Centre for Chemistry and Drug Discovery - Projects List

Principal Advisor: A/Prof Nathan Palpant (IMB)

Associate Advisor: Dr Andrew Mallett (IMB); Dr Sonia Shah (IMB), Dr Mikael Boden (UQ School of Chemistry and Molecular Biosciences)

Industry partnership opportunities: HAYA Therapeutics; Maze Therapeutics

Despite strong vetting for disease activity, only 10% of candidate new drugs in early-stage clinical trials are eventually approved. Previous studies have concluded that pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. This project will take advantage of increasing clinical disease data, rapid growth in GWAS datasets, drug approval databases, and innovative new computational methods developed by our team. The overall goal is to develop unsupervised computational approaches to understand what genetic models and data are most predictive of future drug successes. Underpinning this work, the project will build and implement computational and machine learning methods to dissect the relationships between genome regulation, disease susceptibility, genetic variation, and drug development. The project will not only reveal fundamental insights into genetic control of cell differentiation and function but also facilitate development of powerful unsupervised prediction methods that bridge genetic data with disease susceptibility and drug discovery. Students with background/expertise in computational bioinformatics and machine learning are ideal for this work. Informed by clinical, computational, and cell biological supervisory team, the project will have an opportunity to engage with diverse international companies through internships and collaborations to facilitate co-design of these methods for uptake in industry discovery and prediction pipelines.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Hana Starbova (IMB)

Associate Advisor: Prof Irina Vetter (IMB; UQ School of Pharmacy); Dr Raelene Endersby (Telethon Kids Institute)

Treatments such as radiotherapy and chemotherapy for childhood and adult brain cancers save many lives. However, they also cause long-term debilitating adverse effects, also termed "late effects", such as pain, cognitive disabilities and sensory-motor neuropathies. Currently, no effective treatments are available, and brain cancer survivors are forced to live with long-term disabilities.

Animal models are important for the understanding of disease pathology and for preclinical testing of novel treatment strategies. However, currently there are no appropriate animal models available for the testing of late effects of cancer therapy.

To address this gap, this PhD project aims to develop in-vivo animal models of cancer therapy-induced late effects and to test the efficacy of novel treatment strategies. This project forms a foundation for future clinical studies.

Animal handling and behavioural assessments in rodents are vital for this project.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Nathan Palpant (IMB)

Associate Advisor: Prof Jennifer Stow (IMB); Prof Brett Collins (IMB); A/Prof Markus Muttenthaler (IMB)

Industry partnership opportunities: Infensa Bioscience

This project focuses on strategies to prevent organ damage associated with ischemic injuries of the heart. There are no drugs that prevent organ damage caused by these injuries, which ultimately leads to chronic heart failure, making ischemic heart disease the leading cause of death worldwide. Globally, 1 in 5 people develop heart failure, with annual healthcare costs of $108 B. Our team has discovered a new class of molecules, acid sensitive ion channels, that mediate cell death responses in the heart during ischemic injuries like heart attacks. This project will study the function of acid sensing channels using cell and genetic approaches. We will use innovative new drug discovery platforms to find new peptides and small molecules that inhibit acid channel activity. Finally, the project will use disease modelling in stem cells and animals to evaluate the implications of manipulating these channels using genetic or pharmacological approaches to study the implications in models of myocardial infarction. The candidate will benefit from background/expertise in cell biology and biochemistry. Collectively, this project will deliver new insights, tools, and molecules that underpin a key area of unmet clinical need in cardiovascular disease. The project will be supervised by experts in drug discovery, cell biology, and cardiovascular biology and includes opportunities for internships with industry partners such as Infensa Bioscience, a new spinout company from IMB developing cardiovascular therapeutics for heart disease.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences)

The blood-brain barrier controls the transfer of substances between the blood and the brain, protecting us from toxic compounds while allowing the transfer of nutrients and other beneficial molecules. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. The project will involve cell culture, blood-brain barrier assays, proteomics, peptide chemistry, NMR structure determination, and molecular biology and pharmacology. The candidate should have a degree in biochemistry, pharmacology or cell biology, good hands-on laboratory skills and strong ambition and work ethics. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences. 

