What's On at UWA

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. Doctor Brian Brestovac from the School of Biomedical Sciences, Curtin University presenting on "Human papillomavirus (HPV), Cervical Intraepithelial Neoplasia (CIN) and Killer Immunoglobulin-like Receptors (KIR)". 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: By investigating the neural basis of behaviour in marine organisms, it is possible to identify the signals that govern a range of behaviours crucial for survival. In this presentation, the fields of neuroscience and ecology are integrated to explore animal behaviour and the processing of environmental signals by both the peripheral and central nervous systems of a range of (predominantly marine) organisms. Within every species’ microhabitat, the ability to detect the physical environment for setting circadian rhythms, avoiding predation, finding food and for reproductive success are often different. We use innovative neurobiological techniques such as molecular genetics, microspectrophotometry, bioimaging, electrophysiology and anatomy to trace the evolution of sensory systems and the detection thresholds for light, chemosensory signals, electric fields, water borne sound and hydrodynamic disturbances. In this way, we hope to understand how we can protect biodiversity and the varied environments each species is adapted to.

The Speaker: Professor Shaun P. Collin is a WA Premiers Research Fellow and Winthrop Professor at The University of Western Australia. He heads a large Neuroecology Group that investigates the neural basis of behaviour in both invertebrates and vertebrates, with special emphasis on sensory systems and vision. Before joining UWA from The University of Queensland, where he was a Professor within the School of Biomedical Sciences for 10 years, he spent appreciable periods of time in Canada, the United States, Germany and Australia on a range of prestigious Research Fellowships (ARC QEII, Fulbright, Alexander von Humboldt, Grass). Using a range of cutting edge techniques, his Group investigates the impacts of light on biodiversity, sustainability and health in a large diversity of animals, including humans. Prof. Collin has published over 170 scientific papers, including 2 books, and sits on the Editorial Boards of 5 international journals. He also sits on the College of Experts Panel for the Australian Research Council (ARC) and is a member of the Technology and Innovation Advisory Council (TIAC) for the WA State Government.

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 delighted to have 2 of our own students presenting final MLM and honours seminars respectively: Abdullah Ali Aseeri on 'Identification and discrimination of different strains of CA-MRSA by using MALDI-TOF MS' and Royston Ong on 'Whole exome sequencing applied to Charcot-Marie-Tooth (CMT) Disease' from the School of Pathology and Laboratory Medicine, UWA. 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 Lung Institute of WA invites you to a free seminar on: "Lung function – going global in 2012" by Professor Graham Hall from the Telethon Institute for Child Health Research. Time: 12 noon for light lunch with 12.30pm – 1.30pm presentation.

The Seminar: Compelling evidence suggests that cancer cells are generally under reactive oxygen species (ROS) stress. As mitochondria respiration is the main source of ROS generation in the cells, MnSOD is of prime importance in maintaining the tumor cellular ROS balance. It has recently been reported that generation of ROS is closely involved in PPAR ligand–induced apoptosis. However, the mechanism by which these ligands induce ROS generation remains unknown. We report the identification of human MnSOD as a PPAR target gene and that activation by PPAR agonists led to downregulation of MnSOD gene expression in vitro and in vivo xenograft model. Futhermore, histopathologic analysis of breast cancer biopsies obtained from patients treated with synthetic PPAR agonists also showed MnSOD repression. Repression of MnSOD expression was accompanied with increase in intracellular superoxide production in breast cancer cells. Suppression of MnSOD levels by small-interfering RNA or activation of PPAR in breast cancer cells increased oxidative stress and enhanced chemo-sensitivity to ROS-inducing drugs such as docetaxel and doxorubicin. Importantly, normal breast cells were completely refractory to these effects. Together, our data not only identifies MnSOD as a novel PPAR target but also provides a molecular mechanism for ROS-manipulation therapy through the intelligent use of PPAR ligands in combination with ROS-inducing drugs to preferentially kill cancer cells.

The Speaker: Dr. Alan Prem Kumar earned his Ph.D. from University of North Texas, USA. From his Ph.D. work, he discovered a novel regulatory protein, PyrR for the pyrimidine biosynthetic pathway in Pseudomonas. Because pyrimidine biosynthesis is an essential step in the progression of secondary Pseudomonas infections, PyrR presents an attractive anti-pseudomonal drug target. Dr. Kumar then pursued Postdoctoral training in Cancer Research at Sidney Kimmel Cancer Center, California, USA. He was awarded a Postdoctoral Fellowship for his work on the role of nuclear receptors in the transcriptional regulation of human myeloperoxidase, a leukocyte enzyme implicated as causative agent in atherosclerosis and Alzheimer’s disease. Dr. Kumar relocated back to Singapore to join the Faculty of Medicine, National University of Singapore as an independent Principal Investigator to continue on his expertise on nuclear receptor and cancer biology. His current research interest includes the role of nuclear receptors involved in the regulation of target genes and to elucidate mechanism and associated signal pathways. Another area of interest is to have a greater understanding of these nuclear receptors – aimed at developing newer selective PPAR gamma modulators, drugs with more potent activity and less toxicity. Towards this end, Dr Kumar identified a series of 21 structurally new PPAR gamma activators by computer-aided drug design using a combination of ligand-based and structure-based approaches. In collaboration with GenoMed, Inc, USA, he has recently identified a new tyrosine kinase involved in the progression of ovarian, breast, and prostate cancers. Inhibitors were developed against this kinase using computer-aided drug design. His goal is to use these drugs to demonstrate its effectiveness in a variety of cancer cell lines, mouse xenograft, with intent to clinical trials here in Singapore. Over the years, Dr. Kumar and his laboratory have forged relationships with scientists in cancer research and with cancer advocacy groups in Singapore.

Host: E/Prof Dharmarajan - PH) 6488 2981

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. Doctor Phil Stumbles from the School of Veterinary and Biomedical Sciences, Murdoch University presenting on "Regulating Immunity and Tolerance at Airway Mucosal Barriers". 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: The lung is a remarkable organ with gas exchange and vital immune defence roles accomplished in a branching network of airways and about 200 million alveoli. It is also an extremely dynamic tissue with rapid turnover of lung cells and their surrounding matrix which may explain the ability of new lung tissue regeneration in experimental models of lung growth. Chronic lung diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease are a major cause of illness and an enormous burden on world health systems. Treatment for these diseases is inadequate with patients unresponsive to most current therapies and, despite large programmes in drug discovery, no agents are emerging that can cure or reverse chronic lung diseases. There is hope that cell therapeutic approaches with the regeneration of new lung tissue might be achievable and initial reports using progenitor cells derived from the bone marrow suggest that this approach may ameliorate animal models of lung disease. The mechanism for this action is uncertain but likely depends on paracrine pathways rather than cell engraftment. This presentation reviews some of the milestones in pulmonary fibrosis research and presents data suggesting keratinocyte growth factor delivery in a transgene expressed by stem cells may be effective in preventing animal models of lung fibrosis.

The Speaker: Professor Laurent is currently the Head of the Research Department of Internal Medicine and the Director of the Centre for Respiratory Research at University College London. He directs a team of scientists and physicians conducting research into basic aspects of inflammation and tissue repair and has published over 200 articles in international journals of biomedical research. He was recently awarded the European Respiratory Societies Presidential Award for his contribution to lung science and is currently its head of Science. He is the Editor-in-Chief of the International Journal of Biochemistry and Cell Biology and has edited several books including a four volume Encyclopaedia of Respiratory Medicine. He is a Fellow of the Academy of Medical Sciences and Past- President of the British Association for Lung Research. In June 2012 he takes up a post at the University of Western Australia directing its newly formed Centre for Cell Therapies and Regenerative Medicine

The Three MInute Thesis (3MT) is a fun and challenging event that encourages the communication of research to a wide audience. The UWA 3MT competition finals will be held on 25th July and this presentation is a comprehensive guide to the preparation and presentation of a compelling 3MT talk. The presenter, Simon Clews,is an experienced 3MT judge who has championed the 3MT competition in Australia and internationally.

X-ray crystallography is a method of determining the arrangement of atoms within a crystal. This talk will briefly outline the technique used in the determination of crystal structures with special reference to small molecules. The instrumentation which is available to researchers at UWA for diffraction experiments will also be described. A number of results from such experiments will be presented including examples of crystal structures from the various research areas within UWA.

N-Heterocyclic carbenes (NHCs) are powerful organocatalysts for a range of chemical transformations. Our studies have been underpinned by new approaches to acyl azolium intermediates and have allowed a number of novel catalytic reactions to be developed. In this presentation studies on the use of NHCs to catalyse sigmatropic rearrangements, (4 + 2) annulations, and cascade Brønsted/Lewis base mediated reactions, will be presented. The application of these reactions to the total synthesis of 7 deoxyloganin will be presented.

The primary transcripts must then undergo extensive processing, including the maturation of 5’ and 3’ termini, RNA-editing and the splicing of many group-II-type introns (the precise number varying by species), which lie mainly within complex I subunits but also disrupt the coding-regions of several genes encoding ribosomal proteins. The splicing of these introns is therefore essential for the expression of the coding sequences they interrupt, and thus for respiratory activity. Yet, despite the importance of proteins that influence mitochondrial gene-expression, functions have been established for only a handful of such proteins in plants. In non-plant systems, the splicing of group-II introns is facilitated by proteins encoded within the introns themselves (Maturases, Mat’s). Yet, the plant mitochondrial introns are degenerated and also lost their intron-encoded ORF. It is thus anticipated that their splicing in the organelles requires the participation of nuclear gene products. In addition, the roles of nuclear-encoded factors in mitochondrial RNA-metabolism may provide means to link organellar gene expression and function to other cellular responses to energy state, environmental stimuli, and/or developmental cues. However, the precise functions still remain largely unknown for many of these proteins in plant mitochondria. By using biochemical and genetic approaches we established the roles of different proteins in the splicing of many of the mitochondrial introns in plants. These are diverse in origin and presumably in mechanism. Defects in interactions between this class of proteins and their RNA partners have been linked to growth and developmental defects, which include reduced germination, retarded growth phenotypes and cytoplasmic male sterility.

LIWA invites you to a free seminar on: "eResearch and the opportunities of applying digital technology in healthcare research" by Professor Jennifer Harrison from iVEC@UWA. Time: 12 noon for light lunch with 12.30pm – 1.30pm presentation

Come and hear prominent UWA, national and international speakers give varied and fascinating insights into Innovative Discoveries in Science through Advanced Mass Spectrometry. A full list of speakers and seminar titles is available on request to [email protected]

You are invited to attend this live demonstration of the new Hirox KH-8700. This will be an overview of the system and demonstration including the 3D rotary lenses, multifocal functions and a variety of unique lenses and adaptors. All are welcome to attend.

Analyses of shipwreck artefacts are essential in order to gain information about the chemical nature of materials, provenance, state of deterioration and even technological information about formation processes. For more than 20 years, conservation scientists from the WA Museum and UWA staff have collaborated to resolve many such issues, particularly those associated with organic archaeological materials. Solution NMR spectroscopy, for example, has been used to identify pitches, resins and tars, to gain information about the precursors to these materials and to reveal information about the heating regimes that they were subjected to in their preparation while solid state NMR spectroscopy has been used to determine the deterioration of waterlogged wood and ivory and to identify chemical processes that have occurred after their conservation treatment. Dr Godfrey’s illustrated presentation will highlight archaeological, conservation and analytical aspects of work undertaken on a variety of objects from local and international shipwrecks

We hypothesize that the massive changes in C4/C3 related gene expression are controlled by a subset of transcriptional regulators, which are essential for C4 photosynthesis establishment and/or maintenance. We analyze the Cleome genus, which includes closely related C4 (Cleome gynandra) and C3 (Cleome hassleriana) species and exhibits phylogenetic proximity to the model species Arabidopsis thaliana.In order to elucidate the regulatory network behind the C4 syndrome in Cleome we are employing two strategies: (i) A single candidate gene approach derived from a global comparative analysis of transcriptome data sets of C4/C3 species (including Cleome hassleriana and gynandra) generated by 454 and Solexa sequencing, which targets will be further described biochemically and genetically (e.g. via over-expressor and knock-out lines in Arabidopsis thaliana) and (ii) co-expression analysis for the identification of the regulatory modules which will include a developmental gradient of photosynthetic and a subset of non-photosynthetic tissues.

Protein molecular motors are natural nano-machines that convert the chemical energy obtained from the hydrolysis of adenosine triphosphate (ATP) into mechanical work which is central to cellular motion, muscle contraction, cell division and a multitude of other critical biological processes. Remarkably, protein molecular motors differ fundamentally from artificial devices in that the conversion from chemical energy to mechanical energy is done directly, rather than via an intermediary state as in e.g., heat for thermal engines. This fundamental difference results in a far better efficiency (close to 100%, for both linear and rotary motors) of these natural mechanical devices compared to artificial ones. This exceptional efficiency, together with the small scale of protein molecular motors, has prompted an increasing number of studies focused on their integration in hybrid micro- and nanodevices. However, and despite tremendous progress in the engineering of molecular motors, much needs to be learnt from Nature, in particular regarding the cooperative behaviour of molecular motors in vivo, before coming even close to efficiency in in vitro devices.

Filamentous fungi are very successful in colonizing micro-confined maze-like networks (e.g., soil, wood, leaf litter, plant and animal tissues), suggesting that they may be efficient solving agents of geometrical problems. The growth behaviour and optimality of space-searching algorithms of several fungal species has been tested in microfluidic mazes and networks. First, it was found that the growth behaviour of all species was strongly modulated by the geometry of micro-confinement. Second, the fungi used a complex growth and space-searching strategy comprising two algorithmic subsets: (i) long-range directional memory of individual hyphae and (ii) inducement of branching by physical obstruction. Third, stochastic simulations using experimentally measured parameters showed that this strategy maximizes both survival and biomass homogeneity in micro-confined networks, producing optimal results only when both algorithms are synergistically

Organic dyes with a charge-resonant electronic structure (for example, Michler’s Hydrol Blue, below) are venerable molecules, having played a critical role in the development of the synthetic chemical industry. More recently, they have attracted attention because the environmental sensitivity of their optical response makes the useful as molecular sensors and markers. The fluorescence quantum yield of dyes can be modulated over six orders of magnitude in different environments. Large variations in the nonlinear optical response are also observed. In my talk, I will discuss the chemical and physical concepts underlying the notion of charge-resonance, and describe its mathematical formulation. I will show explicitly that relatively simple 2- and 3- state models based on these concepts can be used to understand and even predict the results of quite complicated and high-level computational quantum chemistry calculations. I will show that models based on the concept of resonating charge forms, which were originally designed to model the color of dye molecules, can also be applied to understand apparently unrelated properties e.g. their nonlinear optical response and also their nonradiative decay behavior. These properties are important to understanding the use of these dyes in several very recent applications, which I will also discuss.

Urukthaplestatin A (Ustat A) is a novel natural product, consisting of oxazoles and thiazoles inbedded in a macrocycle. It has extraordinary cytotoxicity against cancer cells in the desirable low nanomolar range (average GI50 = 5.6nM). It does not share structural homology with other classes of marketed cancer therapeutics, and it has a different activity profile to compounds with structural similarities indicating a possible novel and unique mechanism of action. We use novel, modular oxazole methodology that generates numerous Ustat A analogs, and specifically we have designed compounds that will explore its structure-activity relationship and mechanism of action. Given the cytotoxicity and the novelty of these molecules, they are ideal starting points for developing new cancer therapies.

Molinski and co-workers discovered Sanguinamide B (San B) from a single species of nudibranch. The San B natural product contains two thiazoles and one oxazole, and is a modified octapeptide macrocycle; unlike other natural products isolated from this sponge, San B contains two proline residues, where these two residues are control the conformation of the macrocycle. The potent cytotoxic and antibiotic properties of other macrolides isolated from this nudibranch species, and the small microgram quantities of the compound that are available from the natural source, make this natural product a very attractive compound to synthesize. We have synthesized and tested San B and numerous analogues against gram +ve, gram –ve bacteria as well as against mammalian cancer cell lines. Not surprisingly, the conformation of these compounds dictates their biological activity.

"Our research focuses upon how the virulent bacterial phytopathogen Pseudomonas syringae establishes disease in the model plant Arabidopsis thaliana. P. syringae delivers a suite of ~ 30 effector proteins into the plant cell." Detailed abstract available [email protected]