Centre for Cellular and Molecular Biology

Copper in health and disease

Copper is an essential nutrient metal involved in a wide variety of physiological and pathological processes. It has become clear that copper regulatory pathways are corrupted in conditions that include neurodegenerative diseases and cancer, leading to dysregulated copper levels. The molecular basis of the link between copper and disease is being investigated.

Investigating the therapeutic potential of copper nanomaterials

This project aims to investigate the biology of copper nanomaterials (NMs) and their application to the treatment of diseases (such as cancer and neurological disease), where the manipulation of internal copper levels may have therapeutic value.

Investigating metal aberrations in senescence, from basic science to therapeutic enquiry

We are developing ways to exploit metal aberrations to selectively target and destroy senescent cells without harming primary (normal) cells. The main aims of this research are to understand the cellular mechanisms and pathways leading to divalent metal accumulation during senescence and to evaluate metal-complexes as selective therapies for the clearance of senescent cells and hence mitigate age-related pathologies.

Copper-ionophores as a potential treatment for cancer

Elevated copper in both malignant tissue and serum is emerging as a genuine ‘universal feature’ of certain cancers. This research builds upon our discovery that copper-ionophores can selectively target and rapidly destroy cancerous cells without harming primary (normal) cells. An ionophore by definition transports specific metal(s) into cells often allowing them to become bioavailable. We are evaluating the therapeutic potential of copper-ionophores in the treatment of mouse models of human cancer.

Can copper be used to selectively kill prostate cancer cells?

The primary aim of this research is to understand the cellular mechanisms and pathways leading to copper accumulation and copper-ionophore sensitivity in cancer. We hypothesize that: (i) cancerous cells accumulate intracellular copper early during their development, that (ii) aberrations in the expression profile of copper-homeostasis proteins underpins copper accumulation and that (iii) our custom-made copper-ionophores selectively and effectively kill actual human cancerous tissue.

Zinc in health and disease

Zinc deficiency is a public health problem that affects some communities including pregnant and breast-feeding women and newborn babies. Lack of zinc affects the immune system, impairs wound healing and may cause growth retardation, if severe. Projects are underway to investigate the role of zinc transporters in zinc homeostasis and the association of impaired zinc homeostasis in human diseases.

Zinc and omega-3 interactions

Dietary intake of omega-3 fatty acids, especially DHA, can reduce the severity of depression and neurodegenerative disorders. The mechanism of this protective effect is not clear but may be through altered zinc fluxes. We brought together a multidisciplinary team, with expertise in cell biology, omega-3 fatty acids metabolism and nanosomes chemistry to utilize nanoliposomes for the targeted delivery of DHA to neuronal cells. Our ultimate goal is to provide a safe and effective system to improve the DHA supplements.

Understanding how cancers spread around the body

A major problem in treating cancers is that the cancer cells may have spread around the body and cannot be targeted by radiation or chemicals, without normal cells being affected. We have developed a cell culture model of the human breast that is enabling us to unravel the different stages in cancer progression that may lead to the development of new anti-cancer strategies.

Understanding the molecular and cellular mechanisms of excitotoxic neuronal death

Excitotoxic neuronal injury is well documented to be a disease mechanism contributing to the pathophysiology of stroke (hypoxic-ischaemic injury), traumatic brain injury, Alzheimer's and motoneurone diseases. The role of cell cycle-associated protein kinase in excitotoxic neuronal death is being investigated and targeted gene delivery into primary cerebral cortical neurons using lentiviral vector mediated overexpression and knockdown functional studies is employed in this research study.

The function and regulation of the Set1C histone methyltransferase

Histone modifying enzymes regulate diverse processes that occur in association with chromatin. We performed extensive yeast two-hybrid screening in order to identify novel cellular roles for the Set1C chromatin-modifying enzyme. We identified the molecular mechanisms, which link chromatin modification of histone H3 lysine 4 to the formation of double strand DNA breaks, to initiate the process of meiotic recombination.

Co-translational protein complex formation

Multi-protein complexes constitute some of the most relevant molecular units of cellular function but it remains mysterious how eukaryotic cells manage to assemble with precision hundreds of different complexes in the crowded cytoplasmic compartment that produces thousands of nascent proteins at the same time. Assembly of protein complexes can be initiated on nascent proteins as they emerge from the ribosome. We are currently investigating the functional significance of co-translational protein interactions.

The role and regulation of alternative polyadenylation in health and disease

Pre-mRNA 3’ end formation is an essential RNA maturation step that impacts on virtually all aspects of mRNA function where the process adds a tail of approximately 250 adenosines to the 3’ end of mRNA and determines the length of the 3’ Un-Translated Region (3’UTR), which is targeted by a large number of regulatory factors. Control of 3’UTR length via alternative Polyadenylation (APA) is an important mechanism to control gene expression. We are interested in the regulation of APA and how it is integrated with cellular signalling pathways.

