SCHOOL OF ANATOMY & HUMAN BIOLOGY
SEMINARS
Semester Two 2009

Room 1.81, Anatomy & Human Biology Building

The University of Western Australia    (off Hackett Entrance No. 2)

Peter Arthur, Biochemistry and Molecular Biology, UWA

Oxidative stress in tissue: What is it and how do you measure it?

The Seminar:

Oxidative stress is caused by reactive oxygen species (ROS), also known as free radicals, and is evident in many chronic diseases and conditions.  Although well recognized as harmful to human health, developing a successful therapy against oxidative stress has proven to be very challenging.  I believe this failure is a reflection of our poor understanding of the complex interactions between ROS, tissues and the use of non-specific antioxidants.  We are using multiple analytical techniques to improve our understanding of oxidative stress in muscle tissue from a mouse model of muscular dystrophy.  I will discuss some of the challenges we are encountering.

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Dr Michael Edel, Centro de Medicina Regeneration de Barcelona

Reprogramming of somatic cells to induced pluripotent stem cells (IPS) for Clinical and Basic Research

The Speaker:
Dr. Michael Edel completed his BSc with honours in Anatomy at the University of Western Australia and a PhD in Pathology in 1999 from the same University. He has worked at many world-leading Research centres such as The Australian National University, John Curtin School of Medicine; the Institute Marie Curie in Paris, France; the Netherlands Cancer Institute in Amsterdam and the Centre of Genomic Regulation in Barcelona. Currently he is a Carlos III Investigator from the Centre of Regenerative Medicine in Barcelona, Spain. His research interests are angiogenesis, in which he has a scientific patent for the role of a new gene in tumour angiogenesis, cell cycle of mammalian cells resulting in two major publications in Cell and Oncogene, and in human pluripotent stem cells, particularly the clinical and basic research of induced pluripotent stem cells (iPS cells). This work has resulted in a publication that is part of a body of work that was voted breakthrough of the year by Science in 2008.

The Seminar:
The discovery less than three years ago that a set of defined factors, Oct4, Sox2, Klf4 and cMyc can reprogram human fibroblasts into induced pluripotent stem cells (iPS cells) has opened a up huge potential for treatment and research of human disease, effectively by-passing ethics issues and immune rejection issues of stem cell therapy. Since then the field has moved rapidly enabling new methods to make iPS cells faster, safer and more efficient. To date, a number of “proof of principle” studies have demonstrated the use of iPS cells to treat a number of diseases such as sickle cell anemia, fanconi anemia, amyotrophic lateral sclerosis (ALS), and Parkinson’s. A number of “bottlenecks” still must be addressed before iPS technology can be of clinical use, such as well-defined clinical-grade differentiation protocols and the induction of cancer. This seminar will discuss our current “proof of principle” study to use iPS technology to treat spinal cord injury and insights into the mechanisms of iPS formation.

Associate Professor Silvana Gaudieri, School of Anatomy & Human Biology, UWA

‘Hepatitis C adaptation to the immune response: relevance to infection and therapy outcome’

The Seminar:
Recent advances in molecular virology have led to the development of novel small anti-HCV drugs that target specific viral proteins integral to the HCV life cycle. Preliminary studies using these agents have revealed a number of drug-resistance mutations within the target HCV proteins. We, and others, have previously demonstrated the influence of the host’s immune response on viral diversity at both the individual and population level and identified sites within the HCV genome that are under immune pressure. In this study, the frequency of pre-existing drug resistance mutations within a drug-naïve population is determined and the potential for drug and immune selective pressures to intersect at sites along the HCV genome is explored.

The Speaker:
Associate Professor Gaudieri is a UWA graduate who completed her PhD in 1996 in the area of immunogenetics.  She continued her research in Japan and the UK and returned to UWA in 2003. Her current research examines host-viral interactions and how this relationship can influence infection and therapy outcome.

Dr Jeremy Shaw, UWA Centre for Microscopy

Cryo-preparation of tissue for ultrastructural characterisation: New opportunities in biological electron microscopy

The Speaker:
Dr Jeremy Shaw is a research associate with a Ph.D. in marine and biological sciences. His principal research interests involve the elucidation of the cellular and organic matrix driven processes of invertebrate biomineralisation. Dr Shaw’s main field of expertise is in electron microscopy (TEM and SEM), coupled with analytical techniques such as energy-filtered TEM and X-ray microanalysis (EDS). He is also responsible for coordinating research involving the CMCA’s new cryo-preparation facility, which includes a state of the art high-pressure freezer, freeze-substitution and cryo-microtomy system.

The Seminar:
The cryo-facility at the Centre for Microscopy, Characterisation and Analysis comprises a suite of state-of-the-art instrumentation for preserving cells and tissues for electron microscopic investigations. Cryo-fixation of biological material offers a number of significant advantages compared to conventional chemical methods of tissue preservation. In particular, cryo-fixation results in the immediate cessation of biological activity down to the atomic level, thereby immobilising and preserving all cellular constituents. As a result, the ultrastructure of tissues is often free from distortions and the samples elemental and antigenic characteristics are retained. These methods of sample preparation are particularly complementary to immunological studies where the retention of antigenicity is required.

Postgraduate - "Rites of Passage" - Seminar

Lloyd White, Deakin University

Characterisation of Caspase-14 in Human Trophoblast Differentiation

The Seminar:
The placenta forms a barrier regulating the transfer of gases, nutrients and wastes between the mother and the developing conceptus, through a process of differentiation of trophoblast cells. Disruption to the function or differentiation of the human trophoblast may result in preeclampsia, a maternally manifested disorder of pregnancy characterised by hypertension and proteinurea. Caspase-14 is an unusual caspase in that it is not involved in apoptosis. Furthermore, it possesses a limited distribution predominantly related to barrier forming tissues. In the epidermis, caspase-14 is expressed in the apical differentiating layers, where it cleaves profilaggrin to stabilise intracellular keratin intermediate filaments, and indirectly provides natural hydration and UV protection to the corneocytes. Thus, caspase-14 is vital to the maintenance of the barrier function of the skin. In light of its function in keratinocyte differentiation and barrier formation, it is hypothesised that caspase-14 possesses a conserved function in the human trophoblast. To examine this, first trimester, term and preeclamptic human placenta samples were probed for several differentiation-associated genes; while the intricate pathways were dissected via the manipulation of the cytotrophoblast-like BeWo cell line to undergo differentiation, and RNA Interference to elucidate the role of caspase-14 during BeWo differentiation. Gene and protein expression were predominantly analysed by Real Time PCR and Western Blot analysis. The obtained data will be presented and theories put forward as to the function of caspase-14 in the human trophoblast.

The Speaker:
Having started life an infant, then growing up in the untamed wilds of the South West of Western Australia Lloyd moved to Perth in 2000 to start a Bachelor of Science at the University of Western Australia. Four years later he emerged into the sunlight of the real world, before quickly scurrying back to the relative comfort of academia to pursue his Honours in the skeletal muscle laboratory of Prof. Miranda Grounds and Dr. Jason White. After gaining a 1st Class Honours Lloyd aborted an attempt to pursue work in Melbourne to take up a PhD position studying the function of caspase-14 in the human placenta with Prof. Dharmarajan and Dr. Charles in Anatomy and Human Biology at The University of Western Australia. He submitted his PhD thesis in September 2008 before finally migrating to Melbourne in January 2009 and, having run the gauntlet of the global financial crisis, finally managed to find himself postdoctoral research position in the skeletal muscle atrophy laboratory of Dr. Aaron Russell at Deakin University.

Professor Terri-Ann White, Director, UWA Publishing and Institute of Advanced Studies

University publishing houses in an age of scarcity

Terri-ann White is Director of the Institute of Advanced Studies (since 1999) and UWA Publishing (since 2006). UWA Publishing has recently undergone a renewal, with a new name and image and a set of initiatives to become more visible in academic and general publishing.

She will  talk about some of the ways that academic publishing is shifting and developing in an era where we might find new ways to use resources more carefully.

Professor Emeritus Henning Schneider, University of Berne, Switzerland

Tolerance of Human Placental Tissue to Severe Hypoxia and its Relevance for Dual Ex Vivo Perfusion

The Speaker: Following retirement from his academic position and as director of the Maternity Hospital at the Insel Spital in Berne he has remained active in the field of placental research. This activity is based on several international collaborations, which had developed over several years with the Departments of Pharmacology (Dr. Karen May and Prof. Siegmund) and Obstetrics and Gynecology (Prof. Zygmunt) at the University of Greifswald in Germany, the Division of Infectious diseases at the Case Western Reserve University Medical Center in Cleveland, US (Prof. Christoph King), the Department of Obstetrics an Gynecology at the University of Lund in Sweden (Proff. S. Hansson and K. Marsel), the Department of Obstetrics at the Maternity Hospital at the University of Marburg in Germany (Prof. S. Schmidt), the Department of Obstetrics and Gynecology at Yale University in New Haven, US (Seth Guller, PhD).

The Seminar: In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20–30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus without undergoing severe damage.

There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia.

Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the artificial reperfusion, may lead to further improvement of the ex vivo perfusion technique.

CANCELLED

Paul McMenamin, Holly Chinnery, Nina Vagaja, Martin Zinkernagel, Sam McLenachan, Ocular Immunology Group, School of Anatomy & Human Biology UWA, Centre for Ophthalmology and Visual Sciences.

Recent advances in basic research in immunological mediated diseases affecting the eye: from the cornea to the retina.

Prof Alan Harvey, School of Anatomy & Human Biology, UWA 

Music, evolution and 'Homo sapientior'

The Speaker: Alan Harvey was educated at the University of Cambridge before undertaking a PhD at the Australian National University. After working in the USA and at Flinders University he moved to The University of Western Australia in 1984. He is currently Professor and Deputy Head of the School of Anatomy and Human Biology. His main experimental laboratory interests are in neurotrauma, neurodegeneration and neurotherapy, the research primarily focused on the visual system. He is testing a range of approaches including gene therapy and cell transplantation in an effort to enhance cell survival and regeneration after injury.  He is also, however, passionate about music and over the past 35 years or so he has sung in choirs and played many concerts as a solo artist or as a member of various folk or rock bands.  He has the long-term ambition of bringing his neuroscience and musical interests together, intending (still!!) to write a book about the role of music in human evolution and modern-day society.

The Seminar: In this presentation, Alan will consider why music is a universal attribute and ask what, if any, evolutionary significance it had. Why do we have this communication system side-by-side with language, and is music still relevant to the welfare of our species today? In suggesting answers to these intriguing questions, he will take you on a wide-ranging journey encompassing anthropology and archaeology, genetics, neuroscience and behaviour, brain imaging, and modern day neurotherapies. He argues that music (and with it dance) promotes the collective expression and experience of emotions and fosters social cohesion, of critical importance to our early ancestors and still important to our sense of mental well-being today.

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Semester One Seminars

Dr Judy Anderson, University of Manitoba Winnipeg, Canada 

Old and new drugs with anti-fibrosis and growth-promoting effects in dystrophy and aging

Abstract:
The growth of skeletal muscle and its regeneration from disease or injury require activation of stem cells to form new muscle. This process is also coordinated with regeneration of non-contractile tissues such as connective and vascular tissues. Recent research has determined that halofuginone is an effective anti-fibrotic drug that has very strong potential to benefit conditions where muscle fibrosis is secondary to disease or injury, and may interfere with functional recovery of muscle during regenerative myogenesis. MyoNovin is a new drug that was formulated based on our work on nitric oxide-mediation of stem cell activation. It directs nitric oxide to skeletal muscle, activates satellite cells, and increases the potential for coordinated regeneration and for muscle growth or its resistance to age-related atrophy. Both approaches could benefit treatment of muscular dystrophy.

Biography:
Dr. Judy Anderson (PhD 1985) was trained as an anatomist, and was a Professor of Human Anatomy and Cell Science in the Faculty of Medicine at the University of Manitoba in Winnipeg, Canada from 1988-2007.

Judy does basic and biomedical research using cell imaging, molecular biology and physiology approaches, and also conducts research on human rehabilitation assessment protocols and interprofessional education.  Judy is currently Professor and Head of the Department of Biological Sciences at the University of Manitoba (janders@ms.umanitoba.ca).

9 February at 1:00pm

Professor Dr Rupert Hallmann, Institute for Physiological Chemistry Munster University

The Endothelial Glycocalyx and its Role in Leukocyte Extravasation

The Seminar:
The glycocalyx of the cell surface influences the interaction of cells with their environment. The interaction of leukocytes with blood vessel endothelium is central for the onset and intensity of an inflammatory process. This seminar will discuss our current concept of the role of the endothelial cell surface glycocalyx, its changes in activated endothelium as well as its possible role in modulating the adhesion and the transmigration of leukocytes in inflammation.

