Chemical Sciences

Applications for 2023-2024 are now closed.

Peptide-Dye conjugates as tumour targeting drug delivery

Supervisors

A/Prof Paul Harris

Dr Peter Choi

Dr Jiney Jose

Discipline

School of Biological Sciences

School of Chemical Sciences

Auckland Cancer Society Research Centre

Project code: SCI019

Project

Methods to specifically target cytotoxic drugs to tumour cells are a successful way to treat cancers exemplified by the antibody drug conjugates, such as Kadcyla. However, as a biological agent, there are difficulties with its production, potency and side effects. Using small molecules dyes that are selective only for cancer cells are an alternative way to target drugs directly and as a non-biological are easier to synthesise, handle and can be conjugated to virtually any anti-cancer drug with an appropriate chemical linker. This project will involve chemical synthesis of both the dye and peptide and explore methods to conjugate both moieties into suitable construct.

Ideal student

A background in synthetic chemistry is mandatory and an interest in biological assays would be beneficial.

See: Jose et al Bioconjugate Chem. 2020, 31, 7, 1724–1739

Novel peptide-based antibiotics

Supervisors

A/Prof Paul Harris
A/Prof Viji Sarojini
Prof Alan Davidson
Dr Veronika Sander

Discipline

School of Biological Sciences

School of Chemical Sciences

Faculty of Medical and Health Sciences

Project code: SCI020

Project

Antibiotic resistance has been recognised by the WHO as one of the greatest threats to humanity and infectious diseases rank as the second most common cause of death worldwide. New antibiotics are desperately needed and if nothing is done by 2050 it is estimated > 10M people will die per annum, which is more that cancer and diabetes.

Cyclic lipopeptides are an emerging subset of peptide-based antibiotics (e.g., FDA-approved daptomycin and polymyxin) containing a lipid or fatty acid. They have been shown to possess clinical efficacy and are used as the “last line of defence” against otherwise untreatable bacterial infections. Despite their promise, undesired toxicity is a significant drawback.

We are developing novel, non-toxic derivatives of naturally occurring lipopeptide antibiotics (e.g., Fig. 1) by modifying the chemistry of the lipid tail. Novel antibiotic analogues will undergo biological testing against multi-drug resistant (MRD) strains of bacteria and evaluation of potential toxicity.

Skills developed

Successful candidates will use organic synthesis and modern methods of solid phase peptide synthesis. Candidates will also have the opportunity to undertake and learn biological assays if they desire.

References

See: Harris et al. ACS Infect. Dis. 2022, 8, 2413
See: Sarojini et al. J. Med. Chem. 2015, 58, 2, 625

Total chemical synthesis of naturally occurring anti-cancer peptaibols

Supervisors

A/Prof. Paul Harris

A/Prof Dan Furkert

Discipline

School of Biological Sciences

School of Chemical Sciences

Project code: SCI021

Project

One emerging field of natural products being evaluated for anti-cancer activity are the naturally occurring peptaibols (8-20 amino acid residues) which display a variety of biological functions due to the occurrence of voltage-dependant ion channels in lipid bilayer cell membranes that these peptaibols influence, leading to their inherent cytotoxicity.
In 2015, Lin et. al. reported the isolation of peptaibols Microbacterin A and B extracted from the deep sea actinomycete Microbacterium sediminis sp. nov. YLB-01. These novel compounds exhibited antitumour activity against a variety of human cancer cell lines ranging from A2780 (human ovarian cancer cell), A549 (human lung cancer cell), Bel-7402 (human hepatoma cell), BGC-823 (human gastric cancer cell) and HCT-8 (human intestinal adenocarcinoma cell) with IC50 values ranging from 1.03-5.93 µM.

In this project we will prepare the unique amino acid (R,S)-3-amino-2-hydroxy-3-methylbutanoic acid (AHV) as a racemate and employ advanced methods to separate and characterise the two enantiomers. The correct (R) enantiomer will be equipped with suitable protecting groups for solid phase peptide synthesis and the first total chemical synthesis will be performed to afford the natural product. Comparison of the spectroscopic data of the synthetic Microbacterin with that published will confirm the structure and allow subsequent structure activity studies to identify more potent leads.

Requirement

An interest in organic synthesis and modern methods of solid phase peptide synthesis will be required.

References

See: Org. Lett. 2015, 17 (5), 1220–1223

Peptide therapeutics for treatment of diabetes

Supervisors

A/Prof. Paul Harris

Prof Kerry Loomes

Discipline

School of Biological Sciences

School of Chemical Sciences

Project code: SCI022

Project

There is still an unmet need to effectively treat metabolic disease. This research addresses a new strategy to combat obesity and its associated metabolic diseases such as type-2 diabetes mellitus and cardiovascular disease. This therapeutic approach focuses on enhancing mitochondrial capacity to counteract insulin resistance and enhance muscle mass.