Evolution of Organelle Division

We study the molecular cell biology of mitochondrial and chloroplast division. While we that know that these two organelles arose from bacteria, we know little about how they are replicated and distributed at cell division. These are basic questions of biology and answers to them will help us understand how these respiratory and photosynthetic machines have been retained by cells for millions of years. Our model organisms are protists, such as the amoeba Dictyostelium and unicellular algae.

Atmospheric release and dispersal of biological particles (bioaerosols) from plants and fungi, and their impacts on human health.

Grass pollen allergens are a major trigger of seasonal allergy, causing both hayfever and asthma symptoms.  Airborne particles are collected from the atmosphere each day using sophisticated, techniques to detect pollen allergens in air samples, and levels of respirable allergen are correlated with hospital admissions for asthma. Results are being compared both locally and internationally to gauge the role of weather instability on pollen rupture and subsequent asthma risk. Asthma risk forecasting models can then be refined based on weather forecasts, and seasonal and daily pollen counts.

The properties of striated muscle change through growth and development and as a result of disease states or physiological challenges.

The major focus of this work is to determine what changes occur at the level of the muscle proteins and also functionality at the single fibre level using the skinned fibre technique using both vertebrate and invertebrate models.

Biomolecular electrochemistry or bioelectrochemistry is the study and application of biological electron transfer processes and deals with the transformation of molecules triggered by electron transfer from or to an electrode and/or using of molecules, enzymes, bacteria, cells, dispersed in the solution or attached to the electrode surface to accelerate and optimize an electrochemical reaction.

Current projects include:

• Understanding the electron-transfer mechanisms of acidithiobacillus ferrooxidans and its application to bioleaching processes
• Electrochemical characterization of Cyanobacteria and its application to bioremediation
• Microbial electrochemical cells, i.e. conversion of organic matter to electricity and commodities
• Development of enzymatic and microbial electrochemical biosensors
• Development of Immunosensors
• Supported lipid bilayers as a model system to understand the effect of analytes on cellular membranes

Comparative animal physiology

This research focusses on cardiovascular regulation, osmoregulation, and more recently, the control of appetite and energy balance, and uses a diverse range of animal models. The primary theme is to reveal the physiological control systems in animals from diverse environments in order to understand how they evolved and contribute to the maintenance of homeostasis.

The research uses a range of animal models from fish to mammals, and a suite of molecular, cellular and physiological techniques, which permits an integrated analysis from gene to function.

Local and international collaborations include:

• evolution of natriuretic peptide systems in vertebrates
• nitric oxide control systems in vertebrates
• control of water balance in desert rodents.

Evolution of crustacean enzymes

Function, evolution and adaptation of cellulase and hemicellulase enzymes in crustaceans This project aims to identify the genes involved in the production of cellulase and hemicellulase enzymes within crustacea and describe the evolution, adaptation and function of these enzymes.

Mental hyperaccumulators

This research focuses on developing and applying a range of analytical techniques to study the chemistry of some unique organisms. A particular focus is on metal hyper-accumulating plants and oil producing algae. These exceptional organisms have a range of applications, the hyperaccumulating plants have the potential to clean-up heavy metal contaminated soils. The lipid producing algae could be utilised as a renewable source of biofuels. Understanding the underlying chemistry driving these unique traits is crucial for their real world application.

Bioremediation

In collaborative projects with partners in China and India, we have utilised plants for extracting heavy metals from contaminated soils. This entails an understanding of the molecular mechanisms of metal accumulation by plants and fungi. Studies are also underway to establish how cyanobacteria, an organism that has been on the planet for over 3 billion years, can tolerate metal stress, and the role of cellular heavy metal transport systems in metal homeostasis.

Plant pathogens

The plant pathogen, Phytophthora., is an oomycete (P. cinnamomi is the causative agent of dieback and P. infestans of potato blight), and is thus more closely related to brown algae than it is to the fungi that it has been traditionally grouped with. We are searching for novel proteins in Phytophthora that may act as useful targets for the future control of this cancer of the plant world.

Plant-insect interactions

Taxonomy, biology and DNA bar-coding of invertebrates including gall midges from the Family Cecidomyiidae is being undertaken on gall midges, as few have been formally described worldwide. This research has significant practical applications as members of the Family Cecidomyiidae are host-plant specific and known to impair the sexual reproduction of native plants.

The co-evolution of plant-insect interactions - particularly the relationship between Asphondylia (Diptera: Cecidomyiidae) midges and the fungus lining the galls they induce is also being studied.