Highlights

Professor David Craik is a structural biologist who travels the world discovering new molecules in plants and animals. His area of expertise is peptides (mini-proteins). He is looking for peptides that could be effective treatments for a range of diseases or have useful applications as environmentally friendly agri-chemicals. He particularly likes to discover something in nature and then use molecular design to improve on it.

Professor Craik is best known for discovering a family of peptides with a unique circular structure, which he aptly named cyclotides. Cyclotides are super stable, which makes them desirable as drug leads. By re-engineering the structure of other peptides to mimic cyclotides, he is making potent and specific peptides orally active – creating the perfect drug. He is known internationally as the founder of this field of research. 

He was the first person to take a peptide from a cone snail, a natural conotoxin, and re-engineer its structure to make it cyclic. By improving the strength of the molecule, he created a natural painkiller 100 times stronger than the current market leader gabapentin, and potentially with lower side effects. The drug is currently showing great promise in animal trials. This natural painkiller is the first time an orally active drug has resulted from an animal venom. In other applications Professor Craik’s methodology led to the commercialisation of an environmentally friendly insecticide.

Professor Craik is known internationally for his work in peptide-based drug design and sought after as a conference speaker on the topic. 

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Associate Professor Irina Vetter has a strong background in neuropharmacology, pain models, toxinology and high-throughput screening. Currently her primary research interests lie in the fields of peripheral pain mechanisms, target identification, biodiscovery of venom peptide ion channel modulators and analgesic drug discovery.

Associate Professor Vetter has always been fascinated by how we perceive the world around us, in particular, the role of sensory neurons in the body. Sensory neurons are an intricate network of nerve cells that convert external stimuli from the environment into messages within the body, like pain. Her research is demystifying the different pathways that contribute to pain in various disease states. She is using biomedical research and pharmacology to develop pain treatments from venoms and toxins.

Associate Professor Vetter is an ARC Future Fellow and Deputy Director of the Centre for Pain Research at The University of Queensland. She is a registered pharmacist and has worked in hospital as well as community pharmacy. She obtained her PhD in 2007 from the School of Pharmacy, and conducted postdoctoral studies as an NHMRC postdoctoral fellow under Prof Geoffrey Goodhill at the Queensland Brain Institute and under Prof Richard J Lewis at the Institute for Molecular Bioscience in the areas of axon guidance and venom peptide pharmacology

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Paul Alewood graduated from the University of NSW before moving to the University of Calgary for his PhD. His early research interest was in classical organic chemistry, but the discovery in the mid 1970s of encephalins – short-chain amino acids produced in the body that have a similar effect to morphine – triggered an interest in protein and peptide chemistry.

He moved to Queensland, attracted by the state’s healthy populations of dangerous marine animals – cone snails, sea snakes and stone fish, to name a few. Such animals offer vast potential in the treatment of chronic pain, as their venom contains thousands of small peptides that target sensory nerve receptors.

He is the author of more than 300 publications and was a prime mover in establishing the Melbourne-based peptide company, Auspep, and Xenome, a spin-off biopharmaceutical company from the University of Queensland. More recently, he was a foundation scientist at Betabiotics, a joint venture company between IMB and CSIRO, and the founder of Elacor, a joint venture between the University of Queensland and the Baker Heart Research Institute, Victoria.

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Professor Rob Capon is a natural products chemist. He is a master of interrogating the molecular diversity of the natural world and applying it to society’s most pressing social and economic problems. He goes out into the natural world, detects biologically active molecules from living things, then isolates, identifies and evaluates them. Most importantly, he is committed to finding a use for them. His mantra for commercialization is ‘forced failure', in other words, “if you can break it, you won’t make it”. With the enormous untapped potential of natural products, he doesn’t like to waste time. He works quickly to “break or make” hypotheses, to focus resources on those molecules that are worthy of investment.

Professor Capon leads a group of researchers that are responsible for assembling a world-class molecule library, which along with the Australian collection of microbes housed at IMB, is used to discover new drugs. For Professor Capon, the most rewarding aspect of his work is the ability to dip into the molecular resource in the Australian environment, extract the chemistry and use it to improve our understanding of the natural world, and solve important problems.

He applies his research methodology to human health, animal health, crop protection, and environmental protection. He collaborates broadly in each of these areas.

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Professor David Fairlie is internationally known for his research contributions in the fields of medicinal chemistry, organic chemistry, biological chemistry and in several disciplines in biology (pharmacology, virology, immunology, neurobiology, biochemistry). He has had strong research programs in chemistry, biochemistry and pharmacology continuously funded by the Australian Research Council (ARC) since 1991 and the National Health and Medical Research Council (NHMRC) since 1995. He was awarded prestigious fellowships from the ARC, in the form of an Australian Professorial Fellowship (2002-2006) and an Australian Federation Fellowship (2006-2011), and from the NHMRC, in the form of a Senior Principal Research Fellowship (2012-2016 and 2017-2021). He has held numerous research grants in chemistry, biochemistry, pharmacology, virology, immunology, parasitology, neurobiology and oncology; including 15 multimillion dollar grants from industry and governments. He has served on academic and industry advisory panels, company boards, and research grant panels both in Australia and overseas. He collaborates with some of the world's largest pharmaceutical companies.

