Honours in Biochemistry/Biotechnology/Chemistry
Projects on offer for 2006 - projects may be withdrawn at any time.
Contact the staff member for more details of projects.
Nanostructured multicomponent biodegradable polymeric materials
A/Prof Qipeng Guo
Biodegradable polymers have been widely used for many biomedical and biotechnological applications, including as surgical materials in clinics, as drug-delivery systems in the pharmaceutical industry, and as scaffolds in tissue engineering. This project will develop nanostructured multicomponent polymeric biomaterials based on biodegradable polymers. The multicomponent polymeric biomaterials to be developed will combine the advantages of the individual component polymers and exhibit well-controlled nanostructure, excellent properties, required biocompatibility and desired biodegradability for biomedical and biotechnological applications.
A stipend of $5,000 may be available for this project. For further information contact: A/Prof Qipeng Guo (qguo@swin.edu.au).
Polymeric biomaterials for tissue engineering applications
A/Prof Qipeng Guo and Tony Barton
Biomaterials are those which are designed to restore, augment, or replace the natural functions of the living tissues or organs in the body. This research aims to develop new polymeric biomaterials which are both biocompatible and biodegradable. The project will involve design, preparation and characterization of a series of novel polymeric biomaterials. Cell culture experiment will be performed with these new polymeric biomaterials to evaluate their potential applications in tissue engineering.
A stipend of $5,000 may be available for this project. For further information contact: A/Prof Qipeng Guo (qguo@swin.edu.au).
The rational design of compounds to bind to GABA-T.
Margaret Wong
Gamma-aminobutyric transferase (GABA-T) is a major enzyme involved in the breakdown of gamma-aminobutyric acid (GABA) in the brain.This is a major inhibitory neurotransmitter in the brain and abnormalities in its levels can have serious neurological effects such as epilepsy. The tertiary structure of this enzyme is now known. This will form a basis for the rational design of compounds to modulate the activity of this enzyme.
Rotavirus Capsid Proteins
Margaret Wong and Enzo Palombo
The human rotavirus causes lots of ghastly gastric upsets and worse. However there is currently no effective drugs for the treatment of a rotavirus infection. Molecular modelling studies of the viral capsid proteins are needed to obtain realistic structures which can be used as a basis for drug design.
Design of Glutathione S-transferase inhibitors
Margaret Wong
Glutathione S-transferase is a very important enzyme for removing toxic compounds from the body. It also removes drugs such as those used in cancer therapy.Inhibitors have the potential for extending the therapeutically useful life of some anticancer drugs. Many crystal structures are available of GST's and can be used as a basis for design.
Molecular Modelling of Severe Acute Respiratory Syndrome (SARS)
Margaret Wong
SARS is caused by a virus with no close relationship to any other known virus. The sequence of several proteins within this virus have recently been elucidated and one protein has been crystallised. It is proposed to develop 3-D models of targetted SARS proteins, using molecular modelling techniques, with the long term goal of developing compounds which can modify the activity of the virus, with the potential of being drugs against this virus.
The development of small molecule analogues to an economically important cyclic plant toxin.
Margaret Wong in collaboration with Linfa Wang, CSIRO Livestock Industries, Australian Animal Health Laboratory
Scientists at CSIRO have recently identified several peptides, which bind to a monoclonal antibody raised against a small cyclic plant toxin molecule. As such these peptides offer the potential for use as an antidote to poisoning by various plants. Some of these peptides contain two Cys residues that could also potentially form a ring. Are they mimics of the plant toxin? Molecular modelling studies will determine whether this ring structure is the active conformation. Small non-peptidic molecules will be developed to mimic the active conformation.
The development of compounds for the treatment of bipolar disorder
Margaret Wong
Bipolar disorder, formerly known as manic depression, is as serious a disorder as schizophrenia, and as life threatening. Recent research seems to indicate a common genetic origin with schizophrenia. Several different enzymes have recently been proposed as being involved directly with this disorder and it is proposed to study the 3-D characteristics of these enzymes to determine whether they are suitable to use for drug design.
Molecular Modelling of Cyclophilin related proteins in wheat
Margaret Wong and Mrinal Bhave
Cyclophilins are a class of enzymes usually involved in the trans-cis isomerization of peptide bonds. Rather surprisingly some sequence related proteins have been found in wheat endosperm though what they are doing there and why has yet to be determined.The genes for these proteins colocalise with those of various storage proteins so they may influence wheat quality.Molecular modelling to create a three dimensional structure for these proteins may provide some leads to their activity.
