Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, City East Campus, University of South Australia, Adelaide, SA 5001, Australia
Dr. Shane Hickey
Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, City East Campus, University of South Australia, Adelaide, SA 5001, Australia
Fluorescence microscopy has become a critical tool for researchers to understand biological processes at the cellular level. Micrographs from fixed and live-cell imaging procedures feature in a plethora of scientific articles for the field of cell biology, but the complexities of fluorescence microscopy as an imaging tool can sometimes be overlooked or misunderstood. This review seeks to cover the three fundamental considerations when designing fluorescence microscopy experiments: (1) hardware availability; (2) amenability of biological models to fluorescence microscopy; and (3) suitability of imaging agents for intended applications. This review will help equip the reader to make judicious decisions when designing fluorescence microscopy experiments that deliver high-resolution and informative images for cell biology.
Breast cancer (BC) is one of the leading causes of death from cancer in women; second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented.
The state-of-the-art for metal ion sensing by GQD probes is reviewed. The field is discussed, along with the challenges to determine specific mechanisms of interaction. This understanding is highly desired to develop selective GQD-metal ion sensors.
Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular compartments.
1 December 2018 in European Journal of Medicinal Chemistry