CCMB Major Research Areas
The Centre for Cellular and Molecular Biology (CCMB) has a strong research focus on the biology of metals. Prof Mercer is a recognized world leader in the molecular and cellular biology of copper; Prof Leigh Ackland is collaborating on aspects of this copper work. In addition, Prof Ackland has research programs on zinc, A/Prof Peter Beech is establishing a reputation for research excellence in the study of organelle division, Dr Jan West has expertise in understanding how muscles contract and A/Prof Cenk Suphioglu has recently established the Allergy Research Laboratory (ARL) in the study of grass pollen and peanut allergens.
Trace elements in heath and disease
Professor Julian Mercer, Professor Leigh Ackland
Trace elements such as zinc and copper are of vital importance for normal health and development. Disorders of trace elements are involved in important diseases such as Alzheimer’s disease as well as genetic diseases. How these elements are moved safely around the body is still not known in any detail. We aim to find the molecular mechanisms involved in trace element delivery to cells, and what goes wrong in trace element disorders. Our work is mainly focussed on copper and zinc.
Copper in health and diseases
Professor Julian Mercer, Professor Leigh Ackland, Dr Sharon La Fontaine, Dr Roxana Llanos
Prof Mercer's group is investigating how copper (Cu) is regulated in the body. Cu homeostasis is critical to the survival of all organisms. This is most dramatically illustrated in the human genetically inherited disorders, Menkes and Wilson diseases, where the balance of Cu is severely disrupted. Recently, research into the biology of Cu has entered a new and important stage in which the role of Cu in the pathogenesis of several common neurological diseases, such as Alzheimer’s and Parkinson’s diseases, is becoming widely recognized. Menkes disease is a fatal genetic copper deficiency disorder. Prof Mercer isolated the affected gene and continues to study the function of the Menkes protein in copper metabolism. This research may lead to better treatment of common disorders such as Alzheimer’s and Parkinson’s diseases, which appear to involve an imbalance of copper in the brain. An exciting recent discovery with our collaborators in the Anzac Institute in Sydney has shown that mutations in the Menkes gene are involved in some forms of peripheral motor neurone disease.
In collaboration with colleagues in the USA, Profs Mercer and Ackland are also investigating the physiological mechanisms involved in the uptake of copper from the diet and delivery of copper to fetuses (across the placenta) and newborns (in breast milk).
Protein networks in copper homeostasis
Dr Sharon La Fontaine and Professor Julian Mercer
Copper (Cu) is involved in a wide variety of physiological and pathological processes. Research into the molecular and cellular basis of the link between Cu, health and disease is still in its infancy. This knowledge is needed to understand how cells and organisms maintain an adequate balance of copper, how disruptions to this process lead to disease, and for the development of therapeutic approaches. Our research focus is the identification of new proteins and pathways involved in the maintenance of Cu homeostasis. We have identified and are characterizing several new candidates and pathways that regulate the activity of key Cu proteins, and hence overall Cu balance in the cell. Together, these proteins contribute towards ensuring cells have adequate Cu, while protecting cells from oxidative stress mediated by excess Cu. Some of these proteins have protective roles in diseases such as Alzheimer’s disease, cancer and diabetes. We are using a variety of molecular, biochemical, cell biology and proteomics approaches to study these proteins and Cu-regulated pathways in the cell.
Zinc – an essential nutrient
Professor Leigh Ackland, Associate Professor Cenk Suphioglu, Dr Agnes Michalczyk
Zinc deficiency is considered to be a public health problem that affects some communities including pregnant and breast-feeding women and newborn babies. Lack of zinc affects the immune system, impairs wound healing and may cause growth retardation, if severe. As there are no reliable tests for body zinc deficiency, we are developing new methods based on specific zinc transporting molecules, which can be used to detect cases of zinc deficiency. Moreover, we are investigating the importance of zinc homeostasis in human neuronal cells and its implications in neurodegenerative diseases such as Alzheimer’s disease.
Understanding how cancers spread around the body
Professor Leigh Ackland, Dr Agnes Michalczyk, Associate Professor Cenk Suphioglu
A major problem in treating cancers is that the cancer cells may have spread around the body and cannot be targeted by radiation or chemicals, without normal cells being affected. It is important to understand what makes cancer cells spread but this information cannot be obtained readily from studies of individuals. We have developed a cell culture model of the human breast that is enabling us to unravel the different stages in cancer progression. This may lead to the development of new anti-cancer strategies. In collaboration with the Peter MacCallum Cancer Institute, Prof Ackland has obtained an NHMRC grant to investigate breast cancer metastasis.
