Undergraduate and Postgraduate Opportunities

Primary Supervisor Contact: Prof. Janice R. Aldrich-Wright, j.aldrich-wright@westernsydney.edu.au

Co-Supervisors:

Would suit students interested in: Synthetic Chemistry

Various structural conformations of DNA other than B-DNA, such as cruciform, intramolecular triplexes, slipped-strand, parallel-stranded and unpaired DNA structures and quadruplex DNA (QDNA), exist and have been shown to be vital in several cellular processes including replication, gene expression, growth, recombination and repair. G-quadruplex motifs have been identified in key regulatory regions of the human genome, such as promotors, gene bodies, untranslated regions and more importantly as telomeres located at the ends of chromosomal DNA. Telomeres protect chromosomal DNA during replication and repair processes and play an essential role in cellular proliferation and cell death. G-quadruplex motifs can fold into various topologies. In normal cell during replication, non-coding telomeres are removed with each replicative cycle, leading to the successive shortening, at a critical length, cell death is triggered. In cancer cells death is avoided by an overexpression of telomerase which repairs the telomeres so that they are not progressively shortened during replication, effectively rendering the cell line immortal. If G-quadruplex sequences are stabilised, telomerase activity is inhibited, preventing the replication of cancer cells. Platinum complexes that selectively stabilise and bind strongly to QDNA topologies and also exhibit anticancer activity have been the focus of recent research in the laboratory of Aldrich-Wright at Western Sydney University. Based upon our previous results this project will design, synthesise and characterise effective G-quadruplex stabilisers that incorporate planar aromatic surfaces to increase the stacking interactions such as symmetrical [Pt(1,10-phenanthroline)₂] and [Pt(tetramethyl-1,10-phenanthroline)₂] to exhibit strong G-quadruplex affinity as well as cytotoxicity in human cancer cell lines. Asymmetrical and dinuclear structures are also to be synthesised to explore their potential as QDNA stabilisers. Each resulting metal complex will be characterised using NMR, HPLC, MS and UV-Vis. Following characterisation, mass spectrometry binding assays and cell line trials will be undertaken. By using these techniques, this project aimed to investigate G-quadruplex platinum complex interactions, leading to the contribution towards the development of the next generation of anticancer complexes.

Primary Supervisor Contact: Prof. Janice R. Aldrich-Wright, j.aldrich-wright@westernsydney.edu.au

Co-Supervisors:

Would suit students interested in: Synthetic Chemistry

Cancer accounts for 8 million deaths each year and that number projected to rise by 70% over the next two decades.¹ The most well-known conventional platinum anticancer complex is cis-diamminedichloroplatinum (cisplatin) which effectively treats testicular, ovarian, head, neck and small-cell lung cancer.^2,3 Vomiting (emetogenesis), hearing loss (ototoxicity), kidney damage (nephrotoxicity) and nervous system (neurotoxicity) damage are often the characteristic side effects of treatment^.4-5 Acquired resistance is frequently a consequence of sub-toxic accumulation inside the cell, due in part to reduced drug influx and increased drug efflux.⁶ Resistance in cancer cells is enhanced by the repair/tolerance to DNA-cisplatin adducts, modulation of the pathways that control regulated cell death, loss of function of upregulated sequence-specific binding factors, such as proteins, and an increased concentration of glutathione and metallothioneins.^7-9 The clinical limitations of cisplatin have been the motivation for the creation of thousands of cisplatin analogues, resulting in complexes that employ the same mechanism of action where the platinum coordinately binds to DNA. Many researchers are striving to create effective inorganic complexes that exhibit anticancer activity. The intrinsic challenges of chemotherapy demand that new strategies utilising different mechanisms of action to interrupt the cellular machinery of cancer cells be developed.¹⁰ Current anticancer compounds interact with in both cancerous and normal cells however researchers aspire to create more potent platinum complexes with increased cytotoxicity which target cancer cells more effectively and will result in a better prognosis. Our groups strategy is to utilise unconventional platinum complexes different mechanism that induces cytotoxicity in cancerous cells. The complex incorporates coordinated polyromantic ligands (P_L) and ancillary ligand (A_L) to form [Pt(P_L)(A_L)]^2+. Unlike cisplatin this complex cannot covalently bind to DNA. The mechanism for this interaction is not fully understood, however for [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane) platinum(II)] dichloride (56MESS) it is up to 100 times more active than cisplatin in a variety of cell lines, with an IC₅₀ of 0.009 ± 0.002 μM in the L1210 murine leukaemia cell line.¹¹ Increased cytotoxicity reduces the dosage required, treatment time and the reducing the chance of acquired resistance. Although the in vitro activity of these complexes is exceptional, in vivo activity has been disappointing due to poor pharmacokinetics.

