What's On at UWA

The Seminar: Obesity and non-alcoholic fatty liver disease (NAFLD) are major health problems in Australia. All are characterised by an initial accumulation of lipids which, along with the contribution of confounding factors, such as iron, can lead to organ dysfunction and death. In the presence of existing fat deposits, iron has been linked to progression of NAFLD, via the production of free radicals. Recently we have shown that iron may be involved in the initial lipid accumulation by stimulating production of cholesterol in the liver. Importantly, this cholesterol may accumulate in the mitochondria; mitochondrial cholesterol accumulation has been associated with NAFLD. These data are consistent with an increase in total hepatic lipid burden and a role for iron in the early stages of fatty liver disease

The Speaker: Ross completed his PhD in Physiology at UWA in 1997 studying non-transferrin bound iron uptake in the liver. He retained his interest in metal metabolism following his move to London in 1998, working at the University of London where he studied the synthesis of vitamin B12 in Pseudomonas aeruginosa, the pathogen which causes many lung infections in cyctic fibrosis patients. In 2004, he returned to Western Australia to work in the School of Medicine & Pharmacology, UWA, continuing his work on iron in the liver, focussing on the role of transferrin receptor 2 in iron uptake and how mutations in this protein cause a rare form of the iron-loading disorder, haemochromatosis. This work led to identification of a role for iron in the biosynthesis of cholesterol, implicating iron as a factor in liver disease and obesity. In 2011, he moved to Curtin University where he is continuing his research into liver iron and its effects on other metabolic processes.

Binuclear metallohydrolases are a functionally diverse class of metalloenzyme whose members require two closely spaced metal ions in their active site to catalyse the hydrolysis of amides and phosphate esters [1].

Purple acid phosphatases (PAPs) are found in animals, plants and fungi. They catalyse the hydrolysis of a broad range of phosphate esters and anhydrides under acidic conditions. PAPs contain an Fe(III) and a divalent metal ion in their active site. In animals, they are responsible for bone resorption in osteoclasts, and there is substantial evidence to support the role of PAPs in osteoporosis, a disease characterised by excessive bone resorption. PAP is, therefore, an attractive target for the development of drugs to treat this debilitating condition [1].

β-Lactam-containing antibiotics such as penicillins, cephalosporins and carbapenems, are the most widely used drugs for the treatment of bacterial infections. A large number of pathogenic bacteria are now producing metallo-β-lactamases (MBLs), enzymes that hydrolyse the β-lactam rings of nearly all known classes of β-lactam-containing antibiotics, and so make these bacteria resistant to these drugs. MBLs contain two zinc(II) ions in their active sites. As yet, there are no clinically useful antagonists of MBLs, and so bacteria expressing these enzymes pose a significant risk to human health.

This presentation will describe a multidisciplinary approach to the development of drug leads against PAP and MBL. Our approaches to the development of enzyme inhibitors have been twofold. In the first approach we have use the crystal structures of PAPs and MBLs to rationally design ligands to bind to the binuclear metal centre of the active sites, and to maximise non-covalent interactions at locations proximal to the active site [2,3]. In the second approach we have used fragment-based screening to identify small molecule inhibitors of PAP, and we have obtained crystals structures of these complexed in the active site of the enzyme [4]. These studies have led to development of the most potent PAP inhibitors yet reported.

[1] Schenk, Mitic, Gahan, Ollis, McGeary & Guddat, Acc. Chem. Res., 2012, 45, 1593. [2] Mohd-Pahmi, Hussein, Schenk & McGeary, Bioorg. & Med. Chem. Lett., 2011, 21, 3092. [3] Faridoon, Hussein, Vella, Ul Islam, Ollis, Schenk & McGeary, Bioorg. & Med. Chem. Lett., 2012, 22, 380. [4] Feder, Hussein, Clayton, Kan, Schenk, McGeary & Guddat, Chem. Biol. & Drug Des., 2012, In Press. doi: 10.1111/cbdd.12001