Bioactivity of traditional medicinal plants
Dr Enzo Palombo, Assoc Prof Ian Harding, Dr Sylvia Urban (Marine and Terrestrial Natural Product Chemistry Group, RMIT University)
Medicinal plants and herbs have been used as treatments for numerous human diseases for thousands of years. The natural products derived from such plants have proven to be an abundant source of biologically active compounds, many of which have been the basis for new pharmaceuticals. Ayurvedic medicine relates to the ancient healing traditions that derived in India over 5000 years ago. It is one of the major traditional medicinal systems of the world, second only to Chinese medicine. However, it has influenced and been combined into other major traditional medical systems, such as Chinese, Pakistani and Tibetan medicine. Ayurvedic medicine is of interest to medical practitioners, scientists and the general public for several reasons. First, Ayurvedic suppliers are becoming a major part of the nutriceutical industry, providing concentrated extracts or isolated components from major Ayurvedic herbs. Second, the modern emphasis on scientific evaluation of traditional remedies means that there is increasing desire to use "proven" substances that have been validated by modern scientific methods. Third, plant extracts may contain novel bioactive compounds that can be developed into new therapeutic agents.
This project will involve a scientific investigation of Ayurvedic plant medicines to determine if scientific examination supports their traditional use, and will focus on plants that have purported anti-microbial activity. Plants will be collected from commercial suppliers and extracts will be prepared using organic solvents of different polarities. Extracts will be concentrated and tested against a number of bacteria (Gram positive, Gram negative and Mycobacteria), fungi and viruses. Once activity is validated, extracts will be chemically separated using chromatography columns and HPLC, and fractions will be tested for bioactivity. Isolated compounds will be further characterized using IR, UV, mass spectrometry and NMR spectroscopy. In this way, novel chemicals may be identified that could be developed into new pharmaceutical lead compounds. Another aspect of the study will be to examine plants collected during different seasons or from different altitudes to determine if environmental conditions influence the synthesis of bioactive compounds.
Investigating the synergistic effects between phytochemicals and antibiotics
Dr Enzo Palombo
Antibiotic resistance is one of the major problems of modern medicine. Using plant-derived chemicals (phytochemicals) in combination with antibiotics is considered a way of enhancing the activity of antibiotics (synergism) and therefore extending the useful lifetime of these drugs. In this project, the interactions between phytochemicals with antibacterial activity (crude plants extracts, essential oils and purified chemicals) and common antibiotics will be investigated. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of antibiotics against common bacteria will be calculated in the absence and presence of plant extracts. Synergistic, antagonistic or indifferent relationships between extracts and antibiotics will be determined. Phytochemicals with synergistic potential will be further characterised biochemically or by using time-kill growth assays to investigate the effect on target bacteria.
Biologically Active Compounds from Marine Bacteria
E. Ivanova, E. Palombo
Marine bacteria comprise numerous clusters of prokaryotic organisms that are widely distributed in the marine environment. Coexistence and survival in such environments was a reason for the evolutionary development of the diverse metabolic pathways observed in marine bacteria following the production of biologically active metabolites. Intensive studies of these organisms have demonstrated their capability to produce enzymes, antibiotics, cytotoxins, antibactericidal, bacteriolytic, autotoxic, antifouling and biocontrol compounds active against invertebrate larvae, algal spores, fungi, and diatoms (Austin, 1989; Jensen, Fenical, 1994; Holmström, Kjelleberg, 1999).
This project aims to screen a collection of 100 marine bacteria for antibacterial, auto-inhibitory, and anti-viral compound production mainly focusing on low molecular weight substances with antimicrobial activity and surface active properties.
The study of the nature of haemolysins produced by P. issachenkonii and the elucidation of their mechanism of action against red blood cell
E. Ivanova, E. Palombo
Recently we described the symbiotrophic association of marine aerobic gamma-Proteobacteria that are able to degrade the thallus of brown algae Fucus evanescens (Ivanova et al. 2002a). It was found that P. issachenkonii KMM 3549T produces a range of biologically active substances and that the synergetic effect of these gives a strong advantage against competitors during colonization of algal thallus. This project is aimed to evaluate the production and possibly chemical structure of haemolysins by P. issachenkonii
Analysis of genes involved in determining wheat grain quality.