The design strategy being explored here is to form platinum(IV) complexes where the two additional axial ligands can be coordinated to either a targeting molecule or a bioactive ligand. The development of Pt(IV) prodrugs is an increasing attractive field as Pt(IV) complexes have many advantages over Pt(II) in vivo. Platinum(IV) complexes are more kinetically inert than the parent platinum(II) complexes, which can be administered orally.^12-13 Once inside cancer cells, platinum(IV) complexes undergo activation by a two-electron reduction that produces a simultaneous release of the parent cytotoxic platinum(II) drug as well as the two axial ligands.¹⁴ Recently we reported upon several such compounds with valproate (VPA) and phenylbutyrate (PhB), which alter gene transcription that effects arrest, differentiation, apoptosis, and inhibition of tumor angiogenesis.^15,16 The resulting complexes Inhibition was demonstrated for cct-[Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(R₁)(R₂)]²⁺ (here R₁ and R₂ are PhB, shown in Figure) ~15 times that of cisplatin.¹⁷ In vivo activity, for C57BL mice bearing Lewis lung carcinoma, treated with the same compounds exhibited a 73% reduction in tumour growth, which is comparable to cisplatin at or 75%. This research project will explore the feasibility of introducing other bioactive to generate effective dual action anticancer agents using cct-[Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(R₁)(R₂)]²⁺ where R₁ and/or R₂ will be bioactive molecules such as inhibitors.