Strong evidence suggests that decreased mitochondrial function contributes to fatty acid dysregulation that contributes to insulin resistance. We will develop peptide antagonists from a 56 amino acid venom peptide, HCRG21, derived from the sea anemone H. crispa (left) HCRG21 is a known peptide neurotoxin that can act at a specific receptor to exert its beneficial metabolic effects. It contains three disulphide bonds that create a 3-D architecture, and this project will undertake a chemical synthesis of HCRG21 that precisely installs the correct disulphide configuration using peptide chemistry, protein folding and bioconjugation.

An interest in peptide and protein chemistry is needed but assumes no prior experimental techniques in this area.

See: Marine Drugs. 2016; 14(12):229

Total chemical synthesis of the macrocyclic anti-cancer drug Telomestatin

Supervisors

A/Prof. Paul Harris

Prof Jon Sperry

Discipline

School of Biological Sciences

School of Chemical Sciences

Project code: SCI023

Project

Telomerase is an enzyme involved in DNA replication and has been implicated in malignant cancers. Telomestatin (above) is a cyclic peptide-based inhibitor of telomerase with nanomolar potency in vitro but translation to the clinic has been hampered by limited availability of material as chemical synthesis has proven to be difficult. Detailed structure activity relationships are therefore unable to be undertaken. Telomestatin is essentially a cyclic peptide consisting of threonine, serine and cysteine amino acids that have been dehydrated to form the corresponding oxazoles (serine/threonine) and thiazoles (cysteine). This project will embark on a new total synthesis of Telomestatin from an all-amino acid cyclic precursor, prepared via solid phase peptide synthesis followed by examination of chemical dehydration conditions to form the oxazoles and thiozoles in a one-pot manner.

Requirements

Students will need to have a solid background in synthetic organic chemistry and an interest in assembly of cyclic peptides by solid phase peptide synthesis.

References

See: J. Am. Chem. Soc. 2011, 133, 4, 1044–1051

Biomimetic synthesis of marine pyridoacridine alkaloids

Supervisor

Prof Brent Copp

Discipline

School of Chemical Sciences

Project code: SCI024

Project

The goal of biomimetic synthesis of natural products is to access complex molecules that are difficult to obtain through traditional chemical synthesis or extraction from natural sources. By using biomimetic principles, we hope to develop more efficient, economical, and sustainable synthetic routes to produce natural products with potential applications in medicine. We have recently developed a biomimetic synthesis of styelsamine A from simple precursors. In this project we will explore methods to transform styelsamine A into examples of arnoamine alkaloids, cytotoxic natural products isolated from tropical sea squirts.

Ideal student

The student undertaking this project will be involved in organic synthesis, purification and compound characterisation (NMR, MS, etc). They should have a reasonable knowledge of synthetic chemistry.

Biomimetic synthetic approach to the New Zealand marine natural products, the kottamides

Supervisor

Prof Brent Copp

Discipline

School of Chemical Sciences

Project code: SCI025

Project

Marine natural products are small organic molecules biosynthesised by organisms that play ecological roles to increase the fitness and survival of the producing organism. The natural products can provide inspiration for the development of new medicines or prompt the development of new methodologies for their synthesis. We use biomimetic principles to target the synthesis of natural products – in doing so we hope to develop more efficient, economical, and sustainable synthetic routes to produce natural products with potential applications in medicine.

We isolated a family of imidazolone-containing natural products, the kottamides, from an ascidian that was collected at the remote Three Kings Islands, north of New Zealand. We propose that the kottamides are biosynthesised by the ascidian from a tripeptide precursor, that undergoes ring closure mediated by the presence of electrophilic dehydro-amino acids. As no syntheses have been reported for this class of natural product, we are interested in applying biomimetic synthesis principles to make either the natural products themselves or natural product-like molecules and evaluate them for a range of biological properties.

Ideal student

The student undertaking this project will be involved in organic synthesis, purification and compound characterisation (NMR, MS, etc). They should have a reasonable knowledge of synthetic chemistry.

Biomimetic synthetic approach to sulfur-containing biologically active marine natural products

Supervisor

Prof Brent Copp

Discipline

School of Chemical Sciences

Project code: SCI026

Project

Pyridoacridine alkaloids are a class of marine natural products that have complicated structures and are difficult to synthesise. We are using biomimetic principles to develop efficient, economical, and sustainable synthetic routes to prepare pyridoacridines with potential applications in medicine. Shermilamine B is an example of a more complicated pyridoacridine alkaloid that is unusual in that it contains a sulfur substituted thiazinone ring. We plan to use methods we have developed to prepare pyridoacridines using simple precursor compounds. In the case of shermilamine B, we are going to start the reaction sequence from thiol substituted dopamine quinone analogues, which are actually natural products themselves, involved in the formation of red pigmented hair and feathers.

Ideal student

The student undertaking this project will be involved in organic synthesis, purification and compound characterisation (NMR, MS, etc). They should have a reasonable knowledge of synthetic chemistry.

Bioorganometallic Anticancer Chemotherapeutics: Preparation of Metal Complexes with Bioactive Ligands

Supervisor

Prof. Christian Hartinger

Discipline

School of Chemical Sciences

Project code: SCI027

Project

The coordination of bioactive ligand systems to metal centres results in multimodal anticancer agents, i.e., anticancer drugs that have more than one of mode action. This design strategy is a promising route to overcome major limitations of current cancer chemotherapeutics. We will develop in this project new complexes between organometallic moieties and bioactive ligand systems and study their anticancer activity.

Design of Multimodal Organometallic Anticancer Agents

Supervisor

Prof. Christian Hartinger

Discipline

School of Chemical Sciences

Project code: SCI028

Project

In the past decade the design of targeted anticancer agents was among the most prolific research areas. However, more recently it has become apparent that the combination of more than one pharmacophore in a single molecule can result in anticancer agents with advantageous properties. In this project, we will work on the preparation of a new compound class to be tested on its tumour-inhibiting properties.

Design and Applications of Organometallic Complexes for Catalysis

Supervisors

Prof. Christian Hartinger

Prof. James Wright

Discipline

School of Chemical Sciences

Project code: SCI029

Project

The production of everyday products, such as pharmaceuticals, fertilisers and functional materials, is reliant on efficient chemical transformations to yield high amounts of the desired products at low cost. In this project, we will use different ruthenium complexes and study their catalytic activity in important chemical transformations with relevance to industry.

Design and Applications of Organometallic Complexes for Catalysis

Supervisor

Prof. Christian Hartinger

Discipline

School of Chemical Sciences

Project code: SCI030

Project

Understanding the mode of action of anticancer agents at the molecular level is key to develop the next generation anticancer drugs. In this project, we will investigate the biomolecule interaction of metallodrugs using advanced bioanalytical methods to characterize reaction products and/or binding kinetics. These studies are important to select compounds for further preclinical development.

Supramolecular structures and their use for targeted delivery of anticancer agents

Supervisor

Prof. Christian Hartinger

Discipline

School of Chemical Sciences

Project code: SCI031

Project

Stimulus responsive supramolecular structure may provide a means to deliver anticancer agents selectively to the tumour, and the stimulus can be used to release an anticancer drug from the structure. In this project, we will prepare ditopic ligands that will be coordinated to metal centres to form such supramolecular structures. The supramolecules will be characterised and their ability to host and release anticancer drugs will be assessed.

Controlling reaction outcomes with nanostructured ionic liquids

Supervisor

Dr Cameron Weber

Discipline

School of Chemical Sciences

Project code: SCI032

Project

Ionic liquids, low melting salts, can form sponge-like nanostructures comprised of alternating polar and non-polar domains. These domains provide the opportunity to control the outcome of reactions by affecting the frequency of collisions between reactants. We have recently demonstrated that the selection of ionic liquid ions in nanostructured ionic liquids can have a critical role in influencing how these solvents affect chemical reactions.

This project will explore the effect of ionic liquid nanostructure on the kinetics of fundamentally important organic reactions towards the goal of being able to design solvents that can control reaction outcomes (rate and selectivity) and minimise the production of chemical waste.

How accurate are polarity measures of deep eutectic solvents?

Supervisor

Dr Cameron Weber

Discipline

School of Chemical Sciences

Project code: SCI033

Project

Deep eutectic solvents (DESs) are mixtures that have melting points below the constituents of the mixture, forming room temperature liquids from solid components. The polarity of DESs is typically characterised using methods that have been validated for ionic liquids and conventional organic solvents. Our preliminary results indicate that these measures tend to overstate the polarity of DESs when compared to their performance as solvents.

This project will screen the performance of DESs against conventional solvents and ionic liquids for benchmark processes such as the solubility of important solutes or model chemical reactions and explore the relationship between measures of solvent polarity and performance. These outcomes will be used to inform future measures of solvent polarity for DESs and enable better informed solvent selection for processes that DESs can be useful for.

Bio-based thermal insulation materials

Supervisors

Dr Cameron Weber

Dr Kaveh Shahbaz (Chemical and Materials Engineering)

Discipline

School of Chemical Sciences

Project code: SCI034

Project

Phase change materials (PCMs) store thermal energy through the latent heat of a phase change (e.g. a solid melting to form a liquid). To prevent leakage PCMs are often encapsulated within polymer microbeads which is an expensive process that generates significant plastic waste.

This project will explore the development of novel composite materials that use a modified support material made from forestry waste products and incorporate agricultural waste products as the PCMs. The effect of the modification of the support on the properties of the PCM and the viability of the composite as a thermal storage material will be explored.

Targeting novel chitin depolymerisation products

Supervisor

Dr Cameron Weber

Assoc. Prof. Jonathan Sperry

Discipline

School of Chemical Sciences

Project code: SCI035

Project

Chitin, found in crustacean shells and insect exoskeletons, is the second most abundant biopolymer on Earth and the most abundant biopolymer containing nitrogen. Chitin represents a potential input for future biorefineries as a pathway to prepare amines without relying on the energy-intensive Haber-Bosch process.

This project will explore the use of alternative solvents for the solubilisation and depolymerisation of chitin to target the preparation of novel anilines that could prove useful as intermediates for fine chemical products.

