutics for neuropsychiatric disorders. A primary focus of current projects involving several international collaborations is the relaxin-3/RXFP3 system, and the inhibitory (GABA) projection- and inter-neurons that express the peptide and its receptor. New initiatives are targeting the unexplored relaxin/RXFP1 system in brain and its possible roles in neurovascular coupling and sensory/cognitive processing; and the role of the signalling enzyme, CaMKK2 in regulation of brain and behaviour. Projects on these topics will provide training in techniques such as neurochemical phenotyping of target neurons, cell signalling, neuropharmacology, physiology and behaviour. Project: Relaxin-3/RXFP3 signalling insomnia, anorexia, obesity, drug abuse, Project co-supervisors in control of arousal and complex chronic pain and depression. In a new Dr Mathias Dutschmann physiology and behaviour initiative, we are also exploring the A/Prof Akhter Hossain Neural arousal pathways facilitate potential interaction of RXFP3 and opioid Project availability: heightened awareness, attention and signalling in the brainstem, in relation to • PhD cognition, and are also implicated in opioid-induced respiratory suppression. • Honours reward signals associated with food- and Studies so far have examined the • Master of Biomedical Science drug-seeking behaviour. Established impact of pharmacological treatments arousal transmitter systems include on respiratory networks, and studies serotonin neurons in the raphe nuclei, are now required to determine the Project: Rare cortical projection- dopamine neurons in the ventral relative neuroanatomical distribution neuron function in arousal, sleep and tegmental area, and orexin (peptide) of the relevant RXFP3 and opioid neuropathology neurons in the lateral hypothalamus. receptor systems to assess the direct or Experimental and in silico data suggest Anatomical and functional studies also indirect (network-based) nature of the brain relaxin/RXFP1 signalling regulates suggest relaxin-3 neurons in nucleus interactions observed. Projects on this neural networks that contribute to incertus (NI) (image) and the central topic will provide training in techniques arousal, attention, memory, and sensory grey (CG) represent an arousal pathway such as neurochemical phenotyping of processing; and key characteristics that modulates behaviours such as neurons (image), neural tract-tracing, cell of cortical ‘relaxin’ neurons and their feeding, attention (vigilance), motivation signalling detection, neuropharmacology, RXFP1-positive target cells have been and exploration. Therefore, relaxin-3/ physiology and behaviour. revealed. In mouse cortex, relaxin (not RXFP3 systems represents a potential Rxfp1) mRNA is expressed by long- Project supervisor target for treating conditions such as projecting (somatostatin/GABA) neurons, Professor Andrew Gundlach which we hypothesise are capable of morphological, neurochemical and synaptic plasticity in response to specific neural inputs and to acute and chronic brain injury. In contrast, Rxfp1 mRNA is expressed by topographically-distributed inhibitory and excitatory neurons in outer and deep cortical layers which are likely targeted by adjacent or distant relaxin neurons, but their nature and function are otherwise uncharacterised. Thus, this project will investigate populations of cortical neurons that synthesize the peptide, relaxin, and their Nucleus incertus neurons contain relaxin-3 peptide (green) and calcium-binding proteins (red/blue) target neurons that express the neural 17
membrane receptor, RXFP1. We propose Project: CaMKK2 control of neuronal to lithium. We will also determine the relaxin/RXFP1 signalling in areas containing function and complex behaviour in neuroanatomical distribution of CaMKK2 sensory, emotional and cognitive circuits health and disease within specific types of neurons (image) regulates processes, including nerve Our research has revealed that Ca2+- and neural circuits, and the impact of growth and modification of synapses and calmodulin dependent protein kinase altered CaMKK2 signalling on specific the surrounding environment, with links to kinase-2 (CaMKK2) is a key regulator downstream targets. These studies sleep/wake states, and responses to brain of neuronal function and associated will provide an improved mechanistic injury. We will assess the gene/protein complex behaviour. Mutations that understanding of CaMKK2 function, expression profile of relaxin- and RXFP1- reduce CaMKK2 expression or activity which is essential to advance our positive neurons in mouse brain (image), display a strong association with a fundamental biological knowledge of and the impact of perturbations such as spectrum of human psychiatric disorders, this key neuronal enzyme system, and sleep deprivation and brain pathology including anxiety, bipolar disorder and to inform novel treatment strategies for on this profile. In collaborative studies, schizophrenia, indicating that optimal multiple psychiatric conditions. we will also explore how relaxin alters CaMKK2 activity is essential for normal, Project supervisor the electrical activity of RXFP1-positive healthy brain development and function. Professor Andrew Gundlach cortical neurons in mice. These studies Notably, the mood-stabilising drug, should reveal the therapeutic potential lithium, a major therapy