Key References

1. Stewart, B. W.; Wild, C., World Cancer Report 2014. International Agency for Research on Cancer. World Health Organization 2014, 505.
2. Lu, Q., Molecular reaction mechanism of combination treatments of low-dose cisplatin with radiotherapy and photodynamic therapy. Journal of Medicinal Chemistry 2007, 50, 2601-2604.
3. Ishida, S.; Lee, J.; Thiele, D.; Herskowitz, I., Uptake of the anticancer drug cisplatin mediated by copper transporter Ctr1 in yeast and mammals. Proceedings of the National Academy of Sciences 2002, 99, 14298-14302.
4. Rybak, L.; Whitworth, C.; Mukherjea, D.; Ramkumar, V., Mechanisms of cisplatin-induced ototoxicity and prevention. Hearing Research 2007, 226, 157-167.
5. Petrovic, D.; Stojimirovic, B.; Petrovic, B.; Bugarcic, Z. M.; Bugarcic, Z. D., Studies of interaction between platinum(II) complexes and some biologically relevant molecules. Bioorganic & Medicinal Chemistry 2007, 15, 4203-4211.
6. Alfarouk, K. O.; Stock, C.-M.; Taylor, S.; Walsh, M.; Muddathir, A. K.; Verduzco, D.; Bashir, A. H. H.; Mohammed, O. Y.; Elhassan, G. O.; Harguindey, S.; Reshkin, S. J.; Ibrahim, M. E.; Rauch, C., Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell International 2015, 15, 71.
7. Boulikas, T.; Vougiouka, M., Cisplatin and platinum drugs at the molecular level Oncology Reports 2003, 10, 1663-1682.
8. Perez, R. P., Cellular and Molecular Determinants of Cisplatin Resistance. European Journal of Cancer 1998, 34, 1535-1542.
9. Kartalou, M.; Essignmann, J. M., Mechanism of resistance to cisplatin Mutation Research 2001, 478, 23-43.
10. Johnstone, T. C.; Suntharalingam, K.; Lippard, S. J., The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs. Chemical Reviews 2016, 116 (5), 3436-3486.
11. Krause-Heuer, A. M.; Grünert, R.; Kühne, S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D. D.; Boag, L. R.; Fisher, D. M.; Kasparkova, J.; Malina, J.; Bednarski, P. J.; Brabec, V.; Aldrich-Wright, J. R., Studies of the Mechanism of Action of Platinum(II) Complexes with Potent Cytotoxicity in Human Cancer Cells. Journal of Medicinal Chemistry 2009, 52 (17), 5474-5484.
12. Giandomenico, C. M.; Abrams, M. J.; Murrer, B. A.; Vollano, J. F.; Rheinheimer, M. I.; Wyer, S. B.; Bossard, G. E.; Higgins, J. D., Carboxylation of Kinetically Inert Platinum(IV) Hydroxy Complexes. An Entr.acte.ee into Orally Active Platinum(IV) Antitumor Agents. Inorganic Chemistry 1995, 34 (5), 1015-1021.
13. Hall, M. D.; Hambley, T. W., Platinum(IV) antitumour compounds: their bioinorganic chemistry. Coordination Chemistry Reviews 2002, 232, 49-67.
14. Wexselblatt, E.; Gibson, D., What do we know about the reduction of Pt(IV) pro-drugs? Journal of Inorganic Biochemistry 2012, 117 (Supplement C), 220-229.
15. Yang, J.; Sun, X.; Mao, W.; Sui, M.; Tang, J.; Shen, Y., Conjugate of Pt(IV)-histone deacetylase inhibitor as a prodrug for cancer chemotherapy. Mol Pharm 2012, 9 (10), 2793-800.
16. Raveendran, R.; Braude, J. P.; Wexselblatt, E.; Novohradsky, V.; Stuchlikova, O.; Brabec, V.; Gandin, V.; Gibson, D., Pt(iv) derivatives of cisplatin and oxaliplatin with phenylbutyrate axial ligands are potent cytotoxic agents that act by several mechanisms of action. Chemical Science 2016, 7 (3), 2381-2391.
17. Harper, B. W. J.; Petruzzella, E.; Sirota, R.; Faccioli, F. F.; Aldrich-Wright, J. R.; Gandin, V.; Gibson, D., Synthesis, characterization and in vitro and in vivo anticancer activity of Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)]. Dalton Transactions 2017, 46 (21), 7005-7019.

Primary Supervisor Contact: Prof. William S. Price, w.price@westernsydney.edu.au

Co-Supervisors: Dr Allan Torres

Would suit students interested in: NMR NMR/Physical Chemistry/Physics

Diffusion NMR is routinely used to study various molecular properties, and interactions occurring in solution. This technique is also valuable in MRI as it can be used to probe microscopic structures in biological tissues. Recently, long-lived singlet spin states have been used in NMR diffusion and diffusion-diffraction studies. Unlike regular spin coherences, singlet spin states have significantly longer lifetimes on the order of tens of seconds to a minute making it feasible to study extremely slowly diffusing molecules. In diffusion-diffraction studies, long lived singlet states can potentially be useful for probing structures with larger characteristic distances. In this project, the restricted diffusion of test molecules in glass and flexible silica capillaries will be investigated by utilising singlet spin states and various NMR coherences. The feasibility of performing NMR diffusion experiments in a single capillary with internal diameter of 10-200 micrometres will also be studied.

Primary Supervisor Contact: Prof. William S. Price w.price@westernsydney.edu.au

Co-Supervisors: Dr Tim Stait-Gardner

Would suit students interested in: Biology / Mathematics / Medical Physics / MRI / NMR

Biological tissue is not just an amorphous arrangement of cells. Indeed, most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise tissue microstructure on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure.