Dynamic Microfluidics using High-Speed Photography

Supervisor

Geoff Willmott

Discipline

School of Chemical Sciences

Project code: SCI036

Project

The Dynamic Microfluidics Laboratory uses high-speed photography to study the motion of fluids at small length scales. Various projects are available to study phenomena including (for example):

  • Impacts of drops on to surfaces, especially fluids of industrial interest which are often non-Newtonian (e.g. milk).
  • The fate of droplets floating in air, relevant (for example) to the spread of viruses.
  • The detailed dynamics of capillary uptake.

Ideal student / skills gained

The student should be an aspiring physical/materials or food scientist, who will gain skills and experience relating to materials characterization, high-speed photography and/or image analysis.

Janus Spheres

Supervisor

Geoff Willmott

Discipline

School of Chemical Sciences

Project code: SCI037

Project

This project will study Janus spheres, which are microspheres which have two (or more) different surface coatings applied to them. We are interested in how the asymmetry of these spheres affects the formation of self-assembling particle clusters. Janus particle clusters could be used to develop reconfigurable components for sustainable technologies, and they also serve as a good model for biological self-assembly.

To study clustering, particles in solution are observed as they come together on a microfluidic chip.

Ideal student / skills gained

The student should be an aspiring physical/materials chemist, who will gain skills and experience relating to materials characterization, microfluidics, fabrication, and/or image analysis methods.

Lab website
https://fluidics.physics.auckland.ac.nz/

Liposome Mechanics

Supervisor

Geoff Willmott

Discipline

School of Chemical Sciences

Project code: SCI038

Project

We have developed a method (known as ‘aspiration’) which can measure the mechanical properties of soft microparticles using the humble pipette. The important role of such mechanical properties in (bio-)medical research is emerging. This project will apply aspiration to the measurement of liposomes, an interesting family of synthetic micro- and nanoparticles analogous to cells, and with potential drug delivery applications.

Ideal student / skills gained

The student should be an aspiring physical/materials scientist, who will gain skills and experience relating to materials fabrication and characterization.

Lab website
https://fluidics.physics.auckland.ac.nz/

Natural Product Cytotoxic Payloads for Antibody–Drug Conjugates

Supervisors

Dr Iman Kavianinia

Distinguished Professor Margaret Brimble

Discipline

School of Chemical Sciences

Project code: SCI039

Project

Antibody-drug conjugates (ADCs) are a clinically proven class of medicines used in the treatment of various cancers. Utilisation of the exquisite selectivity of antibody targeting to cancer epitopes coupled to delivery of highly potent small molecules is revolutionising modern oncology. Given the modular nature of the ADC design concept, the future potential of this field is truly vast, and will rely on the discovery of:

i) new antibody-antigen couples

ii) novel linker chemistries

iii) the discovery of highly potent cytotoxins for conjugation

Critically, the availability of suitably potent, stable cytotoxic agents is considered rate-limiting for progress in this field. Cytotoxic peptide natural products provide a rich source of anticancer agents that can be readily appended to antibodies using amino acid-based conjugation technology.

Skills gained

This research project provides a unique opportunity to develop a novel class of cytotoxin with optimal properties for use in ADCs. The student undertaking this project will be involved in modern solid-phase peptide synthesis, HPLC purification and compound characterisation using related spectroscopic techniques.

Linker Design for Antibody-Drug Conjugates

Supervisors

Dr Iman Kavianinia

Distinguished Professor Margaret Brimble

Discipline

School of Chemical Sciences

Project code: SCI040

Figure 1. General antibody-drug conjugates structure

Project

Antibody-drug conjugates (ADCs) are a clinically proven class of medicines used in the treatment of various cancers. The ADCs utilise monoclonal antibodies (mAbs) to specifically bind to the corresponding antigens present on the surface of cancer cells. This selective binding minimises the systemic toxicity associated with the anti-cancer treatment and significantly increases the pharmacological activity of the conjugated cytotoxin. The three main components of ADCs are the desirable monoclonal antibody, an appropriate linker and an active cytotoxic drug, Figure 1.

Linkers designed to be cleaved under specific cellular conditions include acid-labile hydrazone linkers sensitive to the low-pH conditions in the endosome and lysosome, disulfide-based linkers that can be reduced by the high (millimolar) levels of reduced glutathione in the cell cytosol compared to serum, or dipeptide linkers cleaved by specific lysosomal proteases. Despite considerable effort undertaken to design a stable linker between the antibody and cytotoxic agent, systemic toxicity is observed in several ADCs in clinical development. Therefore, interest in designing a suitable chemical linker that helps the antibody to deliver the cytotoxic agent specifically to cancer cell has become an important target for scientists involved in the development of novel antibody-drug conjugates.

The proposed research aims to generate a new class cleavable linkers that can facilitate efficient release of the cytotoxic agent at a targeted tumor site.