Our group is interested in developing highly active water oxidation catalysts for incorporation into (photo)-electrochemical water splitting devices. Inspired by the only water oxidation catalyst known to be active in vivo, the Mn4Ca1O5 cluster found in Photosystem II (PSII), we initially imbedded tetranuclear Mn complexes into Nafion films and demonstrated sustained water oxidation catalysis in vitro on illumination with visible light and application of a bias.1 By combining these photoanodes with a ruthenium(II) sensitiser into a photo-electrochemical cell water oxidation was achieved using visible light as the only energy source, as occurs in PSII.2 Examination of the fate of the Mn cluster during catalysis using X-ray Absorption Spectroscopy (XAS) and Transmission Electron Microscopy (TEM) revealed that it dissociates in Nafion forming MnII species which, on application of a bias, are oxidized to MnOx nanoparticles (detected by TEM). These are reduced on illumination and O2 is concurrently released.3 Recent EPR studies support the catalytic cycle proposed from the XAS studies. Thus, water oxidation catalysis does not involve the original cluster. The observed cycling between photo-reduced MnII species and the Mn-oxide parallels the well-known biogeochemistry of Mn where MnIII/IV oxides, formed by oxidative processes, are photoreduced to Mn2+ in sunlight. Given that catalysis did not involve the original Mn4O4 cluster, catalytic activity was expected to be independent of the Mn precursor. To our surprise, however, an examination of a series of Mn complexes found that the size, crystallinity and catalytic activity of the MnOx nanoparticles varied with precursor used to generate them. The presentation will also cover our recent research exploring various approaches for the deposition of catalytically active metal oxide films, including the application of ionic liquids.

All welcome to attend the School of Pathology & Laboratory Medicine 2012 Seminar Series (RPH). On a weekly basis we have local/guest speakers presenting to a wide audience typically in the fields of immunology, molecular biology and cancer related research. This week we are privileged to have a local speaker. Professor Charles Bond from the School of Chemistry and Biochemistry, University of Western Australia presenting on "Structural studies of gene regulatory protein in eukaryotes". The event is sponsored by Life Technologies and light refreshments are provided. For further inquiries please contact using the provided email. Look forward to seeing you there!

The Seminar: Promotion of lung volume recruitment in atelectatic lung and maintenance of existing recruited lung are vital goals of contemporary ventilatory support. In the mature lung, the recruitment of terminal airspaces are governed by power-law distributions, arising from avalanches associated with threshold pressure phenomena propagating down a branching tree structure. There is increasing evidence that the superimposition of noise on the pressure waveform during conventional can promote recruitment of collapsed lung zones when the peak inspiratory pressure is at or around the lower inflexure and that this approach may also promote production of endogenous surfactant. The mechanism likely involves the phenomenon of stochastic resonance. Stochastic resonance is most simply described as the addition of noise to a weak input signal to enhance output in a nonlinear system. It is a widespread, naturally occurring phenomenon that can be seen reflected in the patterns of world weather, fluctuations on the stock market, population biology, and optimal functioning of neural networks, to name but a few. The essential ingredients for stochastic resonance are a nonlinear dynamic system, a weak biologic signal, and superimposed noise. Recent studies comparing variable to constant volume and rhythm ventilation patterns in newborn lambs demonstrate a physiological advantage of variable input for lung volume recruitment, and upregulation of surfactant protein and developmental genes, suggesting that the newborn lung is programmed to respond to variability, and that variability may confer survival advantage. The Speaker: Professor Jane Pillow is a clinical academic neonatologist at the University of Western Australia and Co-Director of the newly formed UWA Centre for Neonatal Research and Education. She is acknowledged internationally as an expert in the area of neonatal respiratory physiology and mechanical ventilation. Prof Pillow is internationally renowned for her particular expertise in high-frequency ventilation, having undertaken completed her PhD thesis in 2000 on “Optimising High-Frequency Oscillatory Ventilation in Neonates”. Since completing her PhD with Distinction in 2000, Prof Pillow’s research interests have expanded to include high-frequency jet ventilation, variable ventilation, bubble CPAP, patient triggered ventilation and minimising lung and diaphragmatic injury during resuscitation. Her research group in Perth undertakes animal studies using the preterm lamb as a model of neonatal respiratory distress syndrome, many of which are performed in collaboration with interstate and international colleagues in medical, physiological, anatomical and biomedical engineering departments. Future plans for the lamb work include the development of a preterm lamb intensive care unit for long term ventilation of preterm lambs. At KEMH, Professor Pillow also runs a neonatal lung function laboratory, and is involved in clinical trials and follow-up functional studies of children born prematurely in addition to involvement in clinical trials. Jane has obtained over $4.5 million AUD in research funding, including 4 grants from the NHMRC (3 as CIA) and 3 grants from the NIH and has had continuous scholarship and fellowship funding from the NHMRC and Viertel Foundation since 1997. She has extensive involvement in peer-review activities relevant to neonatal research, mechanical ventilation and respiratory physiology. In addition to her academic responsibilities, Prof Pillow is a Consultant Neonatologist in the Women’s and Newborn’s Health Service. She is currently based within the UWA Centre of Neonatal Research and Education and the Neonatal Clinical Care Unit at King Edward Memorial Hospital in Perth, which has 100 neonatal beds including 30 bed NICU, but which caters frequently for up to 40 infants on mechanical ventilation or CPAP.