Primary Supervisor Contact: Prof. William S. Price, w.price@westernsydney.edu.au

Co-Supervisors: Dr Tim Stait-Gardner

Would suit students interested in: Biology / Chemistry / Mathematics / Medical Physics /MRI / NMR

Modelling self-diffusion in complicated geometries is of fundamental importance in many areas of science including medicine as it will allow more diagnostic information to be extracted from diffusion MRI investigations. Modelling diffusion-controlled reactions - which occur widely in chemical and biochemical systems, and nuclear magnetic resonance diffusion experiments in bounded systems provide many prominent examples of where such modelling is required. Using a simple cellular system as an example, a reacting species diffuses to the enzymatic membrane and then reacts in some way, being either transformed into a product, becoming bound to the surface or transported through the surface. The nature of the interaction at the surface determines the boundary conditions in the modelling. Presently only solutions for some simple geometries are available. This is a serious impediment as most real-world structures that chemical reactions occur in have complicated geometries. Thus, there is a need to develop techniques for modelling diffusive processes near surfaces which are applicable to different geometries and arbitrary boundary conditions.  In this project the student will learn the basics of the underlying theory and develop theoretical and experimental methods for investigating diffusion in restricted systems and their application. It is suitable for mathematically oriented students.

Primary Supervisor Contact: Prof. Janice R. Aldrich-Wright, j.aldrich-wright@westernsydney.edu.au

Co-Supervisors:

Would suit students interested in: Synthetic Chemistry

Platinum anticancer complexes have been a mainstay of cancer chemotherapy for more than three decades and remain in very widespread use for the treatment of solid tumours.¹ Progress has been made in increasing the range of cancers that can be treated by combining platinum complexes with rationally selected molecular targeted agents that decreases the impacts of the toxicity of these complexes. However, the toxicity of the current platinum complexes remains a major impediment to their use at doses that would induce maximum effectiveness and they would achieve the greatest possible benefit from combination with the new molecularly targeted agents. Also, penetration of the platinum complexes into solid tumours, as with nearly all anticancer agents, is sub-optimal which contributes to incomplete destruction of the tumour, leading to relapse and resistance. Therefore, there is a need to develop new complexes that are much less toxic, although are at least as effective in killing cancer cells as the current generation of platinum complexes and can reach all the viable cells in a solid tumour.

In the search to realise Ehrlich’s prediction of a “magic bullet”, we wish to employ a strategy that combines platinum(II) complexes with established anticancer activity targeting molecules to selectively deliver cytotoxic payloads to cancer cells.² An appropriate targeting vector is overexpressed on the surfaces of cancer cells³ or can be directed to specific organelles at the subcellular level to produce cytotoxicity. This strategy can also be used to direct platinum(II) complexes to cancerous tissue by looking for proteins that are expressed on angiogenic blood vessels or by utilising molecules that are activated by the acidic or hypoxic microenvironment with a cancerous mass.⁴

The development of Pt(IV) prodrugs is an increasing attractive field as Pt(IV) complexes have many advantages over Pt(II) in vivo. Platinum(IV) complexes are more kinetically inert than the parent platinum(II) complexes which can be administered orally.^5-6 Once inside cancer cells, platinum(IV) complexes undergo activation by a two-electron reduction that produces a simultaneous release of the parent cytotoxic platinum(II) drug as well as the two axial ligands.⁷ Recently we reported upon several such compounds with valproate (VPA) and phenylbutyrate (PhB) which alter gene transcription that effects arrest, differentiation, apoptosis, and inhibition of tumor angiogenesis.^8,9 The resulting complexes inhibition was demonstrated for cct-[Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(PhB)₂]²⁺ at ~15 times that of cisplatin.¹⁰ In vivo activity, for C57BL mice bearing Lewis lung carcinoma, treated with the same compounds exhibited a 73% reduction in tumour growth, which is comparable to cisplatin at or 75%. This project aims to target cancer cells by utilising unconventional platinum complex, [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane) platinum(II)] dichloride (56MESS). Unlike cisplatin, a clinically used anticancer compound, this complex cannot covalently bind to DNA but it does exhibit up to 100 times more activity than cisplatin in a variety of cell lines with an IC₅₀ of 9.2 ± 2 nM in the L1210 murine leukaemia cell line.¹¹ Increased potency reduces the dosage required, treatment time and the chance of acquired resistance.