for multiple Project co-supervisor of a specific brain receptor system for psychiatric illnesses, activates CaMKK2. Dr John Scott alleviating cognitive and emotional Therefore, understanding central Project availability: symptoms in neurological disorders. CaMKK2 signalling is of significant • PhD Project supervisor translational interest. • Honours Prof Andrew Gundlach However, the neurobiology of CaMKK2, • Master of Biomedical Science Project co-supervisors including its upstream regulatory Dr Laura Jacobson inputs, and its downstream signalling Dr Mohsen Nategh and neural network effects in brain are not fully understood. In this project, Project availability: we will study the behavioural profile • PhD of mice with targeted mutations of a • Honours regulatory site in CaMKK2 in a range of • Master of Biomedical Science validated behavioural assays, as well as the responsiveness of these mice Relaxin mRNA (red) and nNOS mRNA (green) in a rare CaMKK2 mRNA (white) and BDNF mRNA (green) in excitatory (vGlut2 mRNA, red) neurons in hippocampus somatostatin neuron (white) in cerebral cortex 18
MACKAY GROUP Contact: Dr Graham Mackay Neuroinflammation Infection and Immunity Email: gmackay@unimelb.edu.au Location: Department of Pharmacology Therapeutics and Lung Health and Therapeutics translation Cell Signalling Our team is focussed largely around the fascinating mast cell and its role in allergic and non-allergic disease. In particular, we want to better understand how these cells are activated, the mediators they release and if we can translate this knowledge to generating new therapeutics. Project: The role of mast cell-derived Project: MRGPRX2-mediated drug macrophage migration inhibitory hypersensitivity drug reactions. factor (MIF) in Alzheimer’s disease Exciting new work has identified that mast Macrophage migratory inhibitor factor cells have a receptor called MRGPRX2 (MIF) is a multi-functional cytokine that that can be directly activated by many has both intracellular and extracellular clinically used drugs including certain actions and possesses enzymatic activity antibiotics. This might explain a significant alongside the ability to stimulate its number of drug hypersensitivity reactions. receptor. In this project you will examine However, it is unclear as to why only some the stimulus-induced release of MIF from individuals react so adversely to these immune cells that are thought to play an drugs. In this project you will examine important role in Alzheimer’s disease (AD) mast cell activation through MRGPRX2 pathology, with a focus on the mast cell. and identify pathways that enhance the You will also examine the expression of activity of this pathway. This information MIF in samples taken from animal models will hopefully be of utility in better of AD and from patients with the disease. understanding, predicting and treating Combined, the project will lead to a better MRGPRX2-mediated drug hypersensitivity. understanding of the role of MIF in driving Project supervisor the inflammatory neurodegeneration Dr Graham Mackay observed in AD. Project availability: Project supervisor • PhD Dr Graham Mackay • Honours Project co-supervisor • Master of Biomedical Science Prof Peter Crack Project availability: • PhD • Honours • Master of Biomedical Science 19
PETER AND WANG GROUP Contact: Professor Karlheinz Peter Cardiovascular Therapeutics and Email: karlheinz.peter@baker.edu.au pharmacology translation Location: Baker Heart and Diabetes Drug design Molecular imaging Institute Weblink: http://go.unimelb.edu.au/6ngj Translational and Targeted drug delivery clinical research The Peter and Wang group focuses on basic and translational research covering a wide variety of themes, including cardiovascular disease, autoimmunity and cancer. We study fundamental disease mechanisms in order to define the key cells and molecules which contribute to the development or outcome of disease. Using this information, we then design, test and implement novel molecular imaging approaches using state of the art technologies (magnetic resonance imaging, ultrasound, computed tomography, positron-emission tomography and 3D fluorescence emission computed tomography). We focus on novel therapeutic approaches, such as biological therapies targeting immune cells; and theragnostics, which combine both therapeutics and diagnostics into a single platform. Project: Diagnosis and therapy Aims: This project aims to investigate Project: Activated platelet-targeted of inflammatory diseases using whether VCAM-1 targeted contrast agents drug therapy molecular imaging will enhance inflamed vessels using Acute thrombosis causes vessel occlusion Cardiovascular diseases, such as heart molecular imaging, thereby providing and results in ischemic complications, attacks and strokes, are major causes a better diagnostic technology. By such as myocardial infarction and stroke. of death and disability in Australia and harnessing the targeting ability of the Therefore, it is a major cause of death and worldwide. These events are caused by antibodies, we can then conjugate drugs disability. chronic inflammation, atherosclerosis onto these antibodies for side-effect free, targeted drug delivery. Anti-coagulation and anti-thrombotic and acute thrombosis. drugs are valuable alternatives for the The use of small recombinant antibodies Significance: With