Centre for Chemistry and Drug Discovery - Earmarked
Development of venom-derived blood-brain barrier shuttles
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
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 models and assays, proteomics, peptide chemistry, molecular biology and pharmacology. 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. Anticipated benefits include technological innovations relevant to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.
*Qualifies for an Earmarked Scholarship.
Engineering high-efficiency light-driven synthetic biology
Principal Advisor: Prof Ben Hankerman (IMB)
This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
Every two hours Earth receives enough energy from the sun to power our global economy for a year. The capture and use of this energy are essential to power a sustainable zero CO2 emissions future, increase international fuel security and build advanced light-driven industries as part of an expanding circular bioeconomy.
Over 3 billion years, photosynthetic microorganisms have evolved to tap into the huge energy resource of the sun and use it to synthesise a diverse array of biomolecules that collectively form biomass. This photosynthetic capacity can be adapted to create clean fuels for the future such as hydrogen and an array of high-value biomolecules.
This PhD project is focused on the development of high-efficiency light-driven single cell green algae (microalgae) cell lines that can produce hydrogen fuel from water as well as high-value molecules using advanced genetic “plug-and play” molecular biology techniques.
Building on extensive foundational work, the project will involve the design of expression vectors, cell transformation and screening, creation of specific point mutants and gene knockouts using CRISPR and their characterisation (e.g. photosynthetic physiology, H2 production). The project may extend to technoeconomic analyses of scaled up designs and lab scale validation of the proposed industrial processes.
*Qualifies for an Earmarked Scholarship.
Investigating the role and therapeutic potential of the oxytocin receptor in prostate cancer
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
Associate Advisor: A/Prof Jyotsna Batra (QUT)
This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.
Prostate cancer is the second most frequent malignancy in men worldwide, causing over 375,000 deaths a year. When primary treatments fail, disease progression inevitably occurs, resulting in more aggressive subtypes with high mortality. This project focuses on the oxytocin/oxytocin receptor (OT/OTR) signalling system as a potential new drug target and biomarker to improve prostate cancer management and patient survival. Anticipated outcomes include a better understanding of OT/OTR’s role in prostatecancer 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, some bioinformatics skills (e.g., ability to implement statistical tests in R/Python and program scripts to automate analyses) 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 prostate cancer models.
*Qualifies for an Earmarked Scholarship.
Modulating protein-protein interactions in disease
Principal Advisor: Prof David Fairlie (IMB)
This project requires candidates to commence no later than Research Quarter 1, 2025, which means you must apply no later than 30 September, 2024.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
Most diseases are mediated by protein-protein interactions, often fleeting contacts between large protein surfaces too shallow to sequester conventional small molecule drugs. This project will design and develop classes of new compounds at and above size limits of conventional drugs to modulate more difficult protein-activated receptors that are largely targets without drugs. To do this, the candidate will first truncate one of the binding partners to a smaller peptide and optimise its structure, composition, protein affinity, and functional potency in order to modulate the protein-protein interaction that leads to disease. This will require knowledge and skills in peptide chemistry, solid phase synthesis, HPLC purification, spectroscopy (NMR, MS, CD), and an ability and motivation to modify peptides into small bioavailable molecules using organic synthesis techniques. Some knowledge of cell biology and enzyme assays would be an advantage, as would knowledge of NMR spectroscopy. The long term goal is to design new compounds and profile them for effects on genes/proteins/cells/rodent models of immunometabolism, inflammatory diseases and cancer. Outcomes will include new knowledge of protein-protein interactions in disease; greater understanding of drug targets, disease mechanisms and effectiveness of new drug action; patentable methods and bioactive compounds; and new experimental drug leads to new medicines for preclinical development towards the clinic.
*Qualifies for an Earmarked Scholarship.
Molecular design of drugs to fight chronic human diseases and environmental pests
Principal Advisor: Dr Conan Wang (IMB)
Must commence by Research Quarter 3, 2025.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
An excellent opportunity for a PhD candidate to explore cutting-edge technologies for design of bioactive proteins to fight chronic human diseases or environmental pests. A motivated individual will be immersed in a leading research institute and international team at UQ, supported by an Australian Centre of Excellence and nationally funded research programs.