M. Bhave
General description of the area: Wheat is the most widely consumed cereal grain worldwide and the major crop of Australia. The mature wheat grain is composed of 12-14% protein, the rest being mostly starch. The protein content largely determines the nutritional quality, while the proportion, composition and properties of starch, together with the proteins, determine the end-product applications of the grain. There are distinct differences in the wheat lines in relation to these properties. The protein and starch are not distributed randomly in the grain; rather, they form structured protein bodies and starch granules, respectively. Wheat genetics is rather complex, wheat being a polyploid, and the genetic basis of grain quality involves several key gene families (see below). This area of research investigates genes involved in regulating storage protein folding and starch composition. Various individual research projects can be taken up to investigate the following gene families:
(i) analysis of the GSP-1 (grain softness protein-1) gene in landraces of wheat;
(ii) analysis of the puroindoline a and b in synthetic wheats;
(iii) variations in the cyclophilins, belonging to a number of classes;
(iv) analysis of the many different aquaporin genes
(v) variations in the ‘waxy’ proteins in the landraces and synthetic wheats.
(vi) expression and analysis of proteins encoded by select genes (co-supervisor Tony Barton)
Genetic systems encoding heavy metal resistance and/or transport in bacteria and their applications in environmental biotechnology
Mrinal Bhave and Enzo Palombo
While heavy metals are generally toxic to cells, certain soil bacteria that are exposed to heavy metal contaminants do not suffer the biological effects of metal toxicity. This is due to their having developed, or acquired, genetic systems that allow them to survive in such environments. The nature of genetic systems involved, the mechanisms of regulation of these genes, and the biochemical mechanisms of resistance vary greatly for the different metal ions and in different bacterial genera and species. Some of these genetic systems are being utilized worldwide for developing biotechnological applications such as bioremediation, biosensors or biosorption of heavy metals. This project will investigate the genetic and physiological/biochemical basis of heavy metal resistance in bacteria and develop applications such as biosensor systems, bioremediation systems, biofilms or other types of biosorbents of heavy metals.
Projects in collaboration with the Royal Botanic Gardens Melbourne:
Mrinal Bhave Co-supervisor: Liz James or Rob Cross
A number of collaborative projects involving microbiology, conservation genetics or horticultural research are possible. Please discuss with M. Bhave.
Cloning and Expression of a Telomerase
Tony Barton
All somatic cells have a limited number of cell divisions due to a progressive shortening of the telomeres at the ends of chromosomes and the inability of somatic cells to maintain telomere length is attributed to an absence of active telomerase.
As part of a larger project to restore the growth potential of cells in culture for tissue engineering this project will express in baculovirus an telomerase.
The h-TERT (telomerase) gene has been obtained and will be cloned into an appropriate baculovirus transfer vectors. A his-tagged contruct has already been constructed to facilitate purification for the purposes of raising antibodies to the protein and recombinant baculovirus have been constructed but expression of the telomerase protein has not been verified. Truncated versions or sub-domains may need to be constructed.
Techniques: PCR, cloning, cell culture, viral isolation, gel electrophoresis, western blotting, protein purification..
Testing of a Chitinase knockout Baculovirus
Tony Barton
The baculovirus-insect cell expression system is one of the most efficient for producing large multi-domain eukaryote proteins. However, levels of secreted recombinant protein produced by baculovirus are often disappointing. It has been suggested that competition for the secretory pathway with endogenous viral proteins may reduce the efficiency of secretion. One protein that is redundant for passage of virus on insect cells is the viral encoded chitinase, which has been shown to enter the endoplasmic reticulum. A previous project made a "knockout" virus lacking chitinase. This project has as its aim the testing of this chitinase "knockout" virus for secretion efficiency of recombinant proteins. Construction of transfer vectors with genes with secretory signal sequences will carried out and homologous recombination will be used to target the sequences to a novel locus of baculovirus. Comparison of expression levels will be made with parallel standard virus constructs or with preexisting recombinant viruses.
Novel Microbial Biocatalysts
Michael Zachariou
CSIRO has developed a microbial and enzyme discovery technology known as the Evolver Technology. It has so far been used to discovery 100's of microbes and enzymes with unique phenotypic character some of which are not found on any database and are therefore thought to be new microbes. With this technology, CSIRO has also been able to use these biocatalysts to perform unique chemical reactions such as hydroxylation reactions that are difficult to carry out synthetically. Through this Honours project, CSIRO now wish to use this technology for discovering biocatalysts that can bioremediate recalcitrant pollutants such as some textile dyes and herbicides. The project will involve applying evolutionary and mutagenesis approaches to the Evolver Technology in order to evaluate the various approaches for their ability to select the optimal biocatalytic candidate for the bioremediation of a recalcitrant pollutant. The project will be carried out at CSIRO's Division of Molecular and Health Technologies in Clayton (Monash University site).
 Abstracts of 2005 projects
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