steadily increasing treatment of these acute events where for diagnostic molecular imaging health care expenses, a promising invasive/surgical procedure is not and targeted drug delivery are well translational imaging application can available in a timely fashion. However, established in our lab. This project would fulfil the need for a cost-effective and the current clinically approved anti- focus on the Vascular Cell Adhesion non-invasive diagnostic tool. Employing coagulation and anti-thrombotic drugs Molecule-1 (VCAM-1), which is an a targeted drug delivery approach will have significant drawbacks, including endothelial surface molecule that is most enable treatment of inflammation that bleeding complications. Thus, their use strongly and specifically upregulated may prevent downstream catastrophic is highly restricted leaving many patients during inflammation. For this reason, events of heart attacks and strokes. untreated. The use of small recombinant this molecule has been chosen as an Project supervisor antibodies for diagnostic molecular additional target epitope for molecular Dr Xiaowei Wang imaging and targeted drug delivery is well imaging of inflammation. We propose to established in our lab. conjugate VCAM-1 targeting recombinant Project co-supervisor Prof Karlheinz Peter This project would focus on the antibodies to different contrast agents development of novel targeted drugs that for their respective imaging modality. We Project availability: are directed against activated platelets. would use these recombinant antibodies • PhD for diagnostic imaging and targeted • Honours When thrombosis occurs, there is a delivery of pharmacological treatment. • Master of Biomedical Science thunderstorm of platelet activation Our group has access to a variety of and aggregation. Our targeted drugs clinically available imaging modalities, will locate these activated platelets including magnetic resonance imaging and accumulate at the site of the clot. (MRI), ultrasound, computed tomography This allows a high potency of drugs (CT) and positron-emission tomography for efficient and safe thrombolytic (PET), as well as latest preclinical treatment. Due to the targeting scanners, such as new 19-Flourine MRI properties, we can reduce the overall technology and 3D fluorescence emission number of drugs needed, therefore there computed tomography (FLECT). would only be a small concentration of drugs circulating in the blood. This would also enable us to eliminate the current bleeding complications. 20
Significance: This novel targeted agent Project supervisor Aims: This project aims to investigate promises to overcome the current Dr Yung Chih Chen activated platelet targeted contrast limitations of bleeding complications agents for detection of inflammation, Project co-supervisor associated with the clinical thrombolytic cancer and/or thrombosis using Prof Karlheinz Peter therapy. It has the potential to break molecular imaging, thereby providing the fatal link between increased drug Project availability: a better diagnostic technology. By potency and bleeding complications. • PhD harnessing the targeting ability of the • Honours antibodies, we can then conjugate drugs Project supervisor • Master of Biomedical Science onto them for side-effect free, targeted Dr Xiaowei Wang drug delivery. Project co-supervisors Project: Diagnosis and therapy of Significance: With steadily increasing Prof Karlheinz Peter cancer, inflammation and thrombotic health care expenses, a promising Dr Laura Bienvenu diseases. translational imaging application can Project availability: Activated platelets have been shown fulfil the need for a cost-effective and • PhD to play an important role in cancer, non-invasive diagnostic tool. Employing • Honours inflammation and thrombotic diseases. a targeted drug delivery approach will • Master of Biomedical Science enable treatment of thrombosis. This project would focus on Glycoprotein (GP) IIb/IIIa, which plays an important Project supervisor Project: Understanding the role of the role in the aggregation of platelets. Prof Karlheinz Peter microbiome in chronic cardiovascular GPIIb/IIIa is the most abundant platelet inflammation Project co-supervisor receptor and it undergoes a change in Dr Xiaowei Wang In recent years it has been demonstrated confirmation when activated. For this that the microbiome, composed of reason, this molecule has been chosen Project availability: trillions of microbes inhabiting our as the target epitope for molecular • PhD bodies, can significantly influence imaging. The use of small recombinant • Honours disease susceptibility and severity. antibodies for diagnostic molecular • Master of Biomedical Science Mechanistically, the microbiome has imaging and targeted drug delivery been shown to elicit this influence are well established in our lab. We by regulating metabolism and the propose to conjugate activated GPIIb/ immune system. Atherosclerosis is IIIa targeting recombinant antibodies a disease of chronic inflammation to different contrast agents for their and metabolic dysfunction, however, respective imaging modality. These whether the microbiome plays a role in recombinant antibodies can be used for determining an individual’s susceptibility both diagnostic imaging and targeted to atherosclerosis or the disease’s delivery of pharmacological treatment. severity is unknown. This project will Our group has access to a variety of explore the role of the microbiome in clinically available imaging modalities, the development of atherosclerosis including magnetic resonance imaging with a key focus on how the microbiome (MRI), ultrasound, computed tomography influences the immune system. In (CT) and positron-emission tomography addition, this research will define and (PET), as well as the latest preclinical test strategies for the therapeutic scanners, such as new 19-Flourine MRI manipulation of the microbiome in the technology and 3D fluorescence emission context of atherosclerosis and chronic computed tomography (FLECT). inflammation. 21