Development of drugs for human benefit, whether to cure human diseases or safeguard our food resources and environmental assets, must begin with the design of bioactive lead molecules. This research program will investigate platform technologies for engineering of novel proteins, which are actively pursued by many emerging biotechnology industries. The candidate will choose one of the following major application areas of national importance.
- Next-generation anti-cancer drugs
- Antimicrobial agents to fight infection
- Bio-friendly drugs to control agricultural pests
- Natural proteins to prevent crown of thorns starfish outbreaks
A typical project will involve use of protein structure to design new drugs. The candidate could choose to use either computational design tools or molecular libraries to screen massive numbers of drug leads. This often followed by characterisation of structure and activity using biophysical, biochemical and/or biological assays.
*Qualifies for an Earmarked Scholarship.
Photocontrollable probes to study neuropeptide-mediated memory formation
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as innovative chemistry strategies and novel molecular probes to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations of relevance to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.
*Qualifies for an Earmarked Scholarship.
Targeting strategies for drug design
Principal Advisor: Prof David Fairlie (IMB)
This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
Selective binding of small molecules with proteins underpins most drug discovery. However, while a compound can be devised to interact with a single protein, this cannot drive the molecule into a specific location where functional modulation of the target protein only at that location is desired for therapy. Instead, designed compounds usually bind to the protein wherever it is expressed in the body and this can be deterimental to normal healthy physiology. This project will investigate a number of promising new approaches to directing protein-binding compounds to specific compartments of cells and organisms. It will require a combination of organic synthesis, medicinal chemistry, molecular modelling and chemical biology. The new approaches will be tested and optimised with the goal of inhibiting or activating desired proteins in specific compartments in order to modulate disease-causing protein functions without altering normal healthy physiology. Achieving these aims will require enthusiasm, a high degree of self-motivation, lateral thinking, strong chemical knowledge and hands-on skills in organic synthesis (solution and solid phase), NMR characterisation (including 2D NMR structure analysis), HPLC purification, mass spectrometry, and computer modelling. Some knowledge of enzyme assays and cell biology would be an advantage. The long term goal is to design new compounds and profile them for selective effects on target genes/proteins/cells/rodent models of inflammatory diseases and cancer. Outcomes will include new knowledge of protein function in disease; greater understanding of medicinal and organic chemistry in drug design, drug targeting, mechanisms and effectiveness of drug action; patentable methods and bioactive compounds; and new experimental leads to new medicines for development towards the clinic.
*Qualifies for an Earmarked Scholarship.
Tuning the activating stimulus of voltage-gated sodium channels
Principal Advisor: Dr Angelo Keramidas (IMB)
This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.
This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.
This project will investigate how voltage-gated sodium channels, which are proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. The overall aim is to study how molecular probes (venom peptides) and structural parts of these ion channels affect the local biophysical environment of the ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that activates them (cell membrane voltage).
This project will use natural and modified peptides that are derived from venoms of different species, such as spiders and ants to probe and manipulate the functional properties of an ion channel that is critically important to the function of the nervous system.
The conceptual knowledge gained from this project would advance our understanding of a fundamental physiological process and facilitate the development of drugs that regulate ion channel function, such as antiepileptics, analgesics and insecticides.
*Qualifies for an Earmarked Scholarship.
Understanding how blood vessels in the brain are formed
Principal Advisor: Dr Rosemary Cater (r.cater@uq.edu.au)
Associate Advisor: Dr Anne Lagendijk (a.lagendijk@imb.uq.edu.au)
The human brain comprises ~650 kilometres of blood vessels lined by brain endothelial cells, which supply the brain with oxygen and essential nutrients. The growth of cerebral blood vessels begins early in development via a process called sprouting angiogenesis. Despite its importance, the molecular mechanisms underlying brain angiogenesis and formation of the blood-brain barrier are poorly understood. It has recently been demonstrated that the gene Flvcr2 is critical for blood vessels to grow in the brain, and last year we discovered that the protein encoded by this gene (FLVCR2) transports choline – an essential nutrient – across the blood brain barrier and into the brain. This project will utilise biochemical techniques and structural biology (cryo-EM) to investigate what other molecules may regulate this transport process, and how choline regulates angiogenesis in the brain.
*Qualifies for an Earmarked Scholarship.