Phytoremediation to remove heavy metals from contaminated soils and heavy metal tolerance in cyanobacteria
Professor Leigh Ackland, Dr Agnes Michalczyk
Building on the expertise in metal biology at CCMB, Prof Ackland has developed collaborative projects with partners in China and India, to utilise plants for extracting heavy metals from contaminated soils. This entails an understanding of the molecular mechanisms of metal accumulation by plants and fungi. Studies are also underway to establish how cyanobacteria, an organism that has been on the planet for over 3 billion years, can tolerate metal stress, and the role of cellular heavy metal transport systems in metal homeostasis.
Grass pollen and peanut allergy: molecular analysis and novel intervention strategies
Associate Professor Cenk Suphioglu, Professor Leigh Ackland
Allergy is a clinically significant health problem in Australia (affecting up to 40% of the population and costing at least A$7.8 billion per annum). Grass pollens are a major component of the air flora during spring and summer and the most clinically significant cause of seasonal allergy in many countries. On the other hand, allergy to peanuts occurs in 1-3% of the population, predominantly affecting young children, that can result in a life-threatening anaphylactic reaction. A/Prof Suphioglu and members of his Allergy Research Laboratory (ARL) aims to target novel allergy intervention strategies by employing proteomics, phage display and yeast two-hybrid technologies to identify synthetic antagonists that neutralise allergy-triggering molecules for use in pharmacotherapy of allergy. Moreover, novel grass pollen and peanut allergens will be identified and new recombinant proteins and synthetic antagonists will provide for safer and more effective diagnosis and treatment of allergy. Indeed, our recent work has identified several antagonists to key molecules of the allergic reaction, showing promising results. In addition, analysis of peanut proteins under native conditions has revealed the formation of multi-allergen complexes upon digestion of the peanut (see http://www.abc.net.au/pm/content/2010/s2815963.htm).
Evolution of Organelle Division and Plant Pathology
Associate Professor Peter Beech
We study the molecular cell biology of mitochondrial and chloroplast division. Though we know that these two organelles arose from bacteria, we know little about how they are replicated and distributed at cell division. These are basic questions of biology and answers to them will help us understand how these respiratory and photosynthetic machines have been retained by cells for millions of years. Our model organisms are protists, such as the amoeba Dictyostelium and unicellular algae.
Of late, we are also becoming interested in the plant pathogen, Phytophthora. Phytophthora is an oomycete (P. cinnamomi is the causative agent of dieback and P. infestans of potato blight), and is thus more closely related to brown algae than it is to the fungi that it has been traditionally grouped with. We are searching for novel proteins in Phytophthora that may act as useful targets for the future control of this cancer of the plant world.
Developmental changes in muscle
Dr Jan West
|Jan West and members of the Muscle Research Laboratory are interested in changes in muscle structure and function during development. Recent projects are investigating the developmental changes in striated muscle (diaphragm and skeletal hindlimb muscles) from the spiny mouse (Acomys cahirinus) during normal development and after a hypoxic insult and assessing the protective role of creatine and melatonin supplementation. The precocial spiny mouse was chosen for this study as the relatively advanced development of key organs and systems (e.g. brain, lung, heart, kidney) at the time of birth is more similar to the term human fetus than other rodent species where maturation occurs postnatally. Our work has shown that a short period of intrapartum hypoxia caused significant structural and functional damage to the neonatal diaphragm. This damage was effectively prevented by creatine-loading the fetal diaphragm through maternal dietary supplementation during pregnancy. Our studies are continuing to investigate the role of creatine and melatonin (an antioxidant) in protecting other striated muscles (heart and hind limb) against hypoxic damage. This work is done in collaboration with Dr Hayley Dickinson and A/Prof David Walker at Monash Institute for Medical Research (Monash) and Dr Aaron Russell and Prof Rod Snow (Deakin University).||
What’s galling you? Insect taxonomy, ecology and molecular biology
Dr Anneke Veenstra
Gall midges from the family Cecidomyiidae are plant pests both in Australia and overseas. They inhibit the growth and reproduction of plants including ecologically valuable and economically important species. Despite many midges existing in Australia only 150 have been formally described. For formal description, the midge’s appearance and biology are insufficient – DNA analysis is necessary. Worldwide, DNA fingerprinting of Cecidomyiidae is in its infancy with few laboratories using this technique. Dr Veenstra is currently working on the formal description and phylogeny of two new species of gall midge from the genus Asphondylia.