2014 cbms mres final - macquarie university
TRANSCRIPT
MRes RESEARCH
in the DEPARTMENT OF CHEMISTRY & BIOMOLECULAR SCIENCES
This booklet outlines research projects available with staff of the Department of Chemistry & Biomolecular Sciences, Macquarie University for 2014. The booklet will introduce you to the Department and help you identify research projects that interest you. In the MRes program CBMS students will work under the supervision of one or more academic staff, as they progress towards completing their degree. In year one of the program CBMS students will undertake two separate five week research experience projects to gain familiarity with research areas of interest. In year two they will select a topic and conduct research and report these results in the form of a written thesis.
You are free to choose to select any project on offer in this booklet, provided that facilities and research supervisor are available. Clearly, the outlines here are very brief and general, so you should contact staff offering projects that interest you in and discuss your options further. There is often scope for modifying a project to take advantage of your particular skills and interests.
Members of the MRes Committee are always available to assist students, particularly those from other institutions, in finding a suitable project amongst CBMS research activities.
Members of the CBMS MRes Committee for 2014: Dr Louise Brown Assoc. Professor Bridget Mabbutt (convenor) Assoc. Professor Mark Molloy Assoc. Professor Andrew Try
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Plasma Protein and Peptide Biomarkers (of Colorectal Cancer)
Colorectal cancer (CRC) is the second most common malignancy by incidence and cause of death in the Western world. CRC is the most common registrable cancer in Australia with 13,000 new cases resulting in 13.1% (♂12.7%, ♀13.5% of the total 4,000) of all Australian cancer deaths. Human blood plasma continues to be our most available biomarker fluid because it is easily available and it comprehensively samples the human condition in all states of health and disease. This project elucidates the normal and diseased human plasma proteome (in great depth) and peptidome in order to discover novel prognostic/diagnostic markers of cancer onset, staging and recurrence. Unfortunately, like many protein-rich biofluids (e.g., serum, plasma, saliva, tears and urine) plasma has an extraordinary protein concentration range – some say as high as 13 logs. Great discovery opportunities exist if one can "drill more deeply". This project is based upon new technologies developed and patented here at Macquarie University.
Selected Publications
1. Saldanha RG, Molloy MP, Bdeir K, Cines DB, Song X, Uitto PM, Weinreb PH, Violette SM, Baker MS. Proteomic Identification of Lynchpin Urokinase Plasminogen Activator Receptor Protein Interactions Associated with Epithelial Cancer Malignancy. J Proteome Res. 2007 6(3): 1016-1028. [IF= 5.113]
2. McKay MJ, Sherman J, Laver MT, Baker MS, Clarke SJ, Molloy MP, The Development of Multiple Reaction Monitoring Assays for Liver Derived Plasma Proteins. Proteomics (Clin Apps), 1 (12), 1570-1581, 2007 [IF= 6.1].
3. Lee, A, Kolarich D, Haynes PA, Packer, NH, Baker, MS. Liver Membrane Proteome Glycosylation Changes in Mice Bearing an Extra-hepatic Tumor. Mol. Cell Proteomics, Sep;10(9): M900538MCP200, 2011. [IF = 8.8].
4. Randall SA, McKay MJ, Baker MS, Molloy MP. Evaluation of blood collection tubes using selected reaction monitoring MS: implications for proteomic biomarker studies. Proteomics. 2010; 10(10), 2050-6 (Erratum issued August 15th, 2011) [IF=4.2].
5. Jankova L, Chan C, Fung CL, Song X, Kwun SY, Cowley M, Kaplan W, Dent OF, Bokey L, Chapuis PH, Baker MS, Robertson GR, Clarke SJ, Molloy MP. Proteomic comparison of colorectal tumours and non-neoplastic mucosa from paired patient samples using iTRAQ mass spectrometry, Mol. BioSyst., 2011, 7, 2997–3005.
6. Lee LY, Hincapie M, Packer N, Baker MS, Fanayan S, Hancock WS. Optimization of native multi-lectin affinity chromatography for enrichment of glycoproteins from MCF 7 total protein lysate, J Sep Sci. 2012 Sep;35(18):2445-52. doi: 10.1002/jssc. 201200049. [IF=2.6].
7. Tan S-H, Kapur A, Abidali M, Baker MS. A Novel Human Plasma Ultradepletion Strategy. J Proteome Res. in press Oct 22nd 2012. Manuscript ID: pr-2012-007182.R1. [IF=5.1].