Synthetic biology for the sustainable production of natural medicines from corals

Supervisor

Tristan de Rond

Discipline

School of Chemical Sciences

Project code: SCI041

Project

Terpenoids are molecules naturally produced by many organisms such as plants, fungi and bacteria, providing functions such as defence, communication, and attracting pollinators. Plant terpenoids – perhaps most famous as the distinctive fragrances of citrus, eucalyptus, mint, and many other plants – have also been harnessed as life-saving medicines, such as the anticancer drug Taxol from the Pacific yew (Taxus brevifolia) and the antimalarial agent artemisinin from sweet wormwood (Artemisia annua).

In the marine environment, soft corals and sponges produce a broad repertoire of terpenoids. Like plant terpenoids, these terpenoids show promising medicinal activities. However, acquiring enough terpenoid for further medicinal testing and, eventually, supplying sufficient amounts for therapeutic uses, has historically required harvesting corals in quantities that are environmentally unsustainable.

One way to sustainably produce terpenoids is by means of synthetic biology. For instance, artemisinin harvested from Artemisia annua used to suffer from dramatic supply and demand fluctuations. By identifying the genes encoding the enzymes responsible for artemisinin biosynthesis in Artemesia annua and expressing them in baker’s yeast, artemisinin can now be reliably and sustainably produced through fermentation (https://doi.org/10.1038/nature04640).

For a long time, it was deemed impossible to apply this strategy to coral and sponge terpenoids because the enzymes responsible for terpenoid production in corals were unknown. However, this has changed due to a recent discovery, where we identified the enzymes that catalyse the first step of terpenoid biosynthesis in corals (https://doi.org/10.1038/s41589-022-01026-2) and in sponges (https://doi.org/10.1073/pnas.2220934120).

In this project, we will apply our newfound knowledge of marine terpenoid biosynthesis to establish microbial cell factories for the sustainable production of marine terpenes.

Shedding light on metabolic dark matter through genome mining

Supervisor

Tristan de Rond

Discipline

School of Chemical Sciences

Project code: SCI042

Project

Our knowledge of nature’s diversity of enzymatic transformations is crucial to advancing research in a multitude of disciplines. For instance, our ability to predict metabolic capacity from genome sequences enables new insights in human health and ecology, while the development of bioprocesses to produce chemicals in an environmentally benign fashion relies on the availability of a well-stocked biocatalytic toolbox. Billions of years of evolution have resulted in immense natural genetic diversity, which we are rapidly starting to uncover using modern sequencing technologies. However, the functional assignment of the enzymes encoded by this sequence diversity is lagging. Genome mining seeks to explore this “metabolic dark matter” for new biocatalysts, pharmaceuticals and biochemical insight (https://doi.org/10.1038/s41576-021-00363-7).

Our lab has recently developed new algorithms to identify unique un-annotated genes coding for enzymes in genomic data, which led us to discover the first known oxazolone synthetase enzyme (https://doi.org/10.1038/s41589-021-00808-4).

In this project, the student will apply genome mining to a selection of other un-annotated genes, in the hopes of shedding light on even more of this metabolic dark matter. Biosynthetic genes will be expressed heterologously, and the presence of metabolic products will be determined using modern analytical chemistry methods. Novel molecules will be purified, their structures determined, and they will be tested for medicinal potential.

Students will be able to learn valuable laboratory skills in microbiology, molecular cloning, organic chemistry and analytical chemistry, as well as hone their skills reading the literature and presenting their results.

Requirement

Some knowledge of molecular biology and organic chemistry.

Timing

Background and computational research may be performed remotely in December, but the student will need to be physically present for laboratory work in starting in early January.

Using Modern Technology for Greener Chemical Synthesis

Supervisor

Dr Zoe Wilson

Discipline

School of Chemical Sciences

Project code: SCI043

Project

Making molecules in a safe and sustainable manner is a vital focus for modern chemists. To achieve this, we must embrace advances in technology, such as the use of flow chemistry. Flow chemistry involves pumping liquid streams through small diameter tubes to effect reactions continuously, either by joining two streams of reagents together, or by flowing the reaction stream through a range of reactors. When compared to traditional chemical synthesis, flow chemistry offers many benefits (see figure). This project would focus on harnessing these benefits to improve chemical reactions in terms of sustainability/greenness.

Skills gained and ideal student

This project would allow students to get hands-on chemical synthesis experience, both using traditional “batch” chemistry but also in the up-and-coming area of flow chemistry, while applying green chemistry principles, and would suit students with an interest in green chemistry and/or synthetic organic chemistry.

SAR Study to Combat Antimicrobial Resistance

Supervisors

Dr Alan Cameron

Distinguished Professor Dame Margaret Brimble

Discipline

School of Chemical Sciences

Project code: SCI044

(Upper) Chemical structure of Macolacin with modification sites highlighted; (lower) activity of macolacin towards polymyxin resistant isolates.

Project

Antibiotic resistance is recognised by the WHO as one of the greatest threats to humanity, and infectious diseases rank as the second most common cause of death worldwide. Polymyxin antibiotics are the current last-line of defence for drug-resistant Gram-negative infections, but are severely nephrotoxic. Most worryingly, since 2015, a mobile resistance gene (mcr-1) has been spreading globally and making our last resort antibiotic ineffective.

