Professor Conan Fee from UC’s School of Product Design has established a large multi-disciplinary research team, spanning three tertiary institutions and Callaghan Innovation to tackle ground-breaking research on 3D-printed porous media for chemical and process engineering.
Engineers today still largely approach the design and manufacture of fluid-solid contacting systems in ways that reached maturity 50-100 years ago, relying on tubes, fins, plates and randomly packed particles within vessels. Professor Fee’s research team’s work to date has shown that using 3D-printed triply periodic minimal surfaces (TPMS) offer significant advantages over existing heat exchanger and porous bed designs. However, the lack of engineering science and computational tools required to design the 3D-printed structures is preventing their use in real-world applications.
In this project, funded for five-years by the Ministry of Business, Innovation and Employment (MBIE)'s Endeavour Fund, Professor Fee brings together chemical engineers, mechanical engineers, biologists, physicists, computer scientists and materials scientists to:
- Understand flow in TPMS structures under different flow regimes and create new insights into the heat and mass transfer performance of TPMS structures. This will enable definition of new design equations for TPMS structures;
- Create computer-aided design tools to enable optimised design and print of large, finely-structured objects; and
- Demonstrate proof of concept prototypes for high-value market niches in different materials.|This project will vastly improve outcomes from chemical and process engineering design and will generate transformational business potential for New Zealand.
A significant proportion of therapeutic proteins are glycoproteins, i.e. proteins with sugars attached, and these sugars are vital for their function/activity. The current methods for manufacturing glycoproteins are extremely expensive, time consuming, and invariably produce inseparable mixtures of products, only a fraction of which may display the desired activity.
Our aim is to develop a totally new and novel approach to making glycoproteins that will enable us to produce pure products, precisely select the structure of the carbohydrate component to optimise the product’s function, and to significantly reduce the overall manufacturing costs by increasing production efficiency. Our vision is to create an NZ-based commercial vehicle to develop and commercially exploit this production process, both alone and in partnership with multinational biotechnology companies.
There is an urgent need for cheap and effective screening devices that can be used in non-clinical settings. We have developed peptide fibrils that reversibly form hydrogels, creating “stimuli responsive hydrogel membranes”. Using this technology, we will develop a novel assay platform with broad application due to its simplicity, ease of use, and temperature tolerance. This will allow screening tests to be undertaken in remote and adverse environments by relatively untrained users.
We will produce a proof-of-concept assay device for glycated haemoglobin for use in diabetes monitoring to test our technology. Future development of the platform will seek to develop simple assay test solutions to address water testing issues in remote areas and "pen-side" testing for animal diseases.
It is possible to think of cells, in a metaphorical sense, as castles with moats that separate them from their surrounding environment. In this scenario, moats are membranes and the guards controlling essential supplies allowed into the castle are specialised transporter proteins. This may be a helpful metaphor but, of course, the reality is much more complex and these transporter proteins – buried within cell membranes – are much harder to study than any castle guard!
Our goal is to understand how these transporter proteins work. Our focus is a particular family of proteins called TRAP transporters. We hope to unravel the molecular details of how these transporters move essential nutrients across the bacterial cell membrane and into the cell. As well as providing fundamental insights into molecular activities, this knowledge will drive a better understanding of bacterial pathogenicity and colonisation, and underpin the future development of new antibiotics to combat harmful bacteria.
This innovative research program will develop a technology platform to target therapeutic agents to a specific cellular organelle: the lysosome. The ability to specifically deliver drug molecules to the lysosome is essential for the development of new and improved therapies for a range of >50 currently incurable diseases, including the lysosomal storage disorders.