The Speaker:
Professor Hallmann is currently based at the Wesfaelische Wilhelms-Universitaet, in Muenster, Germany and was previously at Lund University, Sweden, and Max-Planck Society, Erlangen, Germany, after graduating from the Max-Planck-Institute for Development Biology, Germany. His central research interests are: The Role of the Blood Vessel Endothelium in Inflammation and Extravasation; Mechanisms of Endothelial Cell Angiogenesis & Differentiation and Mechanisms of Endothelial Cell Activitation. He has 46 publications, 40 of these peer-reviewed and 6 monogrophies.

Associate Professor Mahendran Mahadevan, Departments of Obstetrics and Gynecology University of Arkansas for Medical Sciences Little Rock, Arkansas, USA.

Prostate cancer gene immunotherapy and stem cells

The Seminar:
Prostate cancer (PC) is the most prevalent male cancers.  PC is a good target for immunotherapy because prostate is not an essential organ.  Recombinant adeno-associated virus type 2 (AAV) vectors are useful for gene-loading of Dendtritic cells (DC and for the rapid generation of cytotoxic T lymphocytes (CTL) against self antigens such as prostate specific antigen (PSA) and  prostate specific membrane antigen (PSMA) genes. In this study, we have carried out comparison of protein pulsing of DC and AAV-loading of PSA. In collaboration with Dr. Hermonat, we characterized the DCs and CTLs to investigate immunobiology mechanisms.  Also, CTL killing of PSA or PSMA positive cells were demonstrated.  An effective protocol for targeting self antigen PSA or PSMA was developed.  AAV-PSA antigen gene delivery in to DC is superior to protein loading in terms of CTL killing ability against PSA positive cells. Upregulation of co-stimulatory molecule CD80 may be partly the reason why our protocol is highly effective.  The efficient protocol developed may be used as immunotherapy for PC.  Preliminary clinical studies of adoptive CTL treatment against PC in China are encouraging. Current standard treatments include surgery, hormone therapy, radiation therapy and chemotherapy or combination of them but 50% of patients with the metastasis still die. Therefore, early diagnosis and new treatments such as experimental  immunotherapy, geneimmunotherapy and  stem cell therapy are urgently needed.  Recently, stem cells and stem cell like cells are implicated in tumor formation, progression and metastasis.  Also, Dr. Higuchi’s group has proposed tumor progression and epithelial-mesenchymal transition (EMT) during the mtDNA depletion in PC cell lines. EMT and decrease in mtDNA also occurs during early embryonic development.  In collaboration with Dr. Higuchi, we plan to study the role of stem cells, mitochondria and mtDNA during EMT in embryonic development and epithelial cancers such as PC, bladder, breast, cervical, uterine and ovarian cancers.  Information gained will be useful in prevention of cancer formation, control of cancer progression and early diagnosis of cancers.

The Speaker:
 “Dr. Mahadevan obtained his Veterinary Medicine in Sri Lanka and  PhD in reproductive biology at Monash University, Melbourne.  He has been involved in human sperm/embryo banking and human in vitro fertilization for 30 years. He is an Associate Professor in Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences.  He is  a  Co-course director for medical genetics and Co-Chair of Institutional Research Board.  He is currently responsible for a University placental/cord blood tissue bank for research purposes.  His current research interest includes prostate cancer stem cell biology, cryobiology of cord blood stem cells and stem cell therapy”.

Professor Nadia Rosenthal, EMBL-Monterotondo Outstation. Rome Imperial College London  Australian Regenerative Medicine Institute, Melbourne

Macrophages to the rescue in muscle regeneration

The Seminar:
The resolution of tissue injury involves a complex interaction between local repair mechanisms and cells of the immune system, which participate in the removal of necrotic cells but may also provide support for the action of stem and progenitor cells in the repair process. Macrophages are the major infiltrating cell population in injured skeletal muscle, required for removal of damaged myofibers as well as for subsequent muscle regrowth and differentiation. In a mouse model of enhanced regeneration of skeletal muscle expressing a local IGF-1 isoform, we found that that improved bone marrow contribution to rebuilding damaged muscle could be attributed to the myeloid/macrophage lineage. To test whether this requires the local polarization of macrophages towards an anti-inflammatory, or M2 phenotype, we exploited a genetic blockade to the induction of C/EBPb transcription factor in response to injury, which is essential for macrophage polarization.  Persistence of inflammatory M1 macrophages in damaged muscle of these mice was insufficient for effective regeneration, which was impaired in the absence of M2 polarization. These observations highlight the role of infiltrating immune cells in tissue repair and provide the first direct genetic link between the action of M2 macrophage polarisation and muscle regeneration.

The Speaker:
Nadia Rosenthal heads the European Molecular Biology Laboratory Outstation in Monterotondo, Rome, holds a Professorship in Cardiovascular Science at Imperial College London, and is Founding Director of the Australian Regenerative Medicine Institute at Monash University Melbourne. Her research focuses on developmental genetics, the molecular biology of ageing and the role of stem cells in tissue regeneration. She delivered the 2006 Howard Hughes Holiday Lectures on Potent Biology: Stem Cells, Cloning and Regeneration. She co-edited the definitive text Heart Development, served on the editorial staff at the New England Journal of Medicine, holds EMBO membership and is an Australia Fellow.

POSTPONED

Professor Nagini Siddavaram, Department of Biochemistry & Biotechnology Faculty of Science Annamalai University, India

Of humans and hamsters: The hamster buccal pouch carcinogenesis model as a paradigm for oral oncogenesis and chemointervention

The Seminar:
Animal tumor models that closely mimic human oral cancers are paramount in elucidating the mechanisms of neoplastic transformation besides providing leads to effective chemoprevention. The hamster buccal pouch (HBP) carcinogenesis model is one of the most well characterized systems for analyzing the development of oral squamous cell carcinoma (OSCC) a major cause of mortality and morbidity worldwide. HBP carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA), reiterate many of the features observed in human OSCCs. The major risk factors associated with human oral cancer such as tobacco, betel quid and alcohol promote HBP carcinogenesis. SCCs induced by DMBA in the cheek pouch of Syrian hamsters are morphologically and histologically similar to human OSCC. Like human oral carcinogenesis, HBP carcinogenesis is a multistep process that involves sequential progression from hyperplasia to invasive carcinoma through varying degrees of dysplasia. In addition, HBP tumours express several biochemical and molecular markers that are also expressed in human OSCC. Multiple signaling pathways are dysfunctional in both human and hamster OSCCs. In particular, cell proliferation, apoptosis and angiogenesis are intricately interlinked in malignant transformation of the HBP mucosa by DMBA. The HBP carcinogenesis model is ideal for testing putative chemopreventive and chemotherapeutic agents because of easy accessibility for examination, and follow-up of lesions. Chemoprevention studies in the HBP model can serve as a crucial link in the potential efficacy assessment of candidate agents for oral cancer prevention and therapy. 

The Speaker:
Professor Siddavaram’s field of research is cancer biology. Her current research interests include comparative oncology, cancer chemoprevention and apoptosis.  She has completed research projects for DST and UGC, Mitsui Norin Co., Japan and has an ongoing major DST research project. She has published 4 books and 135 research papers. Her awards and honours include: Commonwealth Award for University Teachers for postdoctoral research at the Molecular Oncology Group, University of Liverpool, the National Young Woman Bioscientist Award, Department of Biotechnology (DBT), Government of India and the Best Researcher Award Annamalai University.

Associate Professor Luis Filgueira, School of Anatomy & Human Biology, The University of Western Australia

Bio-corrosion of metal implants and effects on immune cells

The Seminar:
Metal-containing biomedical implants are prone to bio-corrosion, affecting the host in up to 20% of cases with serious side effects. However, little is known about the process of bio-corrosion and the effects of the resulting metal ions (aluminium, chromium, cobalt, manganese, molybdenum, titanium and vanadium) on the organism, especially in the context of orthopaedic implants. This seminar will present new results about the role of osteoclasts (bone resorbing cells) in the process of bio-corrosion of metal implants and about the effects of various metal ions on immune cells.

The Speaker:
Luis Filgueira graduated in 1985 (doctorate in 1987) in human medicine at the University of Basel, Switzerland.  He did several years of internship as clinical and research fellow at different hospitals in Switzerland, to be trained as a surgeon. Because of his love to basic science and teaching, he moved into teaching and research in 1994, to become a senior teaching and research fellow in anatomy at the University of Zurich.  After Habilitation in the area of Immunology in 2001 at the University of Zurich, Luis moved to Australia and accepted the present appointment.
Luis’ research interests are in cellular immunology and bone research, using a variety of morphological, cellular and molecular methods and addressing basic, but clinically relevant questions. At UWA, Luis has done substantial research in the area of metals in biology, focussing on side effects of orthopaedic implants on immune functions.