In 2022, macolacin was discovered. Macolacin is a new polymyxin scaffold that retains potent activity towards mcr-1 mediated polymyxin-resistant Gram-negative bacteria.

This project will include a Structure-Activity-Relationship (SAR) study of macolacin, aiming to prepare new analogues with diminished toxicity that could replace polymyxins as last-line of defence antibiotics in the clinic.

Skills gained

Successful candidates will use organic synthesis techniques and modern methods of solid phase peptide synthesis. Candidates will also have the opportunity to undertake and learn biological assays if they desire.

Virus Activated Cancer Prodrugs

Supervisors

Dr Alan Cameron

Distinguished Professor Dame Margaret Brimble

Discipline

School of Chemical Sciences

Project code: SCI045

Project

Oncolytic viruses are an emerging class of therapeutics for cancer treatment. These viruses selectively infect and lyse cancerous cells. However, these therapies still suffer from certain limitations, perhaps the greatest of which is immune clearance of the virus prior to complete tumour destruction. To elicit maximal efficacy, these viruses could be used in combination with chemotherapeutics or radiotherapy.
The presence of viral infection provides new opportunities to develop selectively targeted chemotherapeutics.

This project seeks to develop a novel Virus-Directed Enzyme Prodrug Therapy (VDEPT). Cytotoxic payloads will be developed and conjugated to an inactivating peptide sequence that is selectively cleaved by the protease of a promising oncolytic virus to release the active cytotoxin selectively in the tumour microenvironment. Thus, the project seeks to develop a novel prodrug and combination therapy. A key aspect of the research will be optimising the self-immolating cleavable linker system for a favourable rate of payload release.

3-component prodrug activation by viral protease in the tumour microenvironment.

The project is an active collaboration with the University of Otago.

Skills gained

The successful candidate will develop skills in modern organic chemical synthesis, Solid Phase Peptide Synthesis (SPPS), reverse phase-HPLC and may also have the opportunity to conduct biological assays/enzyme assays.

Electrochemical Organic Synthesis

Supervisor

Professor Jonathan Sperry

Discipline

School of Chemical Sciences

Project code: SCI046

Project

The overarching aim of this project is to demonstrate that electrochemical synthesis is an enabling green chemistry technique that has an enormous role to play in the evolution of sustainable chemical production. We will achieve this goal by developing several electrochemical dehydrogenative couplings (and related reactions) that can be used to assemble heterocyclic scaffolds of value to a variety of allied fields including chemical biology, materials science and medicine.

As this methodology does not require chemical reagents, employs unfunctionalised substrates and the only theoretical by-product is hydrogen, the environmental and economic implications of these synthetic procedures is minimal. Precise control of the oxidation potential is straightforward. Moreover, as the oxidation occurs adjacent to the anode and not in a bulk solution phase, as occurs with chemical oxidants, side reactions are minimised.

Requirements

Interest in green chemistry, complex organic synthesis, electrochemistry.

Chemical Synthesis using Biomass-Derived Building Blocks

Supervisor

Professor Jonathan Sperry

Discipline

School of Chemical Sciences

Project code: SCI047

Project

The global chemical industry is committed to reducing the carbon footprint embedded within its supply chains. Employ molecules derived from biorenewable sources in the production of will valuable chemicals will help achieve this goal. This project will investigate the synthesis of fine chemicals from heteroatom-rich bio-based platforms, such as cellulose, chitin or phytic acid.

Requirements

An interest in Green Chemistry and complex organic synthesis

Mechanochemical synthesis

Supervisor

Professor Jonathan Sperry

Discipline

School of Chemical Sciences

Project code: SCI048

Project

Solvent waste from the chemical industry is an enormous financial and environmental burden. One potential solution to this issue is to synthesise valuable compounds in the solid state using mechanochemistry, an underexplored technique in chemical synthesis. In this project, the mechanochemical synthesis of medicinally important heterocycles and pharmaceutical motifs will be developed, with the aim to eliminate solvent from these processes.

Requirement

Interest in Green Chemistry and complex organic synthesis

Natural Product Inspired Therapeutics for Psychiatric Disease

Supervisor

Professor Jonathan Sperry

Discipline

School of Chemical Sciences

Project code: SCI049

Project

Natural products (secondary metabolites) contain a level of structural and chemical diversity that is unsurpassed by man-made libraries. Natural products are produced by organisms after millions of years of evolution, having undergone several rounds of ‘natural optimisation’ to interact efficiently with biological macromolecules. Indole natural products have a unique ability to permeate the blood brain barrier (BBB) and have a rich history of therapeutic use in Central Nervous System disease.

With collaborators in the US, this project will examine the synthesis of indole alkaloids that are unattainable from the natural source, and their subsequent biological evaluation against mammalian brain receptors implicated in mood.