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Zeinab Khalil (IMB)

Associate Advisor: Prof Rob Capon (IMB); Prof Ian Henderson (IMB)

Australia’s marine territory is rich with vast microbial diversity that remains unexplored. These microbes harbour the next generation of environmentally responsible resources and products (new molecules). Knowledge of microbial chemical diversity can significantly advance our understanding to enhance the discovery of small molecules that can be used as bioactive products, such as anti-infective, antiparasitics, and crop protection fungicides.

This project seeks to develop advanced and optimised methods in UPLC-QTOF-MS/MS molecular networking, to rapidly, cost-effectively, reproducibly and quantitatively map the small molecule and peptide chemical diversity of taxonomically and geographically diverse Australian marine microbes and microalgae, including fresh and processed biomass, biorefinery fractions and outputs, and formulated marine bioproducts – to advance the discovery and development of valuable new marine bioproducts. 

The successful candidate will join a Marine bioproducts cooperative research centre (MB CRC) funded project and multi-disciplinary team supported by microbiological and genomic sciences; they will gain skills and experience in analytical, spectroscopic and medicinal chemistry – to inform and inspire the discovery of future medicines.

Applicants must have a strong background with outstanding grades in organic chemistry and an interest in learning multidisciplinary biosciences. 

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Andrew Walker (IMB)

Associate Advisor: A/Prof Nathan Palpant (IMB)

Jellyfish cause some of the most serious envenomation syndromes of all animals, responsible for >77 deaths in Australia to date and many more around the world. Two jellyfish of interest are the box jellyfish Chironex fleckeri, whose venom targets the heart to kill in as little as two minutes; and its much smaller relative the Irukandji jellyfish Carukia barnesi, envenomation by which causes a long-lasting and painful ordeal. Jellyfish also represent an ancient group of venomous animals with unique biology different from all other venomous animals. Despite this, little is known about jellyfish toxins, how they work, or how we might design therapeutics or novel treatments to ameliorate their effects. This project would involve combining state-of-the-art techniques to isolate and characterise jellyfish toxins, test them using a range of bioassays, and assess possible agents to protect from their harmful effects.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Zeinab Khalil (IMB)

Associate Advisor: Prof Ian Henderson (IMB); Prof Rob Capon (IMB)

Microbes have been a new promising source of modern medicines, including antibiotics (e.g. penicillin) and immunosuppressants (e.g. sirolimus) and well as agents to treat cancer (e.g. adriamycin) and cardiovascular (e.g. statins) disease, as well as many more. Recent advances in genomics offer the prospect of exciting new approaches to discovering the next generation of medicines hidden within the Australian microbiome. 

To this end in 2020 we launched Soils for Science (S4S) as an Australia wide citizen science initiative, designed to engage the public, to collect 10's of thousands of soil samples from backyards across the nation, from which we will isolate 100's thousands of unique Australian microbes.

This project will annotate the S4S microbe library to prioritize those that are genetically and chemically unique. These will be subjected to cultivation profiling, and fermentation, followed by chemical analysis to isolate, identify and evaluate new classes of chemical diversity. 

The successful candidate will join a multi-disciplinary team where, supported by microbiological and genomic sciences, they will gain skills and experience in analytical, spectroscopic and medicinal chemistry – to inform and inspire the discovery of future medicines. 

Applicants must have a strong background with outstanding grades in organic chemistry, and with an interest in learning multidisciplinary biosciences. 

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Loic Yengo (IMB)

Over half a million women die from breast cancer annually (>3,000 in Australia), affecting one in eight women. It is therefore important to pursue new drug targets to improve therapy and patient survival. The oxytocin/oxytocin receptor (OT/OTR) signalling system plays a key role in childbirth, breastfeeding, mother-child bonding and social behaviour. It is also involved in breast cancer, where it modulates tumour growth, including subtypes such as triple-negative breast cancer that remain difficult to treat.

This project will investigate OT/OTR’s role in tumour growth and metastasis and assess its therapeutic potential in breast cancer management. It will focus on the OTR-specific tumour growth and metastasis pathways and on the development of therapeutic leads to reduce tumour growth. Anticipated outcomes include a better understanding of OT/OTR’s role in breast cancer and new therapeutic leads for an alternative treatment strategy.