We will target a cellular receptor that internalises molecules that carry a specific carbohydrate tag, called mannose-6-phosphate (M6P), and then delivers them to the lysosome. The precise attachment of M6P-tags to therapeutic agents will mean that they are trafficked by this receptor’s action, and so represents a highly specific way of targeting them to the lysosome. We will develop a unique method to attach M6P-targeting tags to bioactive agents in a completely controlled fashion, using world-leading synthetic chemistry and biocatalysis. Exquisitely selective synthesis will produce M6P-tags with optimal structure for processing by the receptor. Enzyme engineering will produce biocatalysts that irreversibly attach these tags to bioactive molecules.
In vitro cellular imaging studies will then demonstrate that the M6P-tagged bioactives are efficiently transported to the lysosome. Realisation of our approach will enable the development of new lysosomal-targeted therapies, and the potential treatment of >50 incurable diseases.
Fungi and fungi-like organisms known as oomycetes are important players in the cycle of life as they decompose dead and decaying organic matter. Through this crucial role in the nutrient cycle they influence the wellbeing of human populations on a large scale. However, while many fungi and oomycetes are benign, some pathogenic species cause disease in plants and animals. Recent infamous examples include Kauri Dieback and Myrtle Rust. To combat these disease causing species, it is important to understand how they locate and infect their target. For example, spores of certain fungi use electric fields present in the roots of trees to detect and navigate towards them. Once at the target, spores of pathogenic fungi and oomycetes begin to germinate, sending out shoots that physically invade the tissue of the target, sometimes leading to its death.
Our aim is to establish the antifungal properties of new compounds, plants and other species for the development of novel treatments. To do so, we are developing lab-on-a-chip devices to further understand how fungi and oomycetes find targets and physically invade them. The devices will include arrays of electrodes to determine how spores locate tree roots, and whether roots can be protected using external electric fields. They will also include force-sensing micropillars to help determine the internal mechanisms by which the fungi and oomycetes generate the mechanical forces they use to penetrate their targets. If the factors that underlie all these mechanisms can be determined, this may impact how we address the many diseases and infections that occur due to pathogenic fungi and oomycetes.
The binding of a ligand to one site on a protein can influence binding and/or catalysis at a second site. This phenomenon, termed protein cooperativity, is a vital regulatory mechanism that underpins life. Cooperativity offers ways for proteins to modulate their functions and adapt metabolic processes to changes in the environment. We know that proteins utilise movements of their atoms to communicate binding events over long distances; however, the precise molecular mechanisms by which cooperativity regulates protein activity are seldom well defined.
Here, we aim to use an enzyme that displays cooperative behaviour, MenD from Mycobacterium tuberculosis, as a model system to unravel the underlying communication networks. We have already visualised key steps of the catalytic cycle of MenD by crystallography and we now aim to define the molecular mechanisms by which its binding sites communicate. We will use an integrative approach, with a variety of structural and biophysical techniques, to build a picture of the different factors that underlie communication. This will enhance our understanding of protein cooperativity, provide insight into how a vital enzyme from a human pathogen is regulated, and build a knowledge base for future drug design and protein engineering efforts.
The ecological drivers impacting community development and bacterial infection of plants are largely unknown. Plant leaves are excellent systems to study these drivers: most leaf colonising bacteria can be cultured and can be inoculated onto germfree, laboratory-grown plants. When the bacteria carry fluorescent proteins they can be visualised on leaves, in real-time, using microscopy. This is facilitated by the flatness of leaves, although leaves have a significant topography at the microscale.
To build a predictive understanding of colonisation processes on leaves, we propose using “synthetic” bacterial communities to investigate spatial community development and early stages of infection in planta. To do so, we will investigate how overlap in nutrient utilisation between bacteria impacts community spatial structure and how community structure impacts on secondary colonisation success. Furthermore, we will unravel the impact of the host plant on bacterial communities by using artificial copies of the leaf surface topography. This will unveil if leaf topography alone is sufficient to drive community development or if plant exudates determine what is colonising leaf surfaces and where. This project will deliver comprehensive insights into how bacteria colonise plant leaves and how plants impact on community spatial structure.
