Hong - Fluorescent probes, cell imaging, protein misfolding and neurodegenerative diseases
The Hong group is located in the La Trobe Institute for Molecular Science, La Trobe University, in Melbourne, Australia. We are passionate about developing next-generation chemical probes that facilitate selective labelling, visualisation, and comprehensive analysis of proteins, organelles, and other cellular components. By utilising these probes, we gain a deeper understanding of fundamental biological processes and their relevance to diseases.
Lab Head, Associate Professor Hong, was awarded the prestigious Le Fèvre Medal from Australian Academy of Science in 2022. Watch the video explaining the work of the Hong Lab.
Molecular reporters for measuring proteostasis capacity
Protein homeostasis (proteostasis) describes the maintenance of the proteome in a proper folded state by an extensive quality control network. Under normal proteostasis conditions, protein synthesis, proper folding and localisation, as well as the timely degradation and disassembly of abundant proteins are in balance. Perturbation of proteostasis often leads to the accumulation of misfolded proteins and aggregates, which has been linked to many neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s Diseases. Pharmacologic manipulation of the proteostasis network to improve its capacity is emerging as a new therapeutic strategy for these conditions.
Our laboratory has successfully developed a series of fluorogenic probes for quantifying and imaging intracellular unfolded protein loads, providing a measure of proteostasis capacity in cells. Furthermore, we have created fluorescent probes that target amyloid protein aggregates in vitro, enabling the detection of prefibrillar species during early stages of protein aggregation. These probes offer valuable insights into how cells maintain functional proteomes and respond to stress, holding promise for biomarker discovery in disease diagnosis and the development of effective treatment strategies.
Development of next generation probes for measuring autophagy
Autophagy (“self-eating”) is an evolutionarily conserved survival mechanism in living organisms during which intracellular components (‘cargo’) are identified and delivered to lysosomes for degradation. Basal autophagy plays a vital role in maintaining cellular homeostasis; dysregulation of autophagy has been found to associate with diseases ranging from neurodegeneration, early stage of cancers, cardiovascular disease to infectious disease, with different stages of autophagy being impaired. Research efforts have identified multiple molecular targets to rectify autophagy with the promise for therapeutic intervention. As autophagy is a multi-step process, it is important to identify and assess which stage of autophagy is affected by a modulator, to quantify the extent of the regulation and to draw a clear mechanistic picture. However, tools that allow real-time monitoring of the dynamics of autophagy, especially with quantitative readout, are still scarce and highly desirable. Our lab endeavours to develop next generation autophagy probes based on small molecules that are highly specific to autophagy, which can be used in live cells without the need of permeability or genetic modifications. These probes will be used to track the dynamic process of autophagy and measure its activity in cells and in vivo, with applications ranging from fundamental mechanistic studies, drug evaluation and screening, to disease diagnostics.
Development of bioanalytical tools for various applications
Leveraging our expertise in designing and synthesizing fluorescent probes, we are dedicated to developing cutting-edge bioanalytical tools. Our research focuses on creating novel fluorescent probes for the detection of urinary proteins, enabling effective monitoring of chronic kidney disease. Additionally, we aim to advance enzymatic activity detection in urine, cells, and soil samples through the development of innovative probes.
In order to analyse the intracellular environment, we have successfully developed a range of photostable organelle imaging agents. These agents facilitate precise tracking of cellular components such as mitochondria, lysosomes, endoplasmic reticulum (ER), nucleus, and the plasma membrane. Moreover, we have combined these agents with advanced fluorescence techniques to analyse critical intracellular parameters, including pH, viscosity, macromolecular crowding, and polarity. Our approaches allow for in-situ quantification of diverse physical parameters within live cells, enabling us to investigate their pivotal roles in driving fundamental biomolecular interactions, such as liquid-liquid phase separation and protein aggregation.
Meet the team
Specific detection and quantification of cardiolipin and isolated mitochondria by positively charged AIE fluorogens and method of manufacturing thereof: US Patent 10,113,968.
Aggregation Induced Emission Active Cytophilic Fluorescent Bioprobes for Long-Term Cell Tracking: US Patent 9,409,928.
Aggregation induced emission of fluorescent bioprobes and methods of using the same: US Patent 9,618,453.
Photostable AIE luminogens for specific mitochondrial imaging and its method of manufacturing thereof: US Patent 9,315,465.
Water-soluble AIE luminogens for monitoring and retardation of fibrillation of amyloid proteins: US Patent 9,279,806.
Aggregation-induced emission luminogens for metal ion detection: US Patent 9,228,949.
Water-soluble AIE luminogens for monitoring and retardation of fibrillation of insulins: US Patent 8,679,738.
Fluorescent water-soluble conjugated polyene compounds that exhibit aggregation induced emission and methods of making and using same: US Patent 8,129,111.
Fluorescent water-soluble conjugated polyene compounds that exhibit aggregation induced emission and methods of making and using same: US Patent 7,939,613.