Luminescent species find applications in a wide variety of fields, including optical technologies and devices, sensors, biomedical diagnostics and many more. Our group is interested in the design of transition metal and lanthanoid coordination compounds that possess phosphorescent properties, as well as their use in materials and life science. This presentation will illustrate efforts within our research group centred on the synthesis of organometallic tetrazolato metal complexes and the investigation of their photophysical properties. As these complexes exhibit efficient luminescent properties, we have also assessed their cellular incubation and cytotoxicity, and the results highlight these species are promising candidates for the design of improved cellular labels. More recent results on the use of N-heterocyclic carbene ligands for the construction of luminescent metal complexes will also be presented.

Complex I has several unique features in plants. Most notably, it includes 15 extra subunits, some of which introduce side activities into this respiratory enzyme. For example, subunits resembling an archaebacterial gamma-type carbonic anhydrase form an integral part of complex I in plants. These carbonic anhydrase subunits constitute a spherical extra domain which is attached to the membrane arm of complex I on its matrix exposed side. Furthermore, L-galactono-1,4 dehydrogenase (GLDH), which catalyses the terminal step of ascorbate biosynthesis in plants, is associated with complex I in plants. Novel data on the structure of the NADH dehydrogenase complex and its multiple functions in plant cells will be presented and discussed.

LIWA invites you to a free seminar on: "Tumour suppressor activity of microRNA-7 and microRNA-331-3p" by Dr Keith Giles, Postdoctoral Research Associate, Western Australian Institute for Medical Research (WAIMR). Time: 12 noon for light lunch with 12.30pm – 1.30pm presentation.

The Seminar: It is generally thought that lung growth follows a trajectory such that an early life deficit in lung function is maintained throughout life. This has important implications for the development of chronic lung disease whereby early life impairments in lung growth may decrease the threshold for the development of respiratory symptoms, while increasing the susceptibility to insults that exacerbate disease. As such it is critical that we understand the environmental factors that impair (or promote) lung growth in early life in order to inform public health initiatives that will improve long term lung health in the community. This presentation will discuss the importance of in utero and early life environmental exposures in modulating lung development and the susceptibility to chronic lung disease using two case studies: 1) arsenic exposure via drinking water in utero and 2) vitamin D. While arsenic and vitamin D work in opposing directions, with arsenic having a negative impact on lung development and vitamin D having a positive impact, they are both associated with chronic lung disease in later life and can be modified through public health interventions. The impact of these exposures on lung development will be discussed in light of our recent studies using mouse models.

The Speaker: Associate Professor Graeme Zosky is a Principal Investigator and Head of the Lung Growth and Environmental Health Group at the Telethon Institute for Child Health Research. He has a PhD in Zoology from U.W.A. (2003) and a Masters in Biostatistics from the University of Sydney (2010). His research focuses on the role of early life exposures in the development of chronic lung disease later in life. He is also an international leader in the design and application of novel techniques for assessing lung mechanics in laboratory animals.

The beauty of electrochemistry at liquid-liquid interfaces is that it enables the detection of ions or ionisable species by ion-transfer reactions. As a result, problems associated with the detection of analytes by oxidation/reduction reactions at solid electrodes can be surmounted. These problems may include an inability to easily oxidise/reduce the target analyte(s), the simultaneous oxidation/reduction of interferences, or electrode fouling by reaction products. Proteins are extremely important analytical targets because of their roles in regulating biological processes and the fact that diseases often result in changes in protein behaviour. Such altered protein behaviour leads to these biomacromolecules becoming markers or indicators of that disease, so-called biomarkers. Not all proteins are redox-active and even redox-active proteins cannot always be easily detected by oxidation or reduction at a metal or carbon electrode. For this reason, the electrochemical behaviour and electrochemical detection of proteins via ion-transfer reactions at the interface between two immiscible electrolyte solutions (ITIES) has been of growing interest. This presentation will discuss the main idea that electrochemistry at liquid-liquid interfaces enables the detection of ions via non-redox reactions, which may be applied to detection of proteins. Recent progress towards achievement of nanomolar detection of proteins as well as formation and characteristics of nanoscale liquid-liquid interfaces will be presented.

My research shows that the chemical mimicry crucial to sexual deception is responsible for reproductive isolation and potentially even speciation. I also show through mating system analysis and studies of wasp behaviour that this strategy is a superbly adaptive solution to the problem flowers face of simultaneously attracting pollinators before persuading them to leave quickly.

An educational seminar day that will address local and global problems relating to infection control. Topics include antibiotic resistance and stewardship, superbugs, Clostridium difficile,viruses and pandemics, workplace sterilization, sharp safety and immunisation scheduling.

An educational seminar day that will address local and global problems relating to infection control. Topics include antibiotic resistance and stewardship, superbugs, Clostridium difficile,viruses and pandemics, workplace sterilization, sharp safety and immunisation scheduling.