The approach here is to explore the feasibility of forming platinum(IV) complexes where the two additional axial ligands can be coordinated to a targeting molecule to produce  effective targeted anticancer agents using cct-[Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(R1)(R₂)]²⁺ where R₁ and R₂ will be targeting molecules) such as: estrogen (overexpressed on the surface of uterine, breast and ovarian cancer cells)¹² and folate receptor proteins (expressed the surface of many cancers, including lung, renal, endometrial, colon, ovarian and breast cancer) to enable preferential uptake by cancer cells via endocytosis.^13-15

Key References

1. Kelland, L. R., The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer 2007, 7, 573-584.
2. Strebhardt, K.; Ullrich, A., Paul Ehrlich’s Magic Bullet Concept: 100 Years of Progress. Nat. Rev. Cancer 2008, 8, 473.
3. Wang, X.; Guo, Z., Targeting and Delivery of Platinum-Based Anticancer Drugs. Chem. Soc. Rev. 2013, 42, 202.
4. Tannock, I. F.; Rotin, D., Acid pH in Tumors and Its Potential for Therapeutic Exploitation. Cancer Res. 1989, 49, 4373.
5. Giandomenico, C. M.; Abrams, M. J.; Murrer, B. A.; Vollano, J. F.; Rheinheimer, M. I.; Wyer, S. B.; Bossard, G. E.; Higgins, J. D., Carboxylation of Kinetically Inert Platinum(IV) Hydroxy Complexes. An Entr.acte.ee into Orally Active Platinum(IV) Antitumor Agents. Inorganic Chemistry 1995, 34 (5), 1015-1021.
6. Hall, M. D.; Hambley, T. W., Platinum(IV) antitumour compounds: their bioinorganic chemistry. Coordination Chemistry Reviews 2002, 232, 49-67.
7. Wexselblatt, E.; Gibson, D., What do we know about the reduction of Pt(IV) pro-drugs? Journal of Inorganic Biochemistry 2012, 117 (Supplement C), 220-229.
8. Yang, J.; Sun, X.; Mao, W.; Sui, M.; Tang, J.; Shen, Y., Conjugate of Pt(IV)-histone deacetylase inhibitor as a prodrug for cancer chemotherapy. Mol Pharm 2012, 9 (10), 2793-800.
9. Raveendran, R.; Braude, J. P.; Wexselblatt, E.; Novohradsky, V.; Stuchlikova, O.; Brabec, V.; Gandin, V.; Gibson, D., Pt(iv) derivatives of cisplatin and oxaliplatin with phenylbutyrate axial ligands are potent cytotoxic agents that act by several mechanisms of action. Chemical Science 2016, 7 (3), 2381-2391.
10. Harper, B. W. J.; Petruzzella, E.; Sirota, R.; Faccioli, F. F.; Aldrich-Wright, J. R.; Gandin, V.; Gibson, D., Synthesis, characterization and in vitro and in vivo anticancer activity of Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)]. Dalton Transactions 2017, 46 (21), 7005-7019.
11. Krause-Heuer, A. M.; Grünert, R.; Kühne, S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D. D.; Boag, L. R.; Fisher, D. M.; Kasparkova, J.; Malina, J.; Bednarski, P. J.; Brabec, V.; Aldrich-Wright, J. R., Studies of the Mechanism of Action of Platinum(II) Complexes with Potent Cytotoxicity in Human Cancer Cells. J. Med. Chem. 2009, 52 (17), 5474-5484.
12. Gagnon, V.; St-Germain, M.-E.; Descôteaux, C.; Provencher-Mandeville, J.; Parent, S.; Mandal, S. K.; Asselin, E.; Bérubé, G., Biological evaluation of novel estrogen-platinum(II) hybrid molecules on uterine and ovarian cancers-molecular modeling studies. Bioorganic and Medicinal Chemistry Letters 2004, 14, 5919-5924.
13. Krause-Heuer, A.; Grant, M. P.; Orkey, N.; Aldrich-Wright, J. R., Drug delivery devices and targeting agents for platinum(II) anticancer complexes. Australian Journal of Chemistry 2008, 61, 675-681.
14. Bae, Y.; Jang, W. D.; Nishiyama, N.; Fukushima, S.; Kataoka, K., Multifunctional polymeric micelles with folate-mediated cancer cell targeting and pH-triggered drug releasing properties for active intracellular drug delivery. Mol. BioSyst 2005, 1, 242-250.
15. Mueller, C.; Schubiger, P. A.; Schibli, R., In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer. Eur. J. Nucl. Med. Mol. Imaging 2006, 33, 1162-1170.