8. Fanayan S, Smith JT, Sethi MK, Cantor D, Goode R, Baker MS, Hancock WS, Nice E. Chromosome 7-centric analysis of proteomics data from a panel of human colon carcinoma cell lines, J Proteome Res., in press, accepted December 10th, 2012. [IF = 5.1].
9. O’Neil SE, Palviainen MJ, ten Have S, Filiou M, Gonzalez A, Hodge K, Surinova S, Penque D, Baker MS. Clinical proteomics stretch goals: EuPA2012 roundtable report. J. Proteomics, accepted April 10th 2013.
10. Cantor D, Slapetova I, Kan A, McQuade LR and Baker MS Overexpression of αvβ6 integrin alters the colorectal cancer cell proteome in favour of elevated proliferation and a switching in cellular adhesion which increases invasion. J Proteome Res., accepted May 13th 2013. [IF = 5.1].
11. Manveen K. Sethi MK, Thaysen-Andersen M, Smith JT, Baker MS, Packer NH, Hancock WS, Fanayan S. Comparative N-glycan profiling of colorectal cancer cell lines LIM1215, LIM1899 and LIM2405 reveals unique bisecting GlcNAc and α2,3-linked sialic acid determinants carried by membrane proteins of metastatic and aggressive cell lines. Mol. Cell Proteomics. Submitted August 2013.
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major causes of blindness. There is no way to prevent cataract and no 'cure' other than surgical removal of the lens. Elucidation of the mechanism of ARN cataract is an essential first step in the development of a preventative and/or therapeutic treatment for this disease. The human lens contains a number of low molecular weight compounds, known as UV filters (see [1] – [3]). We have shown that these UV filters covalently bind to crystallins, causing modifications similar to those observed in ARN cataract. Furthermore, when the UV filter-crystallin adducts are exposed to UV light of levels normally experienced by the lens, protein damage is accentuated. Research projects are available on further examining the effect of UV light and metals normally present in the lens on UV filters bound to lens proteins. This will include determining the photo- oxidative products and their mechanism of formation, and comparing these products to those observed in human cataractous lenses to identify important biomarkers. Research projects are also available on examining the biosynthesis and reactivity of novel UV filters we have recently identified and their possible roles in human lens damage. Our research is also starting to focus on other modifications observed over time to long-lived proteins, including the crystallins, and their roles in aging, and projects are available related to this. Ethnopharmacological Study of Medicinal Plants (Ranganathan, Vemulpad)
Research projects aimed at working with Indigenous people to isolate and identify novel bioactive compounds from traditional Indigenous medicines are available. Approximately 25% of all pharmaceutical products worldwide have originated from traditional medicinal knowledge and the study of this knowledge is of key importance in the discovery of new drugs. Plants that have been used traditionally by Indigenous people to treat bacterial or fungal infections or cancers are the main focus of our research. Through research partnerships we have established with Australian Aboriginal elders and Indian elder custodians of traditional knowledge, we have identified a range of medicinal plants with strong antimicrobial and anticancer activities. Projects are available to undertake bioassay-guided fractionation of plant extracts using assays and chromatographic methods to isolate the most bioactive compounds. Structures of the pure compounds will be elucidated by spectroscopic methods (eg NMR, MS, UV). In order to preserve the traditional knowledge of Indigenous people and provide information that can be used for their cultural and educational purposes as well as a resource for the wider scientific community, we are also developing bioinformatics databases to integrate, visualise and analyse both first hand and public domain traditional medical plant data. An opportunity to participate in a benefit sharing and capacity building educational program will also be available as part of this research. Selected Publications
1. Austin CJD, et al. Mutation of Cysteine Residues Alters the Heme-Binding Pocket of Indoleamine 2,3-dioxygenase-1. Biochemical & Biophysical Research Communications, 2013, 436, 595-600.
2. Bridewell, DJA, et al. Natural Product-Inspired Pyranonaphthoquinone Inhibitors of Indoleamine 2,3-Dioxygenase-1 (IDO-1). Australian Journal of Chemistry, 2013, 66, 40-49.
3. Smith JR, et al. Novel Indoleamine 2,3-Dioxygenase-1 Inhibitors from a Multistep In Silico Screen. Bioorganic & Medicinal Chemistry, 2012, 20, 1354-1363.