Mr Oron Catts, SymbioticA, School of Anatomy & Human Biology, The University of Western Australia

The works of SymbioticA and new directions

In 2008 SymbioticA in a jointly funded initiative between The University of Western Australia and the Western Australian Department of Culture and the Arts became a Centre of Excellence in Biological Arts at UWA. The success and growth of this research lab as a CoE within the School of Anatomy and Human Biology reflects the burgeoning area of artists engaging with biological sciences internationally, with similar organisations emerging in Portugal, Netherlands, USA and beyond.

SymbioticA Director, Oron Catts will discuss the new directions and activities that SymbioticA is involved in: including the field laboratories being set up in locales near Mandurah, collaborations being established with engineering and water research, ARC linkage grant to architecture at RMIT; future exchanges with the Royal College of Art London and a SymbioticA/Arts Catalyst Synthetic Biology Workshop with the Imperial College London and National Centre for Biological Sciences Bangalore India.  

Professor Charles Watson,  Division of Health Sciences, Curtin University of Technology

Genetic neuroanatomy of the hind brain and spinal cord

Dr Marc Ruitenberg,  School of Anatomy & Human Biology, The University of Western Australia

Being an olfactory receptor neuron: a story of life and death

The Seminar:
The olfactory pathway, which allows us to smell, is incredibly plastic and a site of sustained adult neurogenesis (i.e.
birth of new neurons). Neurogenesis in the nasal neuroepithelium occurs to replace other neurons that have died. Adult-born epithelial neurons can successfully regrow an axon into their central nervous system and restore appropriate connectivity. Because of unsurpassed regenerative potential, the olfactory pathway offers an attractive model to study various aspects of nerve cell injury and regeneration. Research on the role of macrophages during epithelial regeneration will be presented with special emphasis on the chemokine receptor CX3CR1. The data indicate that signalling through the CX3CR1 receptor provides a neuroprotective environment that additionally allows for neuronal replacement from endogenous stem/progenitor cells. Together, the results contribute to a deeper understanding of the cellular and molecular parameters that drive the process of neuroregeneration.

The Speaker:
Marc Ruitenberg completed an undergraduate degree in Biochemistry in 1997 after which he commenced his doctoral studies in the Laboratory for Neuroregeneration, headed by Prof. Joost Verhaagen, at the Netherlands Institute for Neuroscience. He was awarded a PhD degree in Molecular Neuroscience from the Free University Amsterdam (The
Netherlands) in May 2003. Marc joined the School of Anatomy & Human Biology in June 2003. His main research interests are in the areas of nervous system injury, plasticity and regeneration.

5th May at 1.00pm

Dr Thea Shavlakadze, School of Anatomy & Human Biology, The University of Western Australia 

Making muscles big and small: focus on interactions between IGF and TNF

The Seminar:
Skeletal muscle, which constitutes about 40% of the mass of the human body, is specialized contractile tissue that moves all parts of the skeleton and is essential for breathing; skeletal muscle is also important as a source of heat generation and as a regulator of metabolism. In humans, increasing the performance, strength and mass (hypertrophy) of skeletal muscle is of central interest to the science of sports medicine, and adequate skeletal muscle function is fundamental for normal healthy independent living. Extreme loss of skeletal muscle mass and function occurs in disuse atrophy, situations of inflammation (cachexia), chronic heart failure and diseases like muscular dystrophy. Normal ageing is also associated with decreased muscle mass and strength.
What factors regulate skeletal muscle mass and what mechanisms protect against muscle atrophy? Insulin-like growth factor-1 (IGF-1) is an anabolic cytokine that impacts the maintenance of skeletal muscle mass and is closely associated with muscle. On the other hand, inflammation and particularly the pro-inflammatory cytokine tumour necrosis factor (TNF) is implicated in the loss of skeletal muscle mass. The seminar will focus on the mechanisms of skeletal muscle atrophy and hypertrophy influenced by IGF-1 and TNF and the signalling pathways involved in the gain and loss of muscle protein content.  

