Thursday 14th December, 2006 at 7pm
Speaker: Professor Sam F. Berkovic
Epilepsy Research Centre, University of Melbourne, Austin Health
Topic: THE BIOLOGY OF HUMAN EPILEPSY: A TWIN POWERED APPROACH
THE 2006 ROYAL SOCIETY OF VICTORIA RESEARCH MEDAL PRESENTATION was made by The Society's Patron, Professor David de Kretser AC, Governor of Victoria at this
meeting to Professor Sam F. Berkovic
"Bench to Bedside" has become a central theme of medical research. Yet, there is a mismatch between the increasing power of laboratory techniques, particularly molecular biology, and the intrinsic limitations of research on clinical populations. The challenge for the clinical researcher is to use imaginative techniques to maximise the benefit of basic research insights and techniques. In turn, incisive clinical data should be used to frame questions for the laboratory.
A central issue in any scientific experiment, but particularly studies in humans is variance. We are all different, both in our genetic makeup, our behaviour and our willingness to participate in studies. This poses particular problems for the clinical investigator although patients and families afflicted by a condition are often enthusiastic participants. Epilepsy, which affects over 2% of the population at some time in life, is a challenging condition to study because of it multiple forms and, sadly, because of the stigma that still surrounds it.
Twins are a remarkable "experiment of nature" that allow powerful questions to be asked - the biological scientist at the bench often uses littermates in animal experiments for similar reasons. The basic twin model of comparing identical twins that share all their genes, with non-identical twins where they share half, is a powerful method for detecting the components of "Nature versus Nurture" in individual conditions. This idea was first suggested in 1875 by Francis Galton, a cousin of Charles Darwin. We have used twins to look at the inheritance of the various forms of epilepsy with this classical twin model. Secondly, twins allow us to clarify aspects of classification - Are things that we think are different as clinicians really different? Using this strategy with the NHMRC Twin Register, we have identified those epilepsies with a major genetic component. Twins, however, are not very useful for identifying genes but here large families can provide remarkable information. Leveraging off the insights from twin data, we have identified large families with particular epilepsies, and identified a number of epilepsy genes. These code for ion channel subunits, regulating the flow of small ions in and out of nerve cells. Aberrations in their function thus represent a fundamental mechanism of epilepsy.
A third strategy with twins is that they can be used as matched pairs in a powerful way to look at various natural exposures, eg, obstetric factors, or therapeutic ones such as the effects of anti-epileptic medications. I will illustrate this by studies that have debunked the importance of obstetric factors in the causation of epilepsy. Fourth, twins can also be used to probe the reasons for extreme variation, when identical twins are discordant for a particular trait. We are using molecular techniques to understand the mechanisms of complexities in the genotype/phenotype relationship with twins.
These clinical and molecular genetic strategies are combined with studies of human epilepsy mutations introduced into mice by our collaborators at the Howard Florey Institute. This combined clinical and experimental laboratory approach provides insights that either approach alone would be incapable of revealing. The hope is to translate these insights into not only better diagnosis, which has already occurred, but also into better treatments.
Thursday 9th November, 2006 at 8pm
Speaker: Dr. Bill Birch
Museum Victoria (RSV Councillor)
Topic: URANIUM; MARVELLOUS OR MENACE - A VICTORIAN PERSPECTIVE
Uranium is a hot topic at present and is likely to remain so while Australia remains a key player in the production and export of uranium for energy purposes. Exploration for uranium is now increasing in order to build resources to augment the output from the three current operating mines, Olympic Dam and Beverley in South Australia and Ranger in the Northern Territory. So far, Victoria is not a player in this new exploration boom, but instead is seeing uranium used in some novel applications in geological dating, or geochronology.
As the heaviest of the naturally occurring elements, uranium averages about 2.3 ppm in the Earth's crust. Economic deposits of uranium are not that common, but small amounts of uranium-bearing minerals are widely distributed in many rocks types. Present-day natural uranium consists of about 99.3% of the 238U isotope and 0.7% of 235U. Both isotopes are radioactive, with well-established decay chains ending in stable isotopes of lead. The half life of 238U decaying to 206Pb is 4.47 billion years (about the age of the Earth), while 235U is about 6 times as radioactive, with a half life of 700 million years as it decays to 207Pb. Our ability to carry out precise analyses of the various isotopes in these two natural decay chains (as well as in a third series, involving 232Th decaying to 208Pb), has revolutionised geochronology over the past few decades. These analyses enable us to determine the crystallisation ages of minerals such as zircon, apatite, titanite and rutile, which may contain trace amounts of uranium in their crystal structures. Many rock-forming processes can now be accurately dated as a result. It is in the field of geochronology that Victorian geologists are applying the very latest technology.