Professor Fairlie has >300 publications (h index >60; >14,000 citations; >35 cites per article; >30 articles >100 citations) and presents 5-10 invited plenary and keynote lectures around the world each year. He is also well known in the international pharmaceutical arena, having consulted to multiple big pharma on protease inhibitors, GPCR modulators, protein and peptide mimics, drug design and discovery, and pharmacology. He has been involved in four startup companies in Australia and the USA.

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Professor Glenn King is a biochemist and structural biologist whose expertise lies in translating venom-derived peptides into human drugs and bioinsecticides. His lab maintains the most extensive collection of venoms in the world, which includes venoms from more than 600 species of venomous spiders, scorpions, centipedes and assassin bugs.

Professor King’s primary focus is on the development of drugs to treat three pervasive nervous system disorders: chronic pain, epilepsy, and stroke. His lab is working closely with several pharmaceutical companies to develop drugs for clinical use.

Professor King has also charted new territory in the field of agriculture by developing venom peptides as eco-friendly bioinsecticides. Vestaron Corporation, the company that he founded, will begin selling these bioinsecticides in the U.S. market in 2017.

Mentorship is important to Professor King, and he is enthusiastically committed to training the next generation of biological scientists. To date he has trained 30 PhD students and 24 postdoctoral scientists, with 10 lab alumni having gone on to independent academic positions.

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Associate Professor Mark Smythe is a medicinal chemist. His expertise lies in transforming interesting molecules into high-value medicines.

His methodology for translating academic discoveries into commercially viable companies has achieved great success. He founded biotech company Protagonist Therapeutics in 2001, which is now a publicly listed company with several compounds in human clinical trials and several others sold to pharmaceutical partners. He and his team worked for 15 years to develop an approach to replace injectable drugs with pills. They took high potency, highly selective peptides that are traditionally broken down quickly by the body, and made them stronger. So, diseases that used to require ‘big-molecule’ injections we can now treat with a ‘constrained peptide’ pill. This has several advantages to the patients and addresses unmet medical needs of various diseases

Associate Professor Smythe has always had a focus on applied research, making things. He studied a Bachelor of Science with Honours in Townsville. He wanted a PhD that was applied, so he took at position at Biota with a focus on Influenza. After working in the US, he accepted a position at the then 3D Centre in Queensland, now the Institute for Molecular Bioscience (IMB). At IMB he uses his expertise to translate discoveries into new drug candidates.  

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Highlights

Professor David Craik is a structural biologist who travels the world discovering new molecules in plants and animals. His area of expertise is peptides (mini-proteins). He is looking for peptides that could be effective treatments for a range of diseases or have useful applications as environmentally friendly agri-chemicals. He particularly likes to discover something in nature and then use molecular design to improve on it.

Professor Craik is best known for discovering a family of peptides with a unique circular structure, which he aptly named cyclotides. Cyclotides are super stable, which makes them desirable as drug leads. By re-engineering the structure of other peptides to mimic cyclotides, he is making potent and specific peptides orally active – creating the perfect drug. He is known internationally as the founder of this field of research. 

He was the first person to take a peptide from a cone snail, a natural conotoxin, and re-engineer its structure to make it cyclic. By improving the strength of the molecule, he created a natural painkiller 100 times stronger than the current market leader gabapentin, and potentially with lower side effects. The drug is currently showing great promise in animal trials. This natural painkiller is the first time an orally active drug has resulted from an animal venom. In other applications Professor Craik’s methodology led to the commercialisation of an environmentally friendly insecticide.

Professor Craik is known internationally for his work in peptide-based drug design and sought after as a conference speaker on the topic. 

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Markus Muttenthaler received his BSc in technical chemistry (2001) and his MSc in organic chemistry and technology (2004) from the Vienna University of Technology. In 2005 he obtained a PhD scholarship to join Paul Alewood’s laboratory at The University of Queensland. He then received training in peptide chemistry and was involved in the discovery, design and development of therapeutics based on bioactive venom peptides. He earned the best PhD thesis award from the Royal Australian Chemical Institute, and the Dean’s award for outstanding higher degree thesis.

As a postdoc, Dr Muttenthaler continued to expand his chemical skills repertoire and developed an interest in oxytocin and vasopressin research. Two Marie Curie Fellowships enabled him to join the Dawson lab at the Scripps Research Institute in California, distinguished for the invention of native chemical ligation, a technique that revolutionised chemical synthesis of proteins, and the Albericio lab at the Institute for Research in Biomedicine Barcelona, renowned for its innovative advancements in combinatorial and peptide chemistry.

In 2015, he was recruited back to IMB as an ARC DECRA fellow to establish his neuropeptide research program. His recent achievements earned him the IMB Industry Fellow Award as well as the prestigious Miklos Bodanszky Award for peptide-based drug research.

Research overview

Dr Muttenthaler’s interdisciplinary background has proven highly valuable to research efforts to understand fundamental human physiology and pathology. His current focus is on developing molecular probes, diagnostics and therapeutics to help in the treatment of disorders such as neuropathic pain, cancer, autism, gastrointestinal disorders and neurodegenerative diseases.

“Most of our leads come from nature,” said Dr Muttenthaler. “Venoms form a rich source of bioactive compounds, as they comprise highly complex cocktails of potent peptides that can paralyse prey or defend against predators. The similarities of prey/predator receptors to human receptors make these venom peptides excellent leads for the development of neurological tools and therapeutics.”

A recent addition to his research program is the discovery of novel gastrointestinal wound healing modulators.

“Humans continuously produce specific peptides that have a critical role in protecting and restoring our gut epithelium – the single layer of cells that protects us from pathogens.”

Dr Muttenthaler said that when the production of these gut peptides is not working properly, we become more susceptible to pathogens. This can lead to gastrointestinal inflammation that further resolves into chronic disorders such as Irritable Bowel Syndrome and Inflammatory Bowel Disease (around 15 per cent of the population are affected by these disorders).

“For someone suffering from gastrointestinal disorders, or who is undergoing chemotherapy that is harsh on the gut, the idea would be to supply an agent to protect or even restore that important epithelial layer.

“We’re interested in not just treating the symptoms, but the underlying root of the problem,” he said.

Research projects

Peptides are key mediators in many biological functions and understanding of their interaction with target proteins is fundamental to unravel the underlying mechanism of diseases. Over the years, an increasing number of bioactive peptides from animals, plants, and bacteria have been characterised, with the overwhelming realisation that these molecules often show better therapeutic performance than their human counterparts, particularly in terms of in vivo stability.

Our main research efforts situated in the field of Neuropeptide Research focus on the exploration and translation of these vast and untapped natural libraries towards the development of useful research tools and therapeutics. Solid-phase peptide synthesis, the main tool to access these compounds, is a powerful technology for the assembly and chemical modification of these highly chiral and structurally complex peptides.

Venoms to Drugs

Venoms comprise a highly complex cocktail of bioactive peptides evolved to paralyze prey and defend against predators. Homology of prey/predator receptors to human receptors render these venom peptides also active on human receptors and they have become a rich source for neurological tools and therapeutics. Our group is involved in the discovery, synthesis and structure-activity relationship studies of these venom peptides with the goal to develop novel probes for neuroscientists as well as therapeutic drug leads.

Oxytocin and Vasopressin Research

The oxytocin and vasopressin signalling system regulates many fundamental physiological processes such as reproduction, water balance, cardiovascular responses and complex social behaviour. It is also a high-profile target for autism, schizophrenia, stress, depression, anxiety, cancer and pain. Our group is particularly interested in creating a complete molecular toolbox to study this signalling system as well as in discovering novel therapeutic leads for autism, pain, gastrointestinal disorders and breast cancer.

Neuropeptides and long-term Memory Formation

Memory is probably the single most important brain process that defines our personality and gives us the sense of individuality. Emotional events often cause the generation of strong memories that exist for many years, yet the underlying mechanisms are still poorly understood. Neuropeptides are key players in regulating emotions and have been associated with long-term memory formation. Our group is involved in the development of advanced molecular probes to understand how neuropeptides can influence long-term memory formation.

Gastrointestinal Disorders

The gastrointestinal epithelium is a major physical barrier that protects us from diverse, and potentially immunogenic or toxic content. A damaged epithelium results in increased permeability to such content, thus leading to inflammation, uncontrolled immune response, and diseases, such as irritable bowel syndrome and inflammatory bowel disease that affect 10-15% of the population. Our group is involved in the identification and validation of novel drug targets and therapeutic strategies that can protect or repair this important barrier in order to prevent or treat such disorders.

Engagement and impact

Dr Muttenthaler is internationally recognised for his expertise in venom peptide drug discovery, neuropeptide research and his pioneering methods in peptide chemistry. His work focuses on developing tools that facilitate basic fundamental research as well as drug discovery. He recently received the prestigious Miklós Bodanszky Award for his outstanding contributions for peptide-based drug research.

Peptides are key mediators in many biological functions and understanding of their interaction with target proteins is fundamental to unravel the underlying mechanism of diseases. Over the years, an increasing number of bioactive peptides from animals, plants, and bacteria have been characterised, with the overwhelming realisation that these molecules often show better therapeutic performance than their human counterparts, particularly in terms of in vivo stability.

Our main research efforts situated in this field of Chemical Biology focus on the exploration and translation of these vast and untapped natural libraries towards the development of useful research tools and therapeutics. Solid-phase peptide synthesis, the main tool to access these compounds, is a powerful technology for the assembly and chemical modification of these highly chiral and structurally complex peptides. This complexity is also responsible for their remarkable selectivity and potency as well as for their low side effect profile observed in the clinic.

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