Requirement

Interest in medicinal chemistry

Mechanochemical Destruction of Forever Chemicals

Supervisor

Professor Jonathan Sperry

Discipline

School of Chemical Sciences

Project code: SCI050

Project

The burden of resolving the environmental issues associated with widespread industrial and commercial use of per- and polyfluoroalkyl substances (PFASs) is enormous. PFASs are extremely persistent upon release to the environment and are associated with negative health effects. The high stability of these industrial chemicals makes destruction challenging and technologies capable of scaling to a level required to treat PFAS-impacted soil and legacy stockpiles such as aqueous film-forming foams (AFFFs) are urgently required.

This project will integrate students into an ongoing ‘forever chemical’ destruction programme, in collaboration with a NZ-based company (Environmental Decontamination Limited) and the United States Environmental Protection Agency.

Requirement

Interest in Environmental Chemistry/Green Chemistry.

Designing variants of polyphenol-oxidase to slow down the spoilage of food and beverages.

Supervisor

Davide Mercadante

Discipline

School of Chemical Sciences

Project code: SCI051

Project

Polyphenol oxidases (PPO) are plant enzymes involved in the browning of food commodities. By catalysing the conversion of polyphenols to quinones PPOs generate the precursor of polymeric melamins, determining the browning of food products and triggering spoilage.

The availability of quinones to be converted into melamines is regulated by the activity of PPO, which is linked to the accessibility of substrates for the PPO’s active site. More importantly, and relevant to this project, recent studies have suggested that this accessibility is regulated by the dynamics of specific residues within the PPO active site.

In this project, you will undertake molecular simulations to understand the dynamics of different PPO enzymes, with particular focus on their active site.

Once you understand the dynamic behaviour of the enzyme, you will rationally design PPO mutants that can have limited accessibility for substrates to their active site. You will thus carry out molecular simulations and have the opportunity to apply mutations useful to create new food commodities with lower browning propensities.

For this project you won’t need any prior experience with molecular simulations or particular computer skills.

Ideal candidate

Prior knowledge of protein chemistry is preferred.

Skills gained

You will acquire transferable skills in python (applied to the analysis of molecular simulation trajectories) and command line scripting.

Investigating plant cell wall enzymes acting as molecular motors “without fuel”

Supervisor

Davide Mercadante

Discipline

School of Chemical Sciences

Project code: SCI052

Project

The plant cell wall (PCW) is a dynamic compartment separating plant cells from the outside world. It constitutes the cell's first line of defence against plant pathogens and it is at the centre of the morphological modifications of plant cells during different developmental stages of plants. Due to its inherent complexity, the PCW is shaped by dozens of carbohydrate-binding enzymes, which can slide along long carbohydrate chains such as pectin and cellulose. The mechanisms underlying sliding are unknown as is the specificity of several enzymatic isoforms.

Neverthless understanding such a mechanism is invaluable if we're to design strategies to protect plants from parasites or control their adaptabilities to different micro-environments.

In this project you will be running molecular dynamics simulations of carbohydrate-binding enzymes in complex with their substrate to understand how they process long chains of carbohydrates without the help of energetic cofactors. Intriguingly, this fact means these enzymes are effectively molecular motors “without fuel”.

Ideal candidate

For this project you won’t need any prior experience with molecular simulations or particular computer skills. Prior knowledge of protein chemistry is preferred.

Skills gained

You will acquire transferable skills in python (applied to the analysis of molecular simulation trajectories) and command line scripting.

Understanding how cancer-generating mutations hijack the conformational landscape and function of the main melanoma orchestrator

Supervisor

Davide Mercadante

Discipline

School of Chemical Sciences

Project code: SCI053

Project

If there would be a single protein that can be related to the onset of melanoma, this would be the transcription factor called MITF (microophtalmia-associated transcription factor).

Understanding the activity of MITF is thus the first necessary step to design strategies active against skin cancer.

Despite the large interest in finding solutions to fight the onset of melanoma and the importance of MITF in triggering the disease, little is known about this transcription factor.

The reasons for such a lack of knowledge are manifold, but should be addressed as a considerable challenge in understanding the role of intrinsic structural disorder in MITF.

While MITF features a small ordered domain that binds DNA, its regulation is prominently mediated by long stretches that do not fold stably into a well-defined secondary structure. (They look like highly mobile “tails” and are, for this reason, defined as intrinsically disordered regions). Because of their lack of structure, these regions are hard to study with conventional experimental techniques.

Intrinsically disordered proteins/regions are a relatively recent discovery and due to their high dynamics are hard to study with traditional structural biology techniques, such as crystallography.

Molecular simulations, on the other hand, are the gold standard in defining functional dynamics of polymers, and in this project you will be simulating the dynamics of MITF and its cancer-generating mutants, to understand how mutations modulate the dynamics of MITF and promote aberrant functioning of the protein, ultimately leading to the onset of diseases. This understanding is the first, crucial step for the design of inhibitors that can help individuals affected by melanoma and other MITF-related pathologies.

Ideal candidate

For this project you won’t need any prior experience with molecular simulations or particular computer skills. Prior knowledge of protein chemistry is preferred.

Skills gained

You will acquire transferable skills in python (applied to the analysis of molecular simulation trajectories) and command line scripting.