The candidate should have a degree in biochemistry, pharmacology or cell biology, good hands-on laboratory skills and strong ambition and work ethics. The candidate will be involved in genetic/bioinformatic analysis, cancer cell signalling assays, chemical synthesis of OT ligands, GPCR pharmacology and characterisation of therapeutic leads in breast cancer models.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences)

Venoms comprise a highly complex cocktail of bioactive peptides evolved to paralyse prey and defend against predators. The homology of prey and predator receptors to human receptors renders many of these venom peptides also active on human receptors. Venoms have therefore become a rich source for new neurological tools and therapeutic leads with many translational opportunities.

This project covers the discovery, chemical synthesis, and structure-activity relationship studies of venom peptides, with a specific focus on gastrointestinal stability and drug targets in the gut. Venom peptides are known for their disulfide-rich frameworks supporting secondary structural motifs not only important for high potency and selectivity but also for improved metabolic stability. While primarily studied for their therapeutic potential as injectables, this project will break new ground by investigating evolutionarily optimised sequences and structures that can even withstand gastrointestinal digestions, thereby providing new insights for the development of oral peptide therapeutics targeting receptors within the gut. These therapeutic leads will have enormous potential for the prevention or treatment of gastrointestinal disorders or chronic abdominal pain.

The candidate should have a degree in synthetic chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, NMR structure determination, CD studies, structure-activity relationship studies, gut stability assays, and receptor pharmacology.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: Dr Sebastian Furness (UQ School of Biomedical Sciences)

The advent of highly-processed, calorie-rich foods in combination with increasingly sedentary lifestyles has seen a rapid rise in overweight and obesity. 60–80% of populations in developed countries are overweight or obese, and over three million deaths each year are attributed to a high body mass index. Obesity is also a risk factor for diabetes, hypertension, cardiovascular disease, kidney disease, and most kinds of cancer. This has a clear impact on life expectancy, with predictions that this generation will be the first to have a shorter life expectancy than the last. Despite this enormous socioeconomic impact, treatment options are limited.

Our research groups are interested in the role of the gut peptides GLP-1 and CCK in regulating appetite and satiety. A subset of GLP-1 mimetics are already successful treatments for obesity, however, compliance is low as they are injectables. The project will focus on the development of orally active mimetics. The project will also develop molecular probes to facilitate the study of the GLP1 and CCK1 receptors in the context of appetite regulation across the gut-brain axis.

The candidate should have a degree in chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and a desire to drive the project. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, cell culture, gut stability assays, cell signalling and receptor pharmacology.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: Prof Alpha Yap (IMB)

Inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS) affect 10–15% of the Western population, having a substantial socio-economic impact on our society. The aetiology of these disorders remains unclear, and treatments focus primarily on symptoms rather than the underlying causes.

Our research group is pursuing innovative therapeutic strategies targeting gastrointestinal wound healing and protection to reduce and prevent such chronic gastrointestinal disorders. This project focuses on the trefoil factor family, an intriguing class of endogenous gut peptides and key regulators for gastrointestinal homeostasis and protection. The project will focus on the chemical synthesis of the individual members and molecular probe and therapeutic lead development to advance our understanding of their mechanism of action and explore the therapeutic potential of these peptides for treating or preventing gastrointestinal disorders.

The candidate should have a degree in chemistry, biochemistry, pharmacology or cell biology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, NMR, cell culture, wound healing assays, gut stability assays, cell signalling and receptor pharmacology.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Emily Goodall (IMB)

Associate Advisor: Prof Ben Hankerman (IMB); Prof Ian Henderson (IMB)

Friend or Foe, bacteria are powerhouses at the centre of many important biotechnological processes, but also the disease-causing agents of many infectious diseases. Understanding the fundamental processes of a bacterial cell is key to understanding (1) how to harness these organisms for biotechnological gain and (2) how to target them in the treatment of an infection. Using the model organism, Escherichia coli, we aim to develop a method for identifying protein-protein interactions in a high throughput format. The methodology developed in this project will enable total proteome screening and has implications for studying both fundamental cell physiology as well as the potential for studying protein-drug interactions in vivo. After development, the technology will be validated by screening for chemical inhibitors of protein-protein interactions.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Prof Tim Mercer (AIBN); Prof Mark Walker (IMB)

