Category Archives: UA

Super-resolution volumetric imaging

11 December 2018:

The Australian Research Council (ARC) has announced funding for a super-resolution imaging facility that will be the first of its kind in Australia.

The facility brings together a consortium of multidisciplinary researchers from leading Australian Universities, Institutes and Research Centres (including CNBP) to develop new capacities for materials science, photonics devices, engineering, and neuroscience, microbial and cardiovascular research.

At its core the A$3.0m ARC LIEF project will enable scientists to study the inner workings of cells in their native environment. This represents a step change from currently imaging isolated 2D cells cultured in a petri dish to future research that will reveal subcellular structures and cell-to-cell communications in 3D tissue in real time.

The National Volumetric Imaging Platform, as it is known, will be installed, maintained and operated by the Institute for Biomedical Materials and Devices (IBMD) at the University of Technology Sydney (UTS) and the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) at RMIT University in Melbourne. This project is scheduled to be completed in late 2019.

UTS Professor Dayong Jin, Lead Chief Investigator of the project, said that the facility will give scientists a “new way to decode the complexities of life science machinery.”

“High-resolution imaging of the large volume of single cells and functional navigation of their interactions will allow researchers to drop into a ‘street view’ and observe the details of intercellular ‘live traffic’,” he said.

A/Prof Brant Gibson, Co-Deputy Director and RMIT node director of CNBP said, “I am very excited to lead the RMIT University node of the National Volumetric Imaging Facility and to work in collaboration with Jin Dayong, the UTS node and all of our collaborative institutional partners. This facility will enable us to image deeper within biological samples than we ever been able to before, with nanoscale resolution and extraordinary bandwidth stretching from the near-UV (400nm) well into the infrared (1650nm) spectrum.”

Prof Mark Hutchison, Professor at the Adelaide Medical School and Director of the CNBP at the University of Adelaide said, “This is an exciting development of advanced imaging infrastructure capacity that will allow a convergence of scientists from across the country to gain an unprecedented level of molecular insights into the complex systems and arrangement of cells in biologically relevant complex 3 dimensional environments.”

Participating Organisations include: Universities: University of Technology Sydney, RMIT University, University of Wollongong, University of Sydney, The University of Queensland, The University of New South Wales, Macquarie University, The University of Adelaide.

Institutes and Centres: Institute for Biomedical and Materials Devices, ARC Research Hub for Integrated Device for End-user Analysis at Low-levels, Institute for Molecular Horizons, the Heart Research Institute, ithree Institute, Centre for Translational Neuroscience, Australian Centre for Ecogenomics, ARC Centre of Excellence for Nanoscale BioPhotonics.

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Soft-glass imaging microstