School of Chemistry and Biochemistry

Research

null

Further information

  • A-Z Staff Research Profiles
  • Find out what our postgraduates are researching

Research


Staff publications

2011 | 20102009 | 2008 | 2007 | 2006


Search

Laboratory Research Group Leaders

 
 
null

Peter Arthur

Associate Professor
Reactive Oxygen Species and Oxidative Stress

Our research focuses on how oxidative stress caused by reactive oxygen species (ROS) alters protein function. Our work, and the work of others, has established that multiple proteins are sensitive to ROS, which means oxidative stress can have widespread impact on many cellular processes (metabolic pathways, ion transport, protein synthesis, protein degradation, gene expression, signal transduction pathways) to profoundly affect cell and tissue function. This research has biomedical applications because oxidative stress has been proposed to initiate or exacerbate pathology associated with many chronic diseases and conditions. Examples include Alzheimer’s disease, atherosclerosis, cancer, diabetes, heart disease, HIV/AIDS, kidney disease, liver disease, muscular dystrophy, Parkinson's disease, Rheumatoid arthritis and aging.

For further information see my staff profile

Back to top

 
null

Paul Attwood

Professor
Structure and Function of Enzymes

For further information see my staff profile

Back to top

 
null

Boris Baer

Professor
More than Honey

Honeybees are of central importance for human food production, as they pollinate more than 80 crops of agricultural interest. About a third of what you eat depends on bee pollination, with an estimated value of 4-6 bn A$ annually for the Australian agricultural sector. The pollination services of honeybees for agricultural crops and ecosystems have largely been taken for granted but we currently face a dramatic worldwide decline in bees, and spreading parasites contribute towards these losses. Australia has so far been spared major losses of honeybees, although they are declining as well and catastrophic losses caused by newly invading pathogens are expected to occur in the coming decade. The Centre for Integrative Bee Research (CIBER) is a cross disciplinary team of scientists that conduct research to better understand honeybees and to provide support for the honeybee industry to overcome present and future problems. What we need is to breed better bees that are capable to cope with the challenges. Consequently we need to study the reproductive biology and immunity of honeybees. To do this we use an approach that is referred to as evolutionary proteomics, where we want to understand evolutionary dynamics such as the functioning of the immune system or sexual reproduction on the molecular scale. To do this we use genomic, proteomic and metabolomics approaches.

Back to top

 
null

Murray Baker

Professor
Synthetic Chemistry

We aim to apply our skills in synthesis to problems in areas such as catalysis, nanotechnology, surface science, biological chemistry/medicine, polymer science, molecular recognition, and sensors.

For further information see my staff profile

Back to top

 
 
null

Charlie Bond

Professor
Structural Biology

Group members: Agata Sadowska and Mihwa Lee

Structural Biology research involves building a three-dimensional picture of biological molecules to shed light on the molecular interactions and events which drive many of the fundamental processes of life. Investigations in my lab address proteins of relevance to human health, including nucleic acid processing proteins involved in regulating gene expression, and enzymes essential to the survival of life-threatening microbes, which may be drug targets. Recent research from the Bond lab has received media attention locally, nationally and internationally.

For further information see my website and staff profile

Back to top

 

null

Bernard Callus

Dr
Apoptosis and Cancer Signalling

Our research focuses on the mechanisms of apoptosis (programmed cell death) as well as the signalling pathways that regulate apoptosis. Particular focus is given to how abnormal apoptotic signalling contributes to the development of liver cancer. Typically, cancer cells are profoundly resistant to apoptotic stimuli, e.g. chemotherapeutic drugs or irradiation, and this apoptotic resistance is considered to be an essential aspect of tumour development. Often this is due to amplification of oncogenes, e.g. Bcl-2, or the loss of tumour suppressors, e.g. p53, or a combination of both which impart apoptotic resistance in cells.

Our research incorporates molecular biology to manipulate the expression and/or function of oncogenes and tumour suppressors in cells to examine how they impact on apoptotic mechanisms and the signalling pathways that regulate them. The aim here is to identify novel regulators of apoptotic pathways and tumorigenesis as candidates for drug design leading to the development of new therapies to be used either alone or in combination with existing chemotherapeutics to kill cancer cells.

Worldwide, liver cancer is the fifth most prominent cancer and the third highest cause of cancer-related deaths. There is mounting evidence to suggest that liver progenitor cells (LPCs) are a potential source of liver cancers, however, the underlying mechanisms that transform LPCs to cause liver tumours remain largely unknown. Hence we also investigate the molecular changes, e.g. proteins, mRNAs and micro-RNAs (miRs), associated with liver progenitor cell (LPCs) transformation to identify critical initiating molecular events in liver cancer. Using a variety of molecular approaches we aim to identify the key mechanisms that underpin liver cancer arising from transformed LPCs. We focus on genes and miRs involved in apoptotic and cell cycle regulation.

For further information see my staff profile

Back to top

 
 
null

Reto Dorta

Associate Professor
Organometallic Chemistry and Catalysis

Our research is directed toward the preparation of reactive transition metal complexes for stoichiometric and catalytic applications. We focus our attention on the development of new chiral and non-chiral auxiliary ligand systems which are able to bind, activate and functionalize the substrates at the metal center. The ultimate goal of the research program is to identify new ligand families and their corresponding metal complexes for new, more selective or more widely applicable catalytic transformations

For further information see my staff profile and website

Back to top

 
 

nullGavin  Flematti

Dr
Natural Products and Chemical Ecology

We are particularly interested in bioactive compounds that are involved in signalling and communication. We make use of sophisticated analytical instruments such as GC-MS and HPLC-MS to aid in the detection and isolation of bioactive compounds, which are usually identified using NMR spectroscopy and high resolution mass spectrometry techniques. Depending on the structure, these compounds may require confirmation through synthesis.

For further information see my staff profile

Back to top

 
 
null
null

Peter Hartmann & Professor Donna Geddes

Winthrop Professor / Research Assistant Professor
Physiology and Biochemistry of Milk Synthesis, Secretion and Removal

Group members: Lynda Chadwick, Cathy Garbin, Jacqueline Kent, Ching Tat Lai, Marnie Rowan, Jill Sherriff, Melinda Boss, Anna Skwierczynska and Anna Hepworth

Winthrop Professor Peter Hartmann leads a large research group that carries out both basic and applied lactation research with women and infants. Despite a plethora of evidence showing breast milk is the best nutrition many women fail to sustain exclusive breastfeeding for 6 months as recommended by WHO. The aim of this group is to provide an evidence base for clinical protocols and management of lactation difficulties. To achieve this objective a fundamental research into the physiology and biochemistry of milk synthesis milk secretion, milk ejection, the mechanics of breastfeeding and the control of infant appetite is carried out.

Back to top

 
 
null

K Swaminathan Iyer

Dr
Nanobiotechnology

Nanobiotechnology is a branch of nanotechnology with biological and biochemical applications. Our research explores the synthesis, characterisation and application of novel polymer based formulations for biomedical applications. Using surface chemistry on tailor polymers we aim to track and deliver payloads to image and improve the outcome in various medical emergencies.

For further information see my staff profile

Back to top

 
 
image of Amir Karton

Amir Karton

Assistant Professor
Computational and Theoretical Chemistry

During the past decade, computational chemistry has had an increasingly important impact on almost all branches of chemistry as a powerful approach for solving chemical problems at the molecular level. The increasing computational power provided by supercomputers and the emergence of highly accurate theoretical procedures make contemporary computational chemistry one of the most detailed “microscopes” currently available for examining the atomic and electronic details of molecular processes. In my lab we use supercomputers in conjunction with very accurate theoretical methods to elucidate the reaction paths, kinetics, and the mechanisms in salient organic, organometallic and enzymatic systems.

For further information see my staff profile

Back to top

 
null

Dylan Jayatilaka

Professor
Theoretical and Computational Chemistry

I am interested in a number of areas, including:

Quantum chemistry: using quantum mechanics to calculate molecular properties e.g. shapes, dipole moments, polarisabilities. We use existing computer programs and we write our own too.

Chemical concepts from quantum mechanics. Although quantum mechanics can produce calculated properties, it is often difficult to understand and interpret these properties in terms of “atoms” and “bonds” and all the usual terms that chemists use. I'm interested in developing theories and methods to do this.

Crystallography and diffraction: I'm interested in using diffraction experiments to improve quantum chemistry calculations, and vice versa, using quantum chemistry to improve measurements from X-ray and polarized neutron diffraction experiments.

Development of reusable software. I have written a program library called Tonto which makes developing new quantum chemistry and crystallography methods easier than normal.

Visualisation of complex chemical data. Together with Prof. Spackman, I have developed a program called Crystal Explorer to visualize crystal structure packing information in high quality 3D graphics.

For further information see my staff profile

Back to top

 
 
null

George Koutsantonis

Professor
Metals in Chemistry and Nanochemistry

Group members:  Rebecca Fuller

Our group is interested in the role of metals in functional materials. While the role played by metals in materials is still evolving and there is an increasing effort to incorporate redox–active centres into many materials, e.g. conducting polymers, in an effort to create highly efficient redox conductivity for sensor, catalytic, photochemical and photoelectronic applications. We are participating members of the WA Centre of Excellence in Nanochemistry.

For further information see my staff profile

Back to top

 
 
null

Ryan Lister

Winthrop Professor
Exploring the Epigenome

Just as the fixed notes of a musical instrument can be played in different combinations, orders and strengths to create unique songs, different cells in a complex multicellular organism can produce their distinctive form and function by each expressing particular combinations of genes from the genome. By modulating accessibility to the information encoded in the genome, epigenetic modifications can affect gene activation and repression to execute distinct transcriptional programs and impart a heritable state of transcriptional activity. In essence, the epigenome is a regulatory code that is superimposed upon the genome that can modify the cellular readout of the underlying information encoded in the DNA sequence. Developing a comprehensive understanding of how the cell utilizes epigenetic modifications is essential in order to both understand the critical roles it plays in eukaryotic development and stress response, and to develop effective strategies to remedy its disruption in disease states.

We use advanced DNA sequencing, molecular, genetic and computational techniques in a diverse range of complex multicellular organisms, including plants, humans, mice, and social insects, to study the epigenome and epigenetic mechanisms at the molecular scale. Recent advances in DNA sequencing technology now enable us to rapidly identify precisely where epigenetic modifications, such as DNA methylation and histone modifications, occur throughout entire plant and animal genomes1-3. The research in my laboratory aims to understand how the information encoded in the DNA of plant and animal genomes is controlled by epigenetic mechanisms during development, how the epigenome may be altered by the surrounding environment, and to develop molecular tools to reprogram it.

For further information see my website

Back to top

 

image of Winthrop Professor Paual LowPaul Low

Winthrop Professor
Organometallic Chemistry and Molecular Electronics

Molecular materials allow the fascinating range of optical, electronic and magnetic properties offered by molecules, and which can be manipulated through control over molecular composition and structure, to be applied in device platforms. We are particularly interested in understanding how changes in redox state can influence molecular electronic structure and hence opto-electronic properties, with particular emphasis on molecular electronic applications. To do this we employ a wide range of synthetic, electrochemical, spectroelectrochemical and computational methods to gain insight concerning the redox-mediated structure-property relationships in organometallic and organic molecular materials, in collaboration with many other groups in the School, across the University and around the world.

For further information see my staff profile

Back to top

 
Ludwig2013

Martha Ludwig

Associate Professor
Molecular Evolution of Photosynthetic Pathways

Terrestrial plants are typically grouped according to the biochemical pathway they use to fix atmospheric CO2 into carbohydrates – the so-called C3 plants, which include crop species such as rice and wheat as well as nearly all trees; the C4 plants, which include highly productive crop plants like corn and sugarcane; and the Crassulacean Acid Metabolism (CAM) plants, which include cactuses, orchids and pineapple. C4 and CAM plants evolved from C3 plants, and some groups of plants have left “evolutionary footprints” that give us insights into how this process has occurred at the molecular level.

The aim of the work in the lab is to understand the molecular biology and genetics, biochemistry and cell biology of the enzymes in the C4 photosynthetic pathway. This includes the identification of the control regions of the genes coding for these enzymes. We do this by comparing the proteins and genes of C4 plants to those of closely related C3 plants. The information we gain will be used to make informed and strategic decisions regarding the transfer of particular C4 enzymes, or an entire C4 pathway, into C3 plants to increase yield while restricting negative impacts on the environment.

For further information see my staff profile

Back to top

 
null

Thomas Martin

Associate Professor
Cellular Signalling and Protein Interaction

We are interested in cellular signalling and how this impacts on plant development and function. Learning about this will help us to identify mechanisms by which plants can be improved to be for example drought, salt or stress resistant or to generate higher yields. These are desirable traits for plants growing under the harsh environmental conditions in Australia.

To this end we investigate two gene families related to stress responses in plants:

a) One is a class of histone deacetylases (HD2) found only in plants. These are proteins involved in the regulation of gene expression by deacetylation of histones which causes changes in chromatin structure. Some of these plant specific histone deacetylases were reported to lead to increased drought and salt tolerance when overexpressed in Arabidopsis (1).

b) The other is a family of nitrilases which are potentially involved in cyanide detoxification and plant hormone biosynthesis (2).

Using a state of the art protein interaction system named Bimolecular Fluorescent Complementation (Fig 1) we have shown that members of the plant specific histone deacetylases and the nitrilases interact with 14-3-3 proteins (Fig 2 a and b). These 14-3-3 proteins bind to other proteins and regulate their activity, cellular localisation or stability in response to intracellular or extracellular signals and thereby impact on protein activities and functions (3). Our interest is to understand what the impact of this regulatory interaction between 14-3-3 proteins and histone deacetylases and 14-3-3 proteins and nitrilases is and how this contributes to normal plant function, especially under stress conditions.

 null

Figure 1: The principle of Biomolecular Fluorescence Complementation (BiFC). Two non-fluorescent parts of the Yellow Fluorescent Protein (YFP) are fused to two proteins assumed to interact, for example a 14-3-3 protein and a potentially 14-3-3 regulated protein (A and B). If these proteins do not interact (left) we will not observe fluorescence. Interaction of A with B (right) reconstitutes a functional YFP and fluorescence can be observed using fluorescence microscopy The great advantage of this system is that it can be used in living plants instead of looking at interactions in vitro. (from 4).

 

null  null

Figure 2: Interaction of 14-3-3 proteisn with histone deacetylase (a) and nitrilase 1 (b) demonstrated using Biomolecular Fluorescence Complementation (BiFC and Confocal microscopy).

(a) 14-3-3 mu was tested for interaction with the plant specific histone deacetylase HD2C. Interaction was found to occur in the nucleus (N) and nucleolus (No). (b) Interaction of 14-3-3 proteins with nitrilase 1 after induction of cell death. The interaction occurs usually in the cytoplasm of plant cells but localises to round structures after cell death induction as shown in figure b.

For further information see my staff profile

 Back to top
 
null

Allan McKinley

Professor
Spectroscopy of Reactive Intermediates

My research interests involve: applications of spectroscopy for the detection and characterization of reactive intermediates, theoretical modelling of the bonding in radicals, analysis and remediation of contaminated groundwater, and biological applications of Electron Spin Resonance spectroscopy.

For further information see my staff profile

Back to top

 
 
null

Harvey Millar

Winthrop Professor
Biomolecular Networks

Cellular processes are directed by genes, orchestrated by proteins and delivered through fluxes of metabolites. These elements make up the cellular molecular network. The rapid accumulation of network-related data from many species provides unprecedented opportunities to study the function and evolution of these biological systems. The basic goal of network comparison is to uncover identical or similar sub-networks by mapping changes in one network to another. Such analysis can reveal important biological links, and explain how networks evolved, how natural variation alters networks, and how engineering of networks can provide novel biological outcomes. Using a combination of protein separation techniques, mass spectrometry and informatics, my research group is focused on understand the compartmentation of cellular functions in cellular organelles and the networks of molecules that define cell energy metabolism and its impact on real-world problems.

For further information and the latest publications from our group see the plant energy website or CABiN

Back to top

 
 
null

Joshua Mylne

Associate Professor

Assoc Prof. Mylne is a new staff member hailing from UQ where he held a prestigious ARC QEII Fellowship (2008-2012) and won the Peter Goldacre Award (2012). He just accepted an ARC Future Fellowship (2013-2016) to start a new lab at UWA studying the genetic evolution of plant proteins with biomedical applications.

Plant Biology and Biochemistry

Plants have much more to offer us than solutions to our agricultural challenges. Plants provide an untapped resource of peptides and information relevant to human drugs. Our lab is asking: (i) how do plant genes evolve to create proteins with applications as drugs, (ii) how do plants process such proteins and can we manipulate this to our advantage, and (iii) can plants teach us how human drugs work, so that we can make improved or completely new pharmaceuticals? Our cross-disciplinary research provides a creative approach to drug discovery and design by dissecting plant protein evolution.

For further information see my website

Back to top

 
 
null

Matthew Piggott

Associate Professor
Synthetic Organic Chemistry, Medicinal Chemistry and Chemical Biology

Our expertise in organic and medicinal chemistry is applied to the design and synthesis of therapeutic drug candidates and small molecule probes to help investigate complex biological systems. We have several active collaborations with more biologically orientated scientists and opportunities for cross-disciplinary projects exist. The synthesis of biologically active natural products and novel aromatic molecules with potential applications in organic electronics, supramolecular chemistry, and as components of molecular machines are other areas of interest.

For further information see my staff profile

Back to top

 
 
 
null

Sam Saunders

Associate Professor
Atmospheric and Environmental Chemistry

My research interests have wide environmental implications. One of my keen interests is to measure anthropogenic impacts, to develop practical tools for environmental impact assessment. Much of my research involves the use of computer models to study atmospheric processes in detail. The models are constructed using a combination of detailed chemical mechanisms, measurements and emissions data. I have been instrumental in the development of a Master Chemical Mechanism (MCM) for use in these models. Study regions extend from local WA to wider Australia, Hong Kong, China and as far a field as the UK.

For further information see my staff profile and website

Back to top

 
 
null

Ian Small

Winthrop Professor
Organelle Gene Expression

Our group is studying the RNA world within the energy organelles of plants – the mitochondria and chloroplasts. These organelles contain the genes that code for the most important and abundant proteins on Earth, those that drive photosynthesis, the basis for most biological productivity. The regulation of the expression of these genes is crucial, yet still only poorly understood mechanistically. Our aim is to understand how the biogenesis and function of chloroplasts and mitochondria are controlled through alterations in gene expression, with the goal of making discoveries relevant to optimal use of plants in agricultural and environmental applications.

Gene regulation in plant organelles primarily occurs through changes in RNA processing, which makes these expression systems unique. Much of our research builds upon the discovery of the PPR protein family, novel sequence-specific RNA-binding proteins found in all eukaryotes, but particularly prevalent in plants (Schmitz-Linneweber and Small, Trends Plant Sci, 13, 663-670). The experiments mostly involve the model plant Arabidopsis thaliana to make use of the full range of international collections and databases on the ‘lab rat’ of the plant kingdom.

For further information see the plant energy website

Back to top

 
 
null

Steve Smith

Professor
Discovering Genes for Plant Growth

Arabidopsis thaliana provides the most powerful platform for modern genomics-based research in eukaryotes. It provides us with the opportunity to discover genes and mechanisms by which plants grow, how they produce the food that we eat, how they cope with environmental stresses (eg caused by climate change), and how they resist diseases. Research using Arabidopsis can provide training in a range of disciplines including genomics, genetics, cell biology, biochemistry, and new multi-disciplinary areas such as bioinformatics, systems biology and metabolomics.

For further information see the plant energy website

Back to top

 
 
Spackman2013

Mark Spackman

Winthrop Professor
Crystallography and Theoretical Chemistry

Group members: Simon Grabowsky and Mike Turner

Our research investigates in detail the structure of crystals, in particular the electron distribution and properties related to it, such as electric moments of molecules (dipole, quadrupole, etc.), electrostatic potential and electric field, and also measures of its response to external perturbations, including polarizability and hyperpolarizability. All research projects in this area incorporate different aspects of physical and theoretical chemistry. They utilise ab initio computational methods along with some computer programming and computer graphics and, where applicable, measurement and detailed analysis of high-resolution, low-temperature X-ray diffraction data.

For further information see my staff profile

Back to top

 
 
null

Dino Spagnoli

Dr
Computational Chemistry

My research interests involve applying computer simulation techniques to understand fundamental processes that occur at the mineral-water interface. There are many important processes that are governed by this interface. Very broadly speaking they include crystal growth, aggregation of nanoparticles, adsorption of species and pollutants to the mineral surface, and dissolution. By applying computer simulations we can gain an understanding of these processes on an atomistic scale, which can be used to guide future experiments or help understand current experimental observations.

For further information see my staff profile

Back to top

 
 
null

Scott Stewart

Associate Professor
Synthetic Chemistry

Research interests include the construction of biologically active natural products utilising modern organic synthetic methods. Many these syntheses are designed using palladium catalysed cross coupling reactions as the key step transformation. Several natural products Arboflorine (1), Pumiliotoxin B (2) and BE-26554B (3) are synthetic targets for our group because of their interesting molecular architecture and biological activity. Related to this field, methodological studies involving the improvement various reactions such as the Suzuki, Buchwald-Hartwig and intramolecular Heck reactions through the modification of nickel(0) and palladium(0) catalyts are currently being explored. Research in the discovery of novel domino transformations (the execution of two or more bond-forming transformations under identical reaction conditions) mediated by palladium are routinely carried out within the group. Medicinal chemistry interests include the synthesis of libraries of new thalidomide analogues for the inhibition of tumour necrosis factor (TNF) expression as well as determining the molecular mode of action.

For further information see my staff profile

Back to top

 
 

nullKeith Stubbs

Associate Professor
Carbohydrate Chemistry and Chemical Glycobiology

Glycobiology is the study of the structures and roles of carbohydrates in biology. Carbohydrates are present in every living system and traditionally, have been known for their role in structural integrity and as energy sources. Recently, however, carbohydrates have been shown to be involved in a variety of fundamental biological processes such as protein folding and trafficking, as well as cellular signaling and regulation. As a result glycoconjugates continue to be uncovered as important factors in health and disease. Furthermore due to their inherent chirality, carbohydrates are excellent sources of starting materials for advanced synthesis.

The laboratory headed by Dr. Stubbs is engaged in the study of:

(i) The development of chemical tools to both perturb and understand the action carbohydrate-processing enzymes which act on glycoconjugates.

(ii) Use of these chemical tools to gain new understanding as to how these enzymes and glycoconjugates mediate biological processes.

(iii) The development and use of new synthetic and chemical strategies utilising carbohydrates to address the preparation of molecules of interest.

For further information see my staff profile

Back to top

 
 

nullRobert Tuckey

Associate Professor
Molecular Steroidogenesis

Current research involves the metabolism of vitamins D2 and D3 by cytochrome P450scc, and the activation and inactivation of vitamin D by other mitochondrial-type cytochromes P450 including CYP27A1, CYP27B1 and CYP24. With collaborators we are trying to develop new forms of vitamin D which are non-toxic and have therapeutic potential for the treatment of immune disorders and cancer.

For further information see my staff profile

Back to top

 
 
 
null

Alice Vrielink

Winthrop Professor
Protein Structure by X-ray Crystallography

Group members: Anandhi Anandan

The studies in my lab focus on crystallographic analysis of a variety of proteins with the aim of using structural analysis to better understand their biology. The structural biology laboratory is well equipped with state of the art robotic crystallization equipment, X-ray diffraction equipment and computational facilities for structure solution and analysis. Cloning, expression and purification resources are also available in the laboratory in order to obtain sufficient quantities of protein for crystallographic studies. In addition we carry out kinetic and spectroscopic analyses to establish the quality of protein and pursue biochemical and biophysical studies to better correlate function with structure.

For more information see my website and staff profile

Back to top

 
 
null

Jim Whelan

Winthrop Professor
Molecular Genetics and Genomics

We use a variety of post-genomic approaches to carry out discovery based investigations concerning development and stress tolerance in plants. The main projects running in the laboratory focus on the biogenesis and function of plant mitochondria, stress responses in plants and on the role of signaling events involved in plant phosphate uptake. Both mitochondria and phosphate metabolism are key players in energy production in plants, making our investigations highly relevant for fundamental and applied research.

For further information see the Plant Energy website
Back to top

 
 
null

Duncan Wild

Dr
Laser Spectroscopy & Computational Chemistry

Our work is aimed towards finding a deeper understanding of how molecules interact with one another. This has a profound impact in the areas of chemical reactivity, dissolution of species in solution, and even in furthering our understanding of the shapes and behaviours of biological macromolecules such as proteins. We are able to experimentally observe the complexes formed between individual molecules that are tethered together via intermolecular interactions such as hydrogen bonding. We use laser spectroscopy to ‘shine a light’ on the structures and binding energies for the complexes and back it up with high level computational chemistry.

For further information see my website and staff profile

Back to top

 
 
null

Michael Wise

Professor
Bioinformatics and Computational Biology

Research in the Bioinformatics and Computation Biology Lab. boils down to the application of computational techniques to investigate biological questions. Current application domains include:

  • Bioinformatics of anhydrobiosis (species’ ability to survive with minimal water)
  • Microbial bioinformatics
  • Low complexity/natively unfolded proteins
  • Computational evolutionary biology

For further information see my staff profile

Back to top

 
 
null

George Yeoh

Winthrop Professor
Liver Research

Group members: Roslyn London, Caryn Elsegood, and Ken Woo

Our research group focuses on the biology of the liver progenitor cell (LPC) called an “oval cell” which describes its shape. We envisage an enormous potential for this cell as the vehicle for cell and gene therapy to treat liver disease. We contend it is superior to other cell types such as the hepatocyte and the embryonic (ESC) or adult stem cell (ASC) for many reasons. In particular, it is robust and simple to freeze and store, then thaw and grow by in vitro culture when required. It can be differentiated into either hepatocytes or cholangiocytes (bile duct cells) quite easily and rapidly when maintained under appropriate conditions, therefore it is more versatile than the hepatocyte. Most importantly, the LPC is developmentally close to the hepatocyte and the cholangiocyte in contrast to the ESC or ASC, which will require many more steps and much coaxing to produce useful cells for liver therapy. Our long-term vision is to hasten the day when human LPCs are utilised to treat liver disease, especially end-stage liver disease for which currently organ transplant is the only solution. A realistic expectation in the short term is to use LPCs to “bridge” patients thereby extend their survival and enhance their probability of finding a suitable organ donor. A more ambitious and longer-term aim is to use these cells to circumvent the requirement for organ transplant, particularly in less severe liver diseases.

To utilise LPCs we must identify and understand the action of growth factors and cytokines, which influence them. To accomplish this, we have characterised the pattern of cytokine expression in two mouse model of liver disease in which LPCs are involved in repairing the liver.These studies indicate that a subset of inflammatory cells, the macrophages and cytokines they produce namely TNF alpha and TNF like weak inducer of apoptosis (TWEAK) are the major LPC regulators. To understand both the cellular and molecular mechanism of action mediated by inflammatory cells we are using cultures of LPCs and LPC lines. This knowledge can be used to increase their contribution to liver regeneration in vivo which can lead to positive outcomes for liver disease patients. Both in vivo and in vitro, extended growth of some LPC lines result in transformation to cancer; in this context hepatocellular carcinoma. Therefore it is important to document changes in gene expression that are responsible for transformation.

For further information see my staff profile

Back to top