We have various ongoing projects aimed at developing advanced tools to examine food structures and investigate important interactions. These include studying the molecular interactions in milk and in oil bodies found in seeds, and investigating the effects on proteins during food-processing and digestion, such as those found in meat, milk and bread. We hope that by learning from the structures inherent in natural foods and how foods are digested and assimilated, we will be able to create high-value healthy foods with novel structures.
Led by Manaaki Whenua - Landcare Research, the Beyond Myrtle Rust research programme is supported by the Ministry for Business, Innovation and Employment's Endeavour Fund, involving researchers and iwi from across Aotearoa and Australia. 'Beyond myrtle rust: towards ecosystem resilience' will focus on boosting ecosystem resilience by running ground-level interference of myrtle rust. The programme will centre on filling critical gaps in current efforts to manage myrtle rust, and develop a better understanding of the pathogen dynamics, drivers, and function, with a view to creating resilience within diseased landscapes.
Protein crystallisation is an essential method for determining protein structures, used globally by academic teams, pharmaceutical companies, and the biotechnology industry. Protein crystallisation experiments on the International Space Station have illustrated the benefits of a microgravity environment for producing high quality protein crystals that are otherwise intractable on Earth. Unfortunately, the current options for Kiwi researchers to conduct research in microgravity environments are quite limited.
To expand opportunities for researchers in New Zealand and around the globe to use microgravity for essential protein crystallisation experiments, we are developing a nanosatellite-based space biology laboratory for crystallising proteins in low Earth orbit. With the cost of small satellite development and deployment decreasing and the availability of launches increasing, there now exists a cost-effective platform with which to use these satellites for advanced biotechnological research as well as commercial R&D applications
The development of humans and animals starts from a mass of stem cells that change, eventually, into all the different cells that make up the structures of an adult organism. Stem cell biologists have been trying to direct stem cells to differentiate into specific cell types , however, current processes are time-consuming and expensive and do not guarantee the differentiation of stem cells into certain cell types of interest.
Azadeh aims to investigate the use of cell-imprinted substrates – 3D replicas of live cells or tissues imprinted onto a rigid material – for culturing stem cells. These cell-imprinted surfaces, combined with other material properties, will allow Azadeh to create a cell-culture substrate similar to cells’ natural environment. This will not only lower the cost of directed stem cell differentiation, but also increase the accuracy of the differentiation process and the range of differentiated cells produced.
There is growing concern about the emergence of bacterial strains showing resistance to all classes of antibiotics commonly used in human medicine. Therefore, there is an urgent need to develop alternatives to conventional antibiotics for use in the treatment of both humans and food-producing animals. Bacteriophage-encoded lytic enzymes (endolysins), which degrade the cell wall of the bacterial host, are potential alternatives to antibiotics. Their potential for development is furthered by the prospect of bioengineering, aided by the modular domain structure of many endolysins which separates the binding and catalytic activities into distinct subunits. These subunits can be rearranged to create novel, chimeric enzymes with optimized functionality. Furthermore, there is evidence that the development of resistance to these enzymes may be reduced compared with conventional antibiotics.
Plant leaves are a major habitat for bacteria. However, the surface of a leaf is a challenging place to live. In contrast, the interior of a plant contains comparatively abundant nutrients and mild environmental conditions that allow microbial pathogens to thrive and cause disease. Bacterial pathogens of plants are unable to directly penetrate the leaf surface on their own; they must gain entry into the plant through either natural openings such as stomata, or via wounds. The molecular basis of how bacteria navigate between these vastly different habitats remains poorly understood.
Motile bacteria are attracted by certain chemicals and repelled by others, a behaviour termed chemotaxis, which enables them to navigate towards favourable conditions. Our research will explore the ‘what, how and why’ of bacterial chemotaxis in the phyllosphere. Longer-term, these insights may lead to novel plant disease management strategies.