The geochemical behaviour of uranium, especially how it moves around in groundwater, determines what minerals it forms and where they are found. Uranium is never found as a metal, but instead exists mainly in the oxidation states U6+ and U4+. In aqueous solutions, U6+ is present mainly as the uranyl ion (UO2)2+, which forms the basis for many uranium minerals. There are over 230 minerals containing essential uranium. Most of them are 'secondary' species, such as oxides, hydroxides, carbonates, phosphates, vanadates and silicates, forming attractive bright yellow, green or orange earthy masses or crystals. These secondary minerals are derived mainly by alteration of primary UO2, known as uraninite. In most occurrences, uraninite is a dense black compound (with the old name pitchblende) in which the original crystal structure has been destroyed by its own radiation, a state referred to as metamict. Concentrations of uraninite are the prime ore targets for mining companies.
In Australia and elsewhere, uranium deposits can be classified by their geological character. The Olympic Dam deposit, currently the world’s largest producer, is a vast hematite breccia complex with disseminated uraninite and several other U-bearing species formed about 1590 million years ago. The scores of uranium occurrences in the Pine Creek Inlier in Arnhem Land, containing the well-known Ranger and Jabiluka deposits, are mostly related to unconformities, while those at Beverley and Honeymoon in South Australia are hosted by sandstones.
While lacking any economic deposits, Victoria has widespread occurrences of uranium present in some common minerals, such as zircon, titanite, apatite and monazite. These have been the basis for the fission-track dating method, in which Victorian researchers were pioneers during the early 1970s. As well as allowing many igneous rocks such as granite and basalt to be dated, the method also enables the thermal histories of thick sequences of sedimentary rocks, such as those of the Otway Basin, to be modelled. This is a vital tool in exploration for potential new oil and gas fields. Airborne radiometric maps of Victoria show that rocks richest in uranium broadly correspond with some belts of granitic rocks, such as the Harcourt Granite, the outer zone of the Cobaw Granite, and those forming the You Yangs. Uranium and thorium-bearing minerals such as monazite and allanite are likely to be the cause of these signals. Elsewhere in Victoria, secondary uranium minerals have been found in several granites, such as at Mt. Wills and Mt. Wycheproof, suggesting that these probably contain traces of primary uraninite.
By far the most interesting uranium deposit in Victoria is also unique in the field of mineralogy. In the late 1950s there was considerable excitement over the discovery of a secondary uranium mineral, torbernite, in a granite quarry a few miles south of the town of Lake Boga, near Swan Hill. While this had the scintillometer ticking, it was soon recognised as being uneconomic. The quarry has become the major source of crushed rock in the region, and has also provided collectors with a host of interesting and unusual minerals in beautiful, if small crystals. Amongst these are five uranium-bearing minerals, two of which, torbernite and saleeite, are reasonably common around the world. Another, metanatroautunite, is known only from a handful of other world locations, while two are known only from the Lake Boga quarry. Ulrichite, a calcium copper uranium phosphate, was first described from Lake Boga in 1988 and named for George Ulrich, a pioneer Victorian mineralogist. The other new uranium mineral is currently undergoing investigation.
These uranium minerals resulted from the alteration of microscopic primary uraninite crystals disseminated through the granite. When this alteration occurred is of interest, as it was probably associated with weathering of the uppermost levels of the granite. Perhaps these uranium minerals could provide an indication of climate fluctuations during that weathering period, as they might be expected to crystallise when groundwater was more abundant and conditions were warmer, rather than during the cold and dry conditions characteristic of glacial periods. In a study funded by a Potter Foundation grant, crystals of the Lake Boga minerals are being dated by a U-Th technique, a method never before applied systematically to such an occurrence. Results to date confirm that most of the minerals have formed during the period between 100,000 and 500,000 years ago. The connection between crystallisation and climate however has not yet been conclusively demonstrated, but more data may show this link.
These innovative techniques in uranium-based geochronology are ensuring that Victorian occurrences receive scientific attention, despite the lack of prospectivity for the metal itself.
Thursday 12th October, 2006 at 8pm
Speaker: Dr. Brendan Burns
RSA Eureka 2005 Winner
The University of NSW, School of Biotechnology & Biomolecular Sciences & Australian Centre for Astrobiology
Topic: THE LIVING ROCKS OF AUSTRALIA: A WINDOW TO OUR PAST
Are we alone? What is the origin of life? These are some of the most profound questions of humankind, capturing the imagination of scientists and lay people alike for centuries. We are tackling some of these questions in earnest in the study of the famous living and fossil stromatolites in Australia. The strategic goal of this research is to comprehensively study the functional complexity of modern stromatolites and their fossil counterparts in Australia, as model systems for understanding the intricate interactions between microorganisms and their physical environment and their roles in the wider biosphere. One of the major challenges in science is to identify modern living systems that present unique opportunities to address fundamental questions in diverse fields ranging from microbiology, geology, evolution, chemical biology, functional genomics, and biotechnology. Stromatolites represent such a system.
One of the earliest pieces of evidence of planetary life is contained in the microfossils of stromatolites (or 'living rocks'). They have been present on Earth for more than 3 billion years, making them one of the oldest known and most resilient of ecosystems. Stromatolites are biosedimentary structures produced by the sediment-trapping, binding and/or precipitation activity of resident microbial communities, in particular cyanobacteria (or 'blue-green algae'). The morphological features of modern stromatolites are considered to closely resemble ancient stromatolites, and thus may represent the oldest examples of life on Earth. Many important steps in evolution may also have occurred within stromatolites owing to the close proximity of diverse microorganisms and microhabitats.
In addition, stromatolites are also hypothesised to have been responsible for the initial mass production of free oxygen and thus the subsequent evolution of animal life. Thus, modern stromatolites are a significant resource for studying the origin, evolution, and distribution of life, particularly the physiological processes that shape planetary biology and leave preserved biosignatures in fossils on Earth and, potentially, distant biospheres. Australia not only has some of the oldest fossilised examples of these biotic structures but also possesses some of the most extensive living examples of these aquatic ecosystems. Shark Bay in Western Australia is notable for its living stromatolites, and is listed as a World Heritage Site. Through the application of a rational and integrated approach, our research has provided valuable insights into these evolutionally significant biological systems, and made substantial contributions to the exciting and rapidly developing field of astrobiology.
Specifically, our work has focused on:
1. Documenting for the first time the vast microbial diversity in living stromatolites.
2. Determining the preservation of geochemical signals and biological markers in modern stromatolites to allow better comparisons with fossil counterparts.
3. Characterising potentially innovative strategies for stress response in stromatolite organisms and contributing to an Environmentally Sustainable Australia.
4. Exploiting the untapped reservoir of potential novel bioactivities in stromatolites.
5. Understanding how such microbial systems have existed throughout geological time and thus predicting environments for survival in extraterrestrial systems.
6. Ensuring the conservation of one of Australia’s richest biological resources.
In addressing these diverse fundamental areas, we have adopted a multidisciplinary approach to logically and rationally advance the field. We were one of the first to use modern molecular methods to study the biology of stromatolites, revealing that geographically distinct stromatolites are often characterised and appear to be dominated by specific cyanobacteria. We also conducted the first polyphasic examination of the microbial communities of stromatolites, combining culture-
dependent and culture-independent nucleic acid based methods. This pioneering study revealed that the Shark Bay stromatolites supported and unexpected range of metabolically and phylogenetically diverse prokaryotes and led to the development of new molecular tools and research directions. The cyanobacteria identified were mainly filamentous, a characteristic known to aid sediment trapping in stromatolites and likely to be important in the formation of the Shark Bay stromatolites. We also discovered free-living Prochloron species from these stromatolites, the first time this cyanobacterium has been observed not in symbiosis. microbial community was also characterised by numerous heterotrophic bacteria important that are important in nutrient cycling, such as the alpha-Proteobacteria, demonstrating that these are extremely dynamic systems. In addition members of the halophilic and methanogenic archaea were identified. This program of research was the first to reveal such a diversity of archaea associated with stromatolites.
Building on this excellent platform, we used these results as a framework to conduct in-depth analyses on stromatolite systems combining both biological and geological expertises. These include:
* Isolation of novel organisms: new species of archaea were isolated for the first time from these stromatolites, with several physiological characteristics distinct from other known archaea. A new species Halococcus hamelinae was characterised and named.
* Unique stress response in stromatolites: the first examination of salt tolerance in these stromatolites was undertaken at both physiological and molecular levels. NMR spectroscopy was employed to test for the presence and accumulation of specific osmoprotectants, and genetic and proteomic methods employed to comprehensively understand stress responses. Results indicate unique features that may indicate the synthesis of novel osmoprotectants.
* Chemical biology analyses: lipid profiling of these systems was conducted as a powerful way of revealing microbial community structure and for comparing modern day stromatolite populations with those from fossil sediments. Specific lipid signatures were revealed and their potential as biomarkers evaluated. There is the intriguing potential for using the knowledge gained in the rational search and detection of possible biosignatures of life on other planets.
* Stromatolite bioprospecting: for the first time the genetic potential of secondary metabolite-producing cyanobacteria in stromatolites was shown. Analysis indicated that genes identified are responsible for the production of potentially novel secondary metabolites, such as those with antibacterial or antifungal effects. Putative anti-cancer and anti-protozoal activity was also observed in several isolates, findings of significant biotechnological interest. Furthermore, the vast genetic and chemical diversity of these systems is being accessed, employing recent principles of functional metagenomic analysis to rationally assess the biotechnological potential of unculturable stromatolite microorganisms.
Aside from the advancement of human knowledge, this research has the potential to impact on areas in Australia such as economics, theology, and ethics, as well as other philosophical issues that may ultimately define who we are. From an applied perspective, in addition to ‘bioprospecting’, commercial applications of this work include exploiting osmoprotection mechanisms discovered in stromatolite organisms for the genetic enhancement of drought and salinity tolerance in crop plants in salinity effected regions. This has potentially huge economic benefits for Australia, particularly as novel stromatolite microorganisms may possess unique and efficient salt tolerance mechanisms. Apart from basic and applied benefits, we believe our work is absolutely intrinsic to the conservation of such a fragile and unique ecosystem. Although these systems have survived for 75% of Earth’s entire history they are still very susceptible to human impact. Our results have already suggested a loss of biodiversity over a relatively short period of time, and this information is critical for the management and conservation of these unique biological resources. We are continuing to work with conservation bodies to improve their environmental management to ensure the preservation of these unique ‘living rocks.’
Thursday 14th September, 2006 at 8pm
Speaker: Professor John Long
Head of Sciences, Museum Victoria
Topic: THE ORIGIN OF JAWED FISH; NEW GONDWANA DISCOVERIES OROGENIC SYSTEM
Perhaps the two most significant steps in the evolution of the back-bone animals have been the origins of jaws and the transition from fish to land animal (tetrapods). The first jawed fishes (gnathostomes) are known only from associated fossil fragments which imply they had jaws. Remains of shark-like scales date back as far as the Ordovician Period (c. 480 million years) not long after the first fishes had appeared. The origin of jaws in fishes has commonly been implied as the modification of the anterior gill arches (forwards of the hyoid arch) being modified as jaws, by serial homology with living fish visceral skeletons, and the fact that gill arches often bear teeth anyhow. Which group of the many extinct jawless fishes gave rise to the ganthostomes has long been debated. A new approach to solving the origin of jaws in vertebrates has been proposed which involves a developmental model coupled with palaeontological evidence, favouring the Osteostracans as the group most likely to have evolved jaws.
The first definite fossil teeth appear much later by the start of the Devonian Period (c. 410 million years ago). The oldest fossil forms with jaws are the acanthodians (spiny sharks) a poorly known group of extinct fishes. Sharks make an appearance in the Devonian, known only from teeth, scales and spines, until around. 400 may when the first articulated fossil shark, Doliodus, from Canada occurs. Although advanced placoderms have jaws and teeth, the earliest forms remain enigmatic as to their feeding mechanisms. A recent paper by Smith & Johanson argued a dual origin of teeth in vertebrates, but critics have rebuffed this saying that as the basal placoderm jaws are unknown, it’s possible that all placoderms evolved teeth at the same time. By the start of the Devonian many groups of osteichthyans (true bony fishes) are known, mostly from the famous Yunnan deposits of China. The gaps, or ghost records, of some of these linage have remained enigmatic until recently, but new discoveries from Australia and Antarctica are filling in these gaps and showing the biogeographic distribution of these groups, and their relevance to the origin of tetrapods.
The oldest members of the ray-finned fishes are known from scales and teeth of late Silurian age, with the oldest preserved braincase coming from the early Devonian of Australia. Perfect, 3-D skeletons of these palaeoniscoids from the Late Devonian Gogo Formation provide the best anatomical information on the origins and relationships of the group, with new work in progress at the museum by Brian Choo.
The most basal sarcopterygian fish si Onychodus, also best known from 3-D Gogo specimens, recently described (Andrews et al 2006). Further older examples of this clade have been identified form the Early Devonian deposits at Buchan (Johanson et al in press). The oldest and best preserved lungfishes are known from China, with many early species also known from Australia (Taemas, NSW, Buchan, Victoria).
Gogonasus, new specimen discovered by Museum Victoria 2005
The most advanced clade of fishes leading to tetrapods include the forms having only one pair of nostrils, the tetrapodomorphans. The oldest members of this clade come from China, with other basal forms known from Australia (including the oldest known rhiozodontids, from Victoria, NSW, and Queensland). The “Osteolepiformes” are now recognised as a paraphyletic group, with fishes like Eusthenopteron (commonly used in text-books to represent the fish-tetrapod transition) being no longer appropriate. New research by the Museum’s team has shown that some apparently basal-looking fishes, like Gogonasus (from Gogo Fm) are far more advanced in their fin and inner ear structure than previously thought. Such new discoveries add significant new pieces to the puzzler of tetrapod origins, and give fresh perspectives on the functional morphology of how fishes went from water-respiring swimmers, to air-breathing walkers on land.
Some relevant recent references:
ANDREWS, S.M., LONG, J.A., AHLBERG, P.E. , CAMPBELL, K.S.W. & BARWICK, R.E. 2006. Onychodus jandemarrai, new species, from the Late Devonian Gogo Formation of Western Australia. Transactions of the Royal Society of Edinburgh, Earth Sciences 96 (3): 197-307
JOHANSON, Z., LONG, J.A., JANVIER, P. & TALENT, J. 2006. Oldest coelacanth from the Early Devonian of Australia. Biology Letters 3 (1): on line pub March 2006
LONG, J.A., HALL, B.K., McNAMARA, K.J. & SMITH, M.M. in press.. The phylogenetic origin of jaws in vertebrates: developmental constraints and heterochony. Kirtlandia, Cleveland Musuem of Natural History, special volume for Michael Williams. MS 20pp, 3 figs.
LONG, J.A., YOUNG, G.C., HOLLAND, T., SENDEN, T.J. & FITZGERALD, E. In press. An exceptional Devonian fish from Australia sheds light on tetrapod evolution. Nature (accepted August 2006).
Thursday 10th August, 2006 at 7pm
Speaker: Dr. Neil Adams
Regional Manager Antarctic Meteorological Section, Tasmania and Antarctica Region, Bureau of Meteorology, Hobart
Topic: ANTARCTICA – THE CLIMATE, THE WEATHER AND THE BUREAU OF METEOROLOGY
The Bureau of Meteorology has been working continuously in Antarctica, alongside the Australian Antarctic Division, since the first Australian Antarctic expedition of 1947. The Bureau maintains observing offices at Casey, Davis, Mawson and in the sub-Antarctic at Macquarie Island. These offices are responsible for making routine surface and upper air observations as part of the global climate record. The observations are also essential for assimilation into regional and global Numerical Weather Prediction systems, run both locally and internationally. The Bureau also provides weather forecasting support over the summer months to the Australian Antarctic program, with weather forecasters stationed at Casey and/or Davis. Forecasting duties include support of fixed and rotary winged operations, boating, scientific field work and high seas forecasting. The Bureau is also called upon to provide sea-ice analyses to assist in navigation at sea.
This talk will cover the range of activities undertaken by the Bureau in Antarctica in support of Antarctic science, from operational tasks through to Antarctic atmospheric research and will discuss the unique challenges posted by the Antarctic environment.
13 July 2006
Assoc. Professor Sandra Rees
Chair, Department of Anatomy, University of Melbourne
"BRAIN DEVELOPMENT - THE ADVERSE EFFECTS OF ALCOHOL, INFECTION OR LACK OF OXYGEN DURING PREGNANCY"
There is now compelling evidence that many neurological disorders which become apparent after birth have their origins during fetal life. For example, epidemiological studies have shown that cerebral palsy most frequently results from prenatal rather than perinatal or postnatal insults. Schizophrenia, one of the most debilitating of mental disorders, affecting ~1% of the population, cannot be accounted for entirely by genetic inheritance. On the basis of histological and neurochemical observations it has been proposed that prenatal insults result in a vulnerability of the developing brain, predisposing an individual with risk factors (such as genetic inheritance) to develop the symptoms of schizophrenia in the teenage or young adult years. Other disorders such as epilepsy and autism are also thought to result in part from neurodevelopmental problems. It is critical that we develop an understanding of the events that can go wrong during pregnancy so that we can devise strategies to intervene and prevent or ameliorate the effects of these adverse events.
The fetus is totally dependent on the placenta and umbilical cord for an adequate supply of oxygen and nutrients during pregnancy. Interruption to this supply could be sudden (acute) such as in umbilical cord occlusion or of a more long lasting (chronic) form due for example to impaired placental function resulting from maternal high blood pressure or tobacco smoking or partial placental detachment. Recent clinical studies have indicated that maternal or intrauterine infection/inflammation might also play a critical role in perinatal brain damage; there are significant associations between maternal infection, preterm birth, neonatal brain damage and long-term disabilities including cerebral palsy. Maternal alcohol consumption is known to have damaging effects on the developing brain and it is now thought that the brain might be vulnerable to binge drinking in addition to the more widely acknowledged effects of chronic alcoholism.
In order to understand the mechanisms involved in these insults we have developed models to mimic situations that might occur during human pregnancy. From these studies we have found that at mid-gestation even a relatively brief period of reduced oxygen supply to the brain can cause nerve cells and their connections (fibres) to die. If there is a prolonged but more mild reduction in oxygen and nutrients connections between nerve cells can also be affected and myelin, the fatty covering around nerve fibres that aids their function, is poorly formed. The equivalent of a binge drinking episode in late gestation can also damage nerve fibres in the brain and most likely affect brain function in the areas involved. Exposure to an endotoxin (modelling inflammation) can significantly affect nerve fibres and ultimately this would affect nerve cells. By comparing findings in animal models with altered pathology and function in neurological disorders we are beginning to define the types of insult that could underlie some of the neurological disorders thought to have a perinatal origin.
Currently there are no effective strategies to ameliorate human fetal and neonatal brain damage. Developing such treatments is currently one of the most important areas in perinatal medicine not least because of the increasing survival rate of very premature infants who are at high risk for brain damage. We have begun to trial therapeutic agents for brain damage in our animal models and the preliminary results will be discussed in my presentation. Creating an ideal extrauterine environment for preterm and term infants with brain injury or poor brain development will also be essential if we are to facilitate appropriate development of the brain after birth. Finding effective treatments for brain damage and then developing the most effective means of encouraging brain development postnatally are both vital areas of endeavour if we are to help infants develop their maximum potential and reduce the enormous social, economic and educational burden which must be borne by the individual and society in general when things go wrong during pregnancy.
8 June 2006
Prof. Timothy New
Chair, Department of Zoology, La Trobe University
"DESIGNING AND IMPLEMENTING AUSTRALIA'S NATIONAL ACTION PLAN FOR BUTTERFLY CONSERVATION"
The 'Butterfly Action Plan' (BAP; Sands & New 2002) was the first attempt to systematically and comprehensively appraise the conservation status and needs of any group of invertebrates in Australia. It deals with 654 species and subspecies of the most adequately-documented insect group, and has been important also in introducing the background of invertebrate conservation to many people to whom these animals were previously a mystery.
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