An opportunity exists for a PhD position in vaccine engineering. Vaccines are one of the most effective health care interventions but remain a challenge for many diseases, and in particular intracellular pathogens such as malaria where T cell responses are particularly desirable. We have been exploring novel  approaches to rationally design an effective vaccine against challenging disease targets. By taking advantage of recent advances in genomic sequencing, proteomics, transcriptional profiling, and molecular immunology, we have discovered unique targets of T cell responses or antibody response. This project will test these antigens as vaccine candidates by assessing immunogenicity, protective capacity and biological function using different vaccine platforms. By designing an effective vaccine from genomic data, this project is expected to result in significance advances in vaccinology as well as immunology, with important public health outcomes.

Subject areas: Immunology, Vaccinology, Molecular immunology, Malaria, Vaccine engineering, Vaccine design

Eligibility: Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required. 

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Glenn King (IMB)

Associate Advisor: A/Prof Lata Vadlamudi (UQ Centre for Clinical Research)

There are more than 65 million people currently living with epilepsy, and more than 1/3 are resistant to anti-seizure medications (ASMs). For these latter patients, new efficacious ASMs are urgently required. This project will focus on development of biologic drugs for treatment of genetic epilepsies caused by aberrant expression of a voltage-gated ion channel. We are specifically interested in: (i) Dravet syndrome, which is caused by aberrant function of the voltage-gated sodium channel Nav1.1, and (ii) KCNH1 epilepsy, caused by gain-of-function mutations in the voltage-gated potassium channel Kv10.1, which was first described here at the Institute for Molecular Bioscience. This project brings together the expertise of the King lab in venoms-based peptide-drug discovery and development, and the clinical expertise of Prof. Vadlamudi in treatment of genetic epilepsies. Lead compounds will be isolated from arthropod venoms, the best known source of ion channel modulators. Prof. King’s lab has access to the largest collection of arthropod venoms in the world (>500 species). Lead compounds will be tested in brain organoids produced from patient-derived stem cells as well as in vivo rodent models of Dravet syndrome and KCNH1 epilepsy.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Fernanda C Cardoso (IMB)

Associate Advisor: Dr Jean Giacomotto (QBI/Griffith); Prof Glenn King (IMB)

Neurodegenerative diseases are caused by progressive loss of neurons, leading to dementia, motor dysfunction, paralysis, and death. Investigation of ion channels in central neurons unravelled clusters of voltage-gated ion channel subtypes playing a key pathological role in the pre-symptomatic stages of neurodegenerative diseases. Venoms are an exceptional source of peptides modulating ion channels with higher potency and selectivity than poorly efficacious drugs used in the treatment of neurodegeneration.
This project involves systematically interrogating venoms using computational approaches, high throughput in vitro and in vivo screens, venomics and pharmacology to discover venom peptides that selectively modulate ion channels in central neurons and therefore have the potential to prevent central neurodegeneration.
This is a multidisciplinary project in drug discovery utilizing venoms and other natural repertoires as main sources of bio-active molecules. PhD scholars will develop skills in computational biology, manual and automated whole-cell patch clamp electrophysiology, ex vivo tissue electrophysiology, in vivo screen in zebrafish, high performance liquid chromatography, mass spectrometry, recombinant expression, peptide synthesis, amongst other state-of-the-art methods and techniques. Students will author papers and be involved in writing and preparation of figures for research publications from their work.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Irina Vetter IMB)

Associate Advisor: Dr Richard Clark (UQ School of Biomedical Sciences)

Voltage-gated sodium channels are well-validated analgesic targets, with loss-of-function mutations leading to an inability to sense pain, but otherwise normal physiology and sensations. However, efforts to mirror these genetic phenotypes with small molecule inhibitors have highlighted that both selectivity over ion channel subtypes and mechanism of action are key considerations for the development of safe and effective analgesics. 

This project will leverage the exquisite potency and selectivity of peptide sodium channel modulators from venoms for the rational development of novel, safe and effective molecules with analgesic activity. 

Students will gain experience with peptide synthesis, patch-clamp electrophysiology, sensory neuron culture, microscopy and in vivo behavioural assays to tackle the global problem of unrelieved chronic pain with innovative molecules targeting peripheral sensory neuron function.

*Qualifies for the Global Challenges Scholarship.