Novel secreted proteins involved in obesity and type 2 diabetes

A signal sequence trap was utilised to identify secreted proteins which were differentially expressed in key metabolic tissues associated with obesity and type 2 diabetes. Decorin and periostin were identified and functionally characterised as novel secreted proteins associated with the pathophysiology of these conditions.

Identification of proteins that interact with the copper transporter ATP7B

In this study proteins were identified that interact with the key liver enzyme, ATP7B that is affected in the copper toxicity disorder Wilson disease. Detailed characterisation of the interaction with glutaredoxin and dynactin subunit p62 contributes significantly towards our understanding of the mechanisms that regulate copper balance in the body.

The evolution of organelle division proteins in diverse eukaryotes

The evolutionary distribution of chloroplast and mitochondrial division proteins has been investigated, gleaning new insights to the evolution of organelle division: specifically the use and features of FtsZ and dynamin-like proteins. Additional novel proteins that are potentially involved in mitochondrial division have been identified in Dictyostelium discoideum.

The role of copper transport proteins in the small intestines

Physiological copper homeostasis involves striking a balance between absorption and secretion. ATP7A was identified at the trans-Golgi network but relocalized to vesicles under copper exposure in the intestine. This suggests that ATP7A may be a rate limiting step in intestinal uptake of copper.

Metabolically important secreted proteins in Psammomys obesus

A new adipokine, chemerin, was identified and its expression in P. obesus and in humans suggests that it is an important contributor to the development of obesity and type 2 diabetes. Polymorphisms within the CHEMERIN gene further support its involvement in obesity and type 2 diabetes.

Dissecting the role of SOCS proteins using zebrafish

Suppressors of cytokine signalling (SOCS) proteins are negative regulators of the JAK-STAT pathway which is perturbed in certain disease states including cancers and inflammatory diseases. This thesis ascertained the suitability of zebrafish as an alternative animal model to study the SOCS proteins which established new and additional roles during development.

An aspartyl protease directs malaria effector proteins to the host cell

Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.

Industrial biotechnology for the production of proteins/enzymes for a sustainable future

Worldwide emergence of Industrial biotechnology (IB) is providing opportunities to produce enzymes/proteins with variety of industrial/therapeutic applications. In transitioning the Australian economy towards a sustainable future, Federal government identified the development of IB pathway which would ensure increased productivity, enhanced sustainability, health, safety and reduced environmental footprint. The presentation will revolve around specific stories that drives Deakin University newest technology platform which applies biology and fermentation in an integrated way to play a crucial role in developing cost-effective technologies for the development of molecules that can benefit pharmaceutical and food industry in regional Victoria and Australia in general. The talk will also highlight specific examples where new products like recombinant rhamnosidase (an enzyme used for the production of flavonoids with health benefits) and ribosome inactivating proteins (detected in medicinal plants which possess RNA N- glycosidase activity that depurinates the major rRNA, thus damaging ribosome in an irreversible manner and arresting protein synthesis) would be made available through bioprocessing.

Ribosome inactivating proteins (RIPs) : a promising candidate for industrial biotechnology

The ribosome inactivating proteins (RIPs) from plants possess RNA N- glycosidase activity that depurinates the major rRNA, thus damaging ribosomes in an irreversible manner and arresting protein synthesis. RIPs are presently classified as rRNA N-glycosidase in the enzyme nomenclature (EC 3.2.2.22) and do exhibit other enzymatic activities such as ribonuclease and deoxyribonuclease activities. RIPs have been shown to manifest anti-tumor, anti-viral and anti-microbial activities. RIPs are detected in some medicinal plants but the yields are insufficient to warrant their availability to conduct clinical trials thus limiting its therapeutic potential. Here, an approach based on "bioprocess development" shall be discussed that may enhance the yield of RIPs. It is anticipated; with the involvement of “Industrial biotechnology” the eventual availability of RIPs in large quantities shall be accomplished.