The future of food is predicted to include a variety of protein-rich foods for consumers, including those produced by culturing animal cells in fermenters (termed cellular agriculture). It is expected that new hybrid foods will also emerge, offering increased consumer choice. Dr Domigan’s new project will build on her existing research in the area, exploring the interactions between plant proteins and cultured animal cells, since this is central to developing successful hybrid foods. The results of this research will be essential to inform regulatory bodies and policy-makers about safety and efficacy and will provide New Zealand industry with the scientific understanding of this new transformational technology.
Established in May 2019, Sustainable is Attainable is a project launched by Venture Timaru (the economic development agency for the Timaru region) in collaboration with the University of Canterbury. The Timaru District and the wider South Canterbury area has a rich, productive primary sector, including small family food businesses, national and multi-national companies exporting food and beverages around the world. One of the biggest challenges identified by these businesses is managing their waste streams and by-products. Many of these end up as very low value products or in landfill. Subsequently, BIC and the New Zealand Product Accelerator are supporting a number of research projects that aim to add value to waste streams and by-products.
3D printing holds exciting promise in personalised formulations and is rapidly taking over the pharmaceutical industry. The ability to tune the release profiles of specific molecules in a formulation allows tailoring to individual needs of a system making the technology suitable for many other formulations that cannot be prepared easily by other manufacturing methods. Tailored formulations for agriculture or conservation-related applications have not yet been explored using 3D printing as a tool. We aim to identify and optimise methods to utilise 3D printing with biodegradable natural material to develop smart formulations for agriculture and conservation.
We are looking to engineer and evolve enzymes to perform polymerisation reactions using unnatural monomeric building blocks, and to engineer biomolecules (biopolymers) to create high-value polymeric materials. The project spans research at the molecular level and chemical biology (e.g. using the brand new ion mobility-mass spectrometer within BIC at UC) all the way to applications, with line-of-sight to creating polymers in applications from food, packaging, to high-tech materials.
With technological advancements in rapid prototyping and 3D bioprinting, biocompatible hydrogel materials known as ‘bioinks’ can now be fabricated using these emerging technologies. However, little is understood about the optimal parameters to print a wide range of these materials. This project focuses on investigating these optimal printing parameters based on material properties of the bioink. After optimizing printing protocols, the bioinks will be charactered by their mechanical properties as well as their biological behaviors. One application for 3D printed hydrogels is tissue scaffolds. Using fundamental information about the printing parameters and material properties, a 3D-printed hydrogel structures can be optimized using tissue engineering to repair spinal cord injury.
Although there is increased consumer demand for plant-based protein alternatives, many of the current options sourced from plant seeds lack the functionality of animal based proteins. Attempts at replicating the taste and texture of meat often fail to deliver as the plant-based substitutes have different characteristics to the original options. As a key enzyme in photosynthesis, Rubisco is both involved in fixing carbon dioxide as well as representing the main soluble protein component in plant leaves.
Our project aims to improve agricultural production via two different mechanisms:
- We aim to improve photosynthetic efficiency in crops (particularly wheat), by enabling rapid identification of natural variants of the Rubisco enzyme that have faster catalytic rates and are more efficient at capturing carbon dioxide.
- Develop protocols for the large scale extraction and purification of Rubisco from leaves, so that we can demonstrate its potential as a plant based protein for use in the food and cosmetics industry.
Many recovery programmes using intensive management to recover wild populations of endangered birds, including iconic taonga species unique to Aotearoa New Zealand, report issues with fertility. Selecting appropriate individuals for breeding in these programmes is vital, as the inclusion of individuals with reduced fertility impedes species recovery. Current selection methods are inadequate because the genomic basis of infertility is unknown and standard approaches for detecting it are not reliable.
Our project will leverage new and existing genomic resources with an innovative cytogenetics approach to identify the genes and/or gene regions underlying maladaptive reproductive traits like infertility. We will use these discoveries to revolutionise existing breeding selection tools by providing a pathway to simultaneously maximise genomewide diversity and minimise the impact of maladaptive reproductive traits.