Behaviour of platinum electrodes at open circuit in grape juice and wine, compared to O2 content

Supervisor

Prof. Paul Kilmartin

Ext. 88324

Discipline

School of Chemical Sciences

Project code: SCI054

Project

The so-called redox potential of wine at a bright platinum electrode (with no current flowing) has a long history in enology. However, our own experiments have indicated that the measure provides only a broad indication of dissolved oxygen content, but little further information on wine redox status.

The experimental tests will include monitoring the redox potential and the dissolved oxygen content simultaneously during fermentation. Selective additions of ethanol to wines will be made and the redox potential response recorded. Prolonged exposure of wine to Pt at open circuit will be undertaken to check for acetaldehyde formation.

Compare commercial disposable PEDOT electrodes with home-made PEDOT for ascorbic acid oxidation

Supervisor

Prof. Paul Kilmartin

Discipline

School of Chemical Sciences

Project code: SCI055

Project

Past projects at the University of Auckland have shown that PEDOT is a reliable redox mediator for the analysis of small molecule antioxidants.

At our own PEDOT electrodes, signals for ascorbic acid are well separated from those due to uric acid or catechol-containing polyphenols, which appear at higher electrode potentials. However, the commercial PEDOT electrodes do not seem to perform so well, and a cross-comparison is needed, both with ascorbic acid and with other target antioxidants.

Characterisation of beverage antioxidants using cyclic voltammetry

Supervisor

Prof. Paul Kilmartin

Discipline

School of Chemical Sciences

Project code: SCI056

Project

The antioxidants present in beverages can be quantified and information provided about their reducing strength using the electrochemical technique of cyclic voltammetry. This technique has been developed at the University of Auckland to profile wines, fruit juices, teas, coffees, and milk. In this project, the voltammetry procedure will be applied to the antioxidants present in a series of alcoholic beverages, including beer and fortified drinks.

An examination of the most appropriate solvent for the measurement of the phenolic and other antioxidants present will be made, along with the electrode conditions needed to make a reliable quantification. Comparisons will be made with standard Food Science antioxidant assays, and a wide range of beverages of different strengths will be surveyed.

Synthesis of Novel inhibitors of Phospholipase C, an enzyme involved in cancer cell proliferation

Supervisor

Prof David Barker

Discipline

School of Chemical Sciences

Project code: SCI057

Project

Phospholipase C is a promising biological target for anticancer drug therapy with compounds binding to PLC showing marked growth inhibition of haematological tumour cells. We have recently discovered a class of compounds which are potent inhibitors of cell growth. Morphology and motility assays using triple negative breast cancer cell lines lead to the conclusion that PLC is the most probable bio-molecular target of these compounds however other important targets may be affected.

Role and ideal student

The student working in this project will be involved in the design (computation modelling), synthesis and biological testing of novel compounds to treat cancer. Students with an interest in organic or medicinal chemistry are encouraged to apply.

Synthesis of novel bio-based materials for water purification

Supervisor

Prof David Barker

Discipline

School of Chemical Sciences

Project code: SCI058

Project

One of the biggest challenges to New Zealand’s green and sustainable aspirations is pollution of waterways. Two of the main pollutants that are plaguing our freshwater is nitrates and heavy metals, high levels of which have been shown to cause significant health and environmental problems.

The primary aim of this project is to develop new filter materials using all natural, bio-based, compounds that will be able to purify water through the removal of damaging pollutants. This new technology will combine knowledge from areas of synthetic chemistry, polymeric materials and membrane science to produce a material capable of reducing toxins from fresh water.

The influence of the sensory and chemical fingerprint of foods during pairing

Supervisor

Dr Danaé Larsen

Discipline

School of Chemical Sciences

Project code: SCI059

Project

Little is known about why some foods "go together" and others don't. The working hypothesis is that food pairings exist based on the number of shared aroma compounds two foods have, however it is not as simple as this. Flavour/aroma compounds exist in food at different concentrations, are effected by cooking and processing and have differing levels of sensory perception during consumption.

We want to investigate whether it is enough that a food pairing shares a number of common flavour/aroma compounds or is it the type of flavour fingerprint (cumulative effect of the same flavour notes across different compounds) that make a successful pairing? Does when a particular flavour is perceived (throughout the sip/bite-swallow pathway) influence whether a pairing is successful or not? And can we use food pairing to learn to like disliked flavours?

The project will involve conducting sensory panels involving hedonic and dynamic sensory evaluation methods.

Iwi-Led Approaches to the Application of Psilocybin as a Mental Health Treatment in a Marae-Based Setting

Supervisor

A/P Dan Furkert

Discipline

School of Chemical Sciences

Project code: SCI211

Project

This summer project forms part of a wider research programme led by an iwi/hapū in Tairāwhiti, and includes contributions from Landcare Manaaki Whenua and ESR. The work will likely involve literature review of the chemistry and medicinal chemistry of the natural product, and experimental work to profile fungal sources and the stability of related metabolites.

It will suit a student with interests in natural products, medicinal chemistry and Māori health, and skills in literature survey and scientific writing.