Project: Developing nanoparticles Project supervisor 1. Deep characterisation of adaptive for targeted theragnostic delivery of Dr Xiaowei Wang immune responses in human and drug and gene therapeutics . Project co-supervisor murine cardiovascular disease. Cardiovascular disease (CVD) is the Prof Karlheinz Peter 2. Defining the role of sexual dimorphism leading cause of mortality worldwide. in the immune response in Atherosclerosis, a chronic inflammatory Project availability: cardiovascular disease. disease, is the underlying cause • PhD of most CVDs. Therefore, early • Honours 3. The role of conventional vs detection, prevention or regression of • Master of Biomedical Science unconventional T cells in atherosclerosis may prevent devastating atherosclerosis and myocardial events such as heart attacks from Project: Immunity, Chronic infarction. occurring. We will create bio-compatible Inflammation and Cardiovascular 4. Modulating adaptive immunity for the nanoparticles as contrast agents for Disease treatment of cardiovascular disease. imaging and drug carriers. These Atherosclerosis is a disease characterised nanoparticles gives us the flexibility Project supervisor by the formation of chronically inflamed Prof Karlheinz Peter to incorporate drugs to increase their lipid laden plaques in medium and large payload and/or apply them in gene arteries, such as those that supply the Project co-supervisor delivery. By targeting these nanoparticles heart and brain with blood. The rupture Dr Jonathan Noonan to the biomarkers of atherosclerosis, we of these plaques causes blood clots can investigate their functions as novel Project availability: which can block these arteries and is the theragnostic (simultaneous diagnosis • PhD primary cause of myocardial infarction and therapy) approaches. Therefore, • Honours (heart attacks), strokes, and most of this project would also focus on Vascular • Master of Biomedical Science the cardiovascular disease mortality. Cell Adhesion Molecule-1, which is one of Despite recognition that inflammation the endothelial surface molecules most is a key feature of atherosclerosis and strongly and specifically up-regulated in the most likely cause of plaque rupture, inflammation. We propose to conjugate it is not fully understood what drives VCAM-1 targeting recombinant antibodies the chronicity of pro-atherosclerotic onto nanoparticles for diagnosis imaging immune responses. With a focus on the and targeted delivery of pharmacological adaptive immune system (T & B cells); we or genetic treatment. Significance: With aim to deeply characterise the immune steadily increasing health care expenses, landscape in atherosclerosis using targeted theragnostic nanoparticles can state-of-the-art technologies, identify provide early diagnosis and treatment the causes of immune dysregulation and of atherosclerosis, thereby preventing chronic atherosclerotic inflammation further CVDs. and define the role these pathways play in the development and outcome of cardiovascular disease. There is the opportunity to pursue several avenues for research projects, including: 22
SCHNEIDER-FUTSCHIK GROUP Contact: Dr Elena Schneider-Futschik Lung Health Neuropharmacology Email: elena.schneider@unimelb.edu.au Location: Department of Pharmacology Cardio-Respiratory Infection and Immunity & Therapeutics The Cystic Fibrosis Pharmacology group is are interested in the mechanisms of drug action, drug-drug interactions and drug safety of cystic fibrosis drugs during pregnancy and breastfeeding. Project Cystic fibrosis receptors Project: Cystic fibrosis and during developmental stages inflammation The cystic fibrosis modulators have In this study, we will correlate the transformed clinical outcomes for many functional manifestations of cystic CF patients by improving survival and fibrosis with pathological changes in general health. However, the much histopathology; and investigate whether greater prevalence of CF women reaching administration of ivacaftor, the first CF childbearing age means increasing gene modulator that has significantly numbers of women taking these improved the life of patients with CF; is medications face very difficult decisions beneficial in improving inflammation. when it comes to having a family. This Project supervisor study will aid clinicians in prescribing Dr Elena Schneider-Futschik CFTR modulators to pregnant women on how these drugs will transfer across Project availability: essential barriers during different • Honours developmental stages. Project supervisor Dr Elena Schneider-Futschik Project co-supervisor Norman Saunders Project availability: • Honours • Master of Biomedical Science 23
You can also read