Gruber Lab overview

 

Plant peptides as modulators of human and invertebrate neuropeptide receptors

Circular plant peptides share similarities with some neuropeptides (e.g. oxytocin), and acts on their receptor. The oxytocin/vasopressin signalling system is important for reproduction, development, and behaviour as well as water homeostasis. To elucidate the natural function of cyclotides, we aim to characterise the pharmacological properties and biological effects of invertebrate receptors and their modulation by cyclotides. The notion that plants produce molecules to target invertebrate receptors is extremely appealing and will enhance knowledge about fundamental biological processes of plant-animal ecology. Furthermore, we aim to establish pharmacological screens that elucidate novel cyclotides as modulators (agonists/antagonists) of human peptide G protein-coupled receptors (GPCR) to test whether these nature-derived peptides are useful to design GPCR therapeutics.

Supported by ARC, Future Fellowship FT140100730

Individual function and social role of oxytocin-like neuropeptides in ants

Some insects possess neuropeptides (inotocins) that are related in sequence and function to the mammalian oxytocin/vasopressin system. These phylogenetically ancient peptide hormones have a broad physiological function, affecting mainly water homeostasis and reproduction, but are also important regulators of learning, memory and complex social behaviours. They therefore play vital roles in both individual physiology and group living of social animals. We have teamed up to study both aspects in ant societies, in which we have recently discovered components of this signalling system for the first time in social insects, as the honeybee noticeable lacks this system. Ants therefore provide a unique model system to study not only the physiological role of this neuropeptide system for individual ants, but also how it may affect group living in eusocial insects in comparison to the well-studied societies of mammals, including humans. We will combine genome data analysis, biochemical and pharmacological characterization and gene knock-down experiments to study the diversity and functionality of this unexplored neuropeptide system in ant physiology. We will further perform behavioural observations to elucidate how these neuropeptides may affect colony reproductive patterns and social interaction networks. By this overarching approach we aim to uncover the role of this neuropeptide system in social insects, both at the individual and society level. 

Supported by WWTF - Life Science LS13-017

Circular peptides as novel therapeutic agents for autoimmune diseases

Multiple sclerosis (MS) is a serious chronic condition for which there is no cure. Current drugs can reduce disease symptoms but are often associated with severe side effects. Cyclotides are plant-derived peptides that are considered an ideal template for designing novel drugs due to their biological stability and oral activity. We previously isolated and characterise, orally active, circular peptides with immunosuppressive properties to treat MS. Our project aims to synthesize novel peptides, study the signalling mechanism and targets proteins involved with the observed immunosuppressive activity and therapeutic effects in mice. Studying the molecular mechanisms of cyclotides and designing improved cyclotide mimetics to treat MS in cell-based and animal models will contribute significantly to the field immunopharmacology. Ultimately, the outcomes of this study may yield novel therapeutic targets and lead compounds to treat and ameliorate MS in humans.

Development of cyclotide drugs to treat MS by Cyxone

Circular plant peptides as novel modulators of insect immunity

The biological function of plant compounds if often unclear, but they may target physiological processes involved in predator devitalization. We isolated widely distributed circular plant peptides that supress immune cell proliferation in human cells. This project will determine the ability of these peptides to modulate immunity in insects, allowing elucidating their role in herbivore defence. 

Supported by the University of Queensland ECR Grant.

Characterization of uterotonic plants and compounds

The use of uterotonic plants and preparations for a variety of childbirth-related medical conditions is widespread amongst traditional medicines and many women in rural areas of developing countries rely on herbal remedies during pregnancy, childbirth and postpartum care. To explore the safety and efficacy of indigenous uterotonic plants and their use by pregnant woman and traditional birth attendants, it is imperative to identify and describe the active ingredient(s) and their pharmacology. Our research aims to, identify novel cyclotide-containing plants with uterotonic activity and assess their efficacy and safety in the preparation of herbal treatments for childbirth-related medical conditions.