Applications CLOSE 30th November for the Science Experience 2013. Current year 9 and 10 students apply on-line at the Science Experience website. Late applications will be accepted if a place is available. To check whether a program is fully booked at any time go to www.scienceexperience.com.au/when-where/wa

The Science Experience is a three day program of events for students about to enter Year 10 and Year 11. The program is held Tuesday 15th - Thursday 17th January 2013 and is designed to excite students about science and technology and introduce the students to the variety of career options in science and engineering, with the aim that more will choose to study and pursue a career in science.

Controversy continues to surround national student assessment in Australia. However, I argue that testing is neither good nor bad: the devil lies in what people – teachers, school, systems and even parents – do about the tests and the data they generate. I report the experiences of principals, teachers and curriculum consultants in one educational authority to describe how responsibility for interrogating, interpreting and applying data has gradually shifted from an external top-down approach to an internal bottom-up model in a planned, sustained and centrally supported manner, during the past eight years.

Carbon nanostructures have been the topic of two Nobel prizes to date, Chemistry in 1996 (fullerenes) and Physics in 2010 (graphene), but carbon’s versatile bonding has resulted in the discovery of a wide range of other exotic nanoforms. We will take a quick safari through this jungle of bamboos, peapods, nanohorns, scrolls, nanobuds, etc. To help make sense of this bewildering array of forms I will propose a nomenclature based on their structure.

The underlying structural differences of each carbon nanoform can fundamentally alter their reaction chemistry and mechanical and electronic properties. Using first principles calculations I will examine specific examples where these effects modify the underlying chemistry and physical properties of these materials, such as their oxidation behaviour and mutual interaction. As well as giving unique insight into experimental results, such calculations can predict fascinating new behaviour and open up undiscovered pathways for synthesis and post-processing.

As the world population grows and we are facing a 70% increase of food demand over the next four decades,the need to retain versatile and productive soils for food production and to maximise the output from the land is one of the most important issues of our time. This symposium will bring together world leading soil scientists to highlight the importance of soil health, from a national and global food security perspective. They will examine the role which science, technology and innovation can play in supporting Australian farmers in maintaining and developing healthy soils to achieve productivity gains and sustainable agricultural production. To participate in this workshop register online via www.soilhealthwa.eventbrite.com.au

The Seminar: With ageing, the progressive loss of skeletal muscle mass and function (sarcopenia) results in frailty, loss of independence and is a major cause of increased falls and fractures. Surprisingly little is known about the mechanisms of sarcopenia and these will prove to be complex. We have established a mouse model of sarcopenia and described the time course of age-related muscle wasting in C57Bl/6J mice. This model is currently used to investigate mechanisms of age-related muscle wasting. The talk will focus on three aspects of sarcopenia: 1) understanding molecular changes in ageing muscle with the aim to identify sarcopenia markers and develop therapies; 2) loss of myofibre innervation; 3) use of exercise as an intervention to prevent sarcopenia.

The Speaker: Tea Shavlakadze is a Research Associate Professor at the School of Anatomy, Physiology and Human Biology, the University of Western Australia. The research of TS has targeted factors controlling growth and maintenance of skeletal muscle mass and potential therapies for muscle disorders with a focus on in vivo studies using mouse models. Major areas of research include the role of Insulin-like Growth Factor-1 (IGF-1) in regulating skeletal muscle mass, and analyses of signalling pathways and other factors involved in many situations of skeletal muscle wasting.

Skin is the largest organ of human body. One of the major traumas to the skin is caused by burn injuries. Over a 170,000 people sustain burn injuries each year in Australia alone, of which majority are children. There are a number of possible treatments available clinically and their applicability depends on the extent of the injury. Current treatments are not only expensive but also have major limitations. Extensive work has been carried out to promote the healing process in such injuries however; the ever-arching problem of scar formation post healing is greatly overlooked. In this presentation a new tissue engineering approach will be discussed towards reduced scar wound healing. Different hybrid hydrogels and anti-scarring agents will be demonstrated as potential scaffold systems. Importance of cell motility will be highlighted along with cell proliferation to promote wound healing.

The Centre for Microscopy, Characterisation and Analysis (CMCA) provides local researchers and students in biology and biomaterials with access to infrastructure and expertise across imaging (small animal, optical, confocal, 3-D and electron microscopies), analytical (elemental, isotopic, and compound analysis) and flow cytometry (population analysis, phenotyping and sorting) platforms. With the ongoing acquisition of new bio-focussed key facilities and staff, this seminar will aim to present an overview of CMCA’s current capabilities in the biological and biomaterials space. In particular, new capabilities, research applications, plus current and future opportunities for local researchers working with bio-related samples to engage with CMCA will be presented.