Primary Supervisor Contact: Prof. William S. Price w.price@westernsydney.edu.au

Co-Supervisors: Dr Tim Stait-Gardner

Would suit students interested in: Mathematics / MRI / NMR / Physics

Understanding spin-dynamics is of fundamental importance for NMR students. However, in many instances to understand such complicated theory we must resort to computer simulation, which turns boring memorization into exciting practice. Numerical and symbolic algebra simulation programs can be used for the development of new NMR pulse sequences. In this project students will perform NMR simulations based on a full understanding of spin-dynamics to enhance the development of new NMR methods (e.g., water suppression and diffusion measurements). Exact numerical simulations of NMR experiments are often required for the development of new techniques and for the extraction of structural and dynamic information from the spectra. Designing and synthesising molecules that selectively bind to Quadraplex DNA

Primary Supervisor Contact: Dr Gang Zheng g.zheng@westernsydney.edu.au

Co-Supervisors: Dr Tim Stait-Gardner, Dr Nirbhay Yadav (Johns Hopkins), Prof. William S Price

Would suit students interested in: Chemistry / Medical Physicss / NMR / MRI

In general chemistry, we’ve learned that acidic protons are constantly hopping between solute molecules and water molecules. The efficiency of this hopping process is affected by many factors and one of these factors, pH, is directly linked to the disease state of biological tissues (e.g., metastasis of cancer), which means we can achieve medical diagnosis by measuring the micro-environmental acidity in diseased tissues. In this project, the student will study the basics of chemical kinetics, nuclear magnetic resonance (NMR), and experimental magnetic resonance imaging (MRI). From this background, the student will then develop novel chemical exchange saturation transfer (CEST) techniques for the study of proton exchange in solutions and tissues, focusing on the observation and quantification of the CEST peaks close to the water signal of diagnostically important metabolites such as myo-inositol and glucose in the NMR spectrum. If the newly developed techniques afford the distinction between metabolite and water signals in the water-proximate region in the experiments on phantom samples, they will be applied in animal experiments in the School of Medicine, Johns Hopkins University.

Key References:

• Li, Y., H. Chen, J. Xu, N.N. Yadav, K.W.Y. Chan, L. Luo, M.T. McMahon, B. Vogelstein, P.C.M. van Zijl, S. Zhou, and G. Liu. CEST theranostics: label-free MR imaging of anticancer drugs. Oncotarget, 2016. 7:6369-6378.
• Yang, X., N.N. Yadav, X. Song, S. Ray Banerjee, H. Edelman, I. Minn, P.C.M. van Zijl, M.G. Pomper, and M.T. McMahon. Tuning Phenols with Intra-Molecular Bond Shifted HYdrogens (IM-SHY) as diaCEST MRI Contrast Agents.Chemistry – A European Journal, 2014. 20:15824-15832.

Primary Supervisor Contact: Prof. William S. Price, w.price@westernsydney.edu.au

Co-Supervisors: Dr Scott A. Willis, Dr Allan Torres

Would suit students interested in: Biology / Chemistry / NMR

Freeze tolerance is important for life that exists in low temperature environments. Protection strategies include the use of antifreeze proteins to prevent ice crystal growth or the use of ice nucleation proteins (INPs). INPs initiate ice formation earlier so that the organism has a chance to respond to the freezing for thermal protection or could be used as a means of retrieving nutrients from plants. INPs are thought to bind to water molecules in a way that resembles an ice crystal such that further nucleation is promoted but the mechanism is not fully understood. As such a study of translational diffusion and hydration of these proteins in aqueous solutions at various temperatures is pertinent for understanding this and would be of interest for potential applications of these proteins.