The Speaker:
Thea Shavlakadze obtained a PhD in September 2005 from the School of Anatomy & Human Biology, UWA. Her PhD project, entitled Skeletal muscle remodelling in transgenic mice with skeletal muscle specific over-expression of insulin-like growth factor-1 studied the roles of IGF-1 in skeletal muscle in vivo. Since 2005 she has conducted her research at UWA. She is currently a chief investigator on 3 NH&MRC grants and has established numerous international and national collaborations. Her current research includes factors controlling muscle wasting with respect to ageing and the role of oxidative stress.

Professor Eric Meslin, Director, Indiana University Center for Bioethics

Bioethics and the Body: Experimentation, Education,and Exhibition

Professor Eric M Meslin is Director of the Indiana University Center for Bioethics, Associate Dean for Bioethics and Professor of Medicine, and of Medical and Molecular Genetics in the Indiana University School of Medicine. He is also Professor of Philosophy in the School of Liberal Arts, Co-Director of the IUPUI Signature Center Consortium on Health Policy, Law and Bioethics and 2009 IAS Professor-at-Large.

He came to Indiana University in July 2001 from the National Bioethics Advisory Commission (NBAC), where he had been Executive Director since 1998. NBAC was appointed by President Bill Clinton to advise the White House and the federal government on a range of bioethics issues including cloning, stem cell research, international clinical trials, and genetics studies.

A Canadian by birth, Professor Meslin received his B.A. in Philosophy from York University and both his M.A. and Ph.D. from the Bioethics Program in Philosophy at the Kennedy Institute of Ethics at Georgetown University. He has held academic positions at the University of Toronto and at the University of Oxford and is currently Visiting Professor-at-Large at the University of Western Australia.

He has more than 80 publications on topics ranging from international health research to science policy, including Belmont Revisited: Ethical Principles for Research with Human Subjects co-edited with James F Childress and Harold T Shapiro.

He has been a consultant to the World Health Organization, the US Observer Mission to UNESCO, the Canadian Institutes of Health Research and sits on several boards and committees including the Stem Cell Oversight Committee of the Juvenile Diabetes Research Foundation, the Indiana Organ Procurement Organization and the Board of Directors of Genome Canada. In 2008 he was appointed a Chevalier de L’Order Nationale du Mérite (Knight of the National Order of Merit) by the Republic of France.

Dr Lekha DineshKumar, Centre for Cell and Molecular Biology (CCMB), Hyderabad, India

Role of tyrosine kinase Ephb4 in the wnt pathway and its significance in the development of colon cancer

Colorectal cancer almost invariably initiates with an activation mutation in the wnt signalling pathway, the single most dominant force in controlling cell fate along the crypt-villus axis in the small intestine. This process results in the up regulation of various intermediates in the pathway, especially Receptor Tyrosine Kinases (RTK’s). Microarray experiments revealed upregulation of Ephs, (a major class of RTK’s), especially Ephb4, in Apc flx/flx models. Hence we determined the role of EphB4 in the wnt pathway in combination with several wnt pathway mutant regulators. It has shown to be an inducer of the pathway and its knockdown by corresponding shRNA and siRNAs brought down the pathway effectively. Human colorectal cancer tissues showed varying levels of Ephb4 depending on the different clinical stages and grades of tumours. Hence EphB4 could be used as a wnt based assay system in the early diagnosis of colon cancer. The role of EphB4 in the development and progression of early lesions in the mouse intestine is being investigated by over expressing and misexpressing EphB4 cDNA in the mouse transgenics. This would help us to understand the importance of this particular tyrosine kinase in the development and progression of cancer

Another project of interest in my lab is to look at the role of microRNAs (oncomiRs) in the development of colon and breast cancer. OncomiRs, a special class of non-coding microRNAs are found to be associated with a large number of cancers. Consequently impaired miRNA expression is implicated in various tumours. We adopted a multidisciplinary approach consisting of in silico, in vitro and in vivo studies for identifying deregulated microRNAs and their targets. Since wnt pathway is found to be deregulated in both colon as well as mammary tumours, the miRNAs harbouring the wnt pathway genes are of significance in both malignancies. This would also open the possibility of using these small RNA molecules for the prognosis, diagnosis and treatment of cancer in future. MicroRNA profiling in human breast cancer samples identified specific class of microRNAs which are deregulated in these cancers. A state of art transgenic strategy with an aim to silence, over express and misexpress these miRNAs implicated in the wnt pathway and thereby breast cancers would help us to create in vivo disease models which would eventually identify previously unappreciated tumour supressors and oncogenes and also address many questions about the origin, development and progression of these diseases.

Associate Professor Neville Bruce and Dr Steve Johnson, Centre for Integrated Human Studies: School of Anatomy & Human Biology, The University of Western Australia

Education for world futures:  a role for Integrated Human Studies in online global learning

The Seminar
We live in a time of unprecedented growth of science and technology with consequent escalating rates of material and social change. Global warming, war, terrorism, the nuclear arsenal, population and information explosions, extreme poverty and affluence, resource depletion and pollution, advanced bionics and genetic engineering  will all impact on what it means to be human in the 21st century and well beyond. This is the world our students will inherit: this is the challenge university education must meet.
Education for World Futures directly addresses this challenge.  Two, fully online or blended teaching foundation units: Humanity in the 21st Century and Human Action for Global Futures will be established in 2009.   These units bring together the sciences, social sciences, arts and humanities to study the nature and future of humankind. They will provide students with an understanding of their biological and cultural origins, their history and social organisations, their reliance on and interaction with the “natural world” and the skills required to make a meaningful contribution to human wellbeing in a sustainable world environment.
Plans for these units have been presented at the World Universities Forum, 2009, and received considerable international interest.  UWA has a significant lead in this area; we now seek faculty partnerships to offer them locally, nationally and internationally.

The Speakers:
Neville Bruce is Director of the Centre for Integrated Human Studies, School of Anatomy & Human Biology, UWA (www.ihs.uwa.edu.au ). His major research and teaching interests centred on human reproduction and human biology. Over the past decade he broadened these interests to encompass human wellbeing from a psychological and biological perspective as a basis for developing a philosophy and practice for Integrated Human Studies. He had an active role in establishing the Australasian Society for Human Biology and at an extra curricular level has been involved in Scientists Against Nuclear Arms, the Peace Education Foundation and the WA Alternative Fuels Association. He is committed to furthering the discipline of Integrated Human Studies locally and internationally.

Steve Johnson is a lecturer at the Centre for Integrated Human Studies with the responsibility of curriculum development. He is currently working on the development of online first-year units in Integrated Human Studies, which use various e-learning technologies to promote inquiry, collaboration and knowledge construction. He is also completing a doctorate that investigates research writing as a process of semiotic inquiry and the use of diagramming software and portfolios as tools within instructional writing programs. Steve lives in Perth with his wife and two children and enjoys a game of golf when he has the time.

Professor Jeff Keelan, School of Women's and Infants' Health,  KEMH/The University of Western Australia

Inflammatory signalling in intrauterine tissues: identifying pharmacological targets

Speaker:
Jeff Keelan is Principal Research Fellow and Director of the Women and Infants Health Research Laboratories at King Edward Memorial Hospital/The University of Western Australia. His research is focused on the role and function of the placenta in normal and pathological pregnancies. His areas of expertise include placental endocrinology, immunology, inflammation, apoptosis, drug transport and metabolism. He also has a long standing interest in bioactive lipids in reproduction and has several ongoing projects in this area.

He was recruited to UWA in 2007 from the University of Auckland, where he was a Senior Lecturer in Pharmacology and head of the Pregnancy and Parturition group at the Liggins Institute. He has published 71 research papers, 11 review articles, 5 book chapters, and over 140 conference abstracts. He is funded by the March of Dimes Foundation, NHMRC, Raine Foundation, Bartholomew Trust and the Women and Infants Research Foundation.

Seminar:
Inflammation plays an important part in normal term labour, while excessive intrauterine inflammation is often causally associated with preterm labour and delivery. The extraplacental membranes are key tissues in this regard, in terms of their ability to respond to inflammatory stimuli and to drive labour and delivery. Surprisingly, intrauterine inflammation frequently occurs in the absence of detectable microbial infection, in which case anti-inflammatory therapies could be expected to be effective drugs for preventing preterm labour, extending pregnancy length, and improving fetal outcomes.

In this talk, Professor Keelan will discuss the mechanisms underlying inflammation-driven preterm labour, the signalling pathways involved in the activation of the local (placental) innate immune system, and some of the issues associated with selecting and evaluating potential pharmacological agents for preventing excessive intrauterine inflammation in pregnancy.