4. Packer J, et al. Medicinal Plants of New South Wales (NSW), Australia. In: Singh RJ, ed. Genetic Resources, Chromosome Engineering, and Crop Improvement Series: Medicinal Crops Vol. 6: CRC Press, 2012, 257-294.
5. Packer J, et al. An Ethnobotanical Study of Medicinal Plants Used by the Yaegl Aboriginal Community in Northern New South Wales, Australia. Journal of Ethnopharmacology, 2012, 138, 244-255.
6. Lyons B, et al. Age-Dependent Modification of Proteins: N-Terminal Racemization. FEBS, 2013, 280, 1980-1990. 7. Truscott, R JW, et al. Is Protein Methylation in the Human Lens a Result of Non-Enzymatic Methylation by S-
Adenosylmethionine. Experimental Eye Research, 2012, 99, 48-54. 8. Mizdrak, J., et al. Tryptophan-Derived Ultraviolet Filter Compounds Covalently Bound to Lens Proteins are
Photosensitizers of Oxidative Damage Free Radical Biology & Medicine, 2008, 44, 1108-1119. 9. Mizdrak J, et al. Novel Human Lens Metabolites From Normal Cataractous Human Lenses, Tetrahedron, 2007, 63,
4990-4999.
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Publicationanna, S. Ranga
Dev. Res., 2011,cko, S. Rangann, compared to hRobinson, R. Moteomic analysted with invasi
kwad, V. Khanpe for integrarmatics, 2008,
α-D-mannosunctional pro
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organize Alate the locat
ns anathan “Molec 27, 74-84
nathan “Comprehuman and mou
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nna, S. Vemulpating Australia9, Suppl 12, S2
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alton, S. Rangane helminth pathmalian host” M
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sis of alternativ0, Suppl 1, S5. nathan “An intehogen, Fasciol
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in Chemoinform
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PublicationQ. M.; Mahonier reagents” TeD.; Oukhatar, Fllanon, M. M.;s” Bioorg. MedQ. M.; Ijaz, S.’s base analogun, M. D. H.; Zh’s base analoguhi, M.; Zhu, Ks containing at ln, M. D. H.; M-functionalised , A. B.; Craig, straps” Synthes
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d. Chem. Lett. 2; Craig, D. C.es” Tetrahedrohu, K.-X.; Jenses” Eur. J. Org
K.-X.; Jensen, Pleast one halogeMahon, A. B.;Tröger’s base aD. C.; Try, A
sis 2009, 636-6C.; Klepetko, J551.
tp://www.cbm
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g, D. C. Try,11, 8509-8514.B.; Try, A. C.“Proflavine der
2011, 2203-2206Try, A. C. “Sy
on 2011, 5798-5sen, P.; Try, A.g. Chem. 2010, P.; Craig, D. Cen” Eur. J. Org; Jensen, P.; Canalogues” Eur
A. C. “A new c642. J.; Turner, P. “
ms.mq.edu.a
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C.; Try, A. C. “g. Chem. 2009, 4Clegg, J. K.; T. J. Org. Chem.lass of Tröger’
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on of Tröger’s
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Plant hormone involvement in chlorophyll synthesis The ChlH subunit of magnesium chelatase has reported to be a plant hormone receptor. Our recent experiments indicate that this may only occur after posttranslational modification. This project aims to confirm this finding and characterise the hormone binding.
Chlorophyll d synthesis by A.marinus We have identified a putative chlorophyll d synthase (see JBC article below). We aim to introduce this enzyme into plants and other cyanobacteria which do not make chlorophyll d. This may improve the photosynthetic capacity and allow these organisms to grow more efficiently under low light
Analysis of chlorophyll f containing organism isolated from stromatolites We have a partial genome sequence of this organism and have a pure culture of this organism. There are numerous projects available on this novel organism (see Science article below). Come and talk to me about it.
Selected Publications 1. Schliep M., Crossett B., Willows R. D., Chen M. “18O-Labelling of chlorophyll d in Acaryochloris
marina reveal chlorophyll a and molecular oxygen are precursors” J. Biol. Chem. 2010, 285 (37), 28450-28456.
2. Chen, Min, Schliep, Martin, Willows, Robert D, Cai, Zheng-Li, Neilan, Brett A, Scheer, Hugo “A Red- Shifted Chlorophyll” Science, 2010, 329 (5997), 1318-1319.
3. Lundqvist J., Elmlund H., Peterson Wulff R., Berglund L., Elmlund D., Emanuelsson C., Hebert H., Willows R.D., Hansson M., Lindahl M. and Al-Karadaghi S. “ATP-induced conformational dynamics in the AAA+ motor unit of magnesium chelatase” Structure, 2010, 18, 354-365.
4. Meinecke L., Alawady A., Schroda M., Willows R. D., Kobayashi M.C., Niyogi K.K., Grimm B., and Beck C. F. “Chlorophyll-deficient mutants of Chlamydomonas reinhardtii that accumulate magnesium protoporphyrin IX” Plant Molecular Biology, 2010, 72 (6), 643-658.
5. Jerkovic A., Kriegel A. M., Bradner J. R., Atwell B. J., Roberts T. H., Willows R. D. “Strategic distribution of protective proteins within bran layers of wheat (Triticum aestivum L.) protects the nutrient-rich endosperm” Plant Physiol., 2010, 152, 1459-1470.
http://www.chem.mq.edu.au/
Department of Chemistry and Biomolecular Sciences
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In immunosensor development, we will apply it to the detection of a real-life analyte (e.g. cortisol, tumour marker), while the DNA biosensor will be used to study the interaction between DNA and selected drugs of medical significance. Graduates with familiarity in analytical techniques are of demand in the current employment market. Note that a background in biology is not required but willingness to acquire new bioanalytical skills will be essential.
Probing Environmental Chemistry using Electroanalytical Techniques Determination of copper speciation in natural waters or manganese speciation in drinking waters Copper is a highly toxic trace metal present at elevated concentration in many natural waters. The toxicity of copper is dependent on its physicochemical form (speciation) with inorganic species such as ionic copper being the most toxic. Copper speciation can be determined using electrochemical methods including different forms of stripping voltammetry. However, there have been surprisingly few direct comparisons of these methods on natural water samples and it is difficult to determine the best method for use in metal bioavailability studies. In this project, various electrochemical procedures for the determination of copper speciation will be set up and compared on a range of copper-contaminated natural water samples. The copper toxicity of these samples will also be assessed using a highly sensitive bacterial bioassay. The relationship between copper speciation and bacterial toxicity will be investigated. In this project, a speciation study of manganese using electrochemical methods will be conducted to address concerns about the taste of some drinking water samples collected from Canberra suspected to have arisen from the presence of manganese species in the water samples. Note these projects will be of interest to students with an interest in trace metal bioavailability / environmental chemistry.
Determination of Cr(VI) in natural waters Chromium is a toxic trace element present at part per billion (ppb) concentrations in natural waters. The toxicity of chromium varies with its oxidation state. For example, Cr(VI) is known to be far more toxic than Cr(III). In order to effectively protect aquatic ecosystems from the effects of anthropogenically-derived chromium inputs, it is therefore necessary to not only determine total chromium concentrations, but also the oxidation states. The determination of Cr(VI) at low ppb concentrations is surprisingly challenging. Most methods require the preconcentration of Cr(VI) through coprecipitation with iron hydroxide before measurement by colorimetry or some form of atomic spectroscopy. In this project, we will examine the potential of several electrochemical methods for the determination of Cr(VI) at low ppb concentrations. Methods will include square wave voltammetry and cathodic stripping voltammetry. The developed method will be compared against existing non- electrochemical methods for Cr(VI) determination on a range of natural water samples. This project will be of interest to students with an interest in method development and the monitoring of toxic trace metals in natural waters.
Electro-remediation of polluted textile effluents Azo dyes are commonly used in the textile and carpet dyeing industries. Very often, enormous quantities of dye containing wastewaters are being released into effluent streams. Such dyes are harmful to aquatic fauna and flora as well as humans. In this project, electrochemical removal and/or treatment of azo dyes in textile effluents will be explored. This will be achieved using the conducting polymer, polypyrrole, or its derivatives. A distinct advantage of this method is that dye molecules are entrapped in the polymer film for removal, rather than being chemically treated that generates even more harmful products as exhibited by many other treatment methods. Apart from electrochemistry, students will also engage in polymer chemistry, materials chemistry and environmental chemistry in this project. These projects will provide an opportunity for students to gain experience with a range of analytical techniques, as well as that in method validation and quality assurance. Graduates equipped with all these skills are always of demand in the current employment market.
www.cbms.mq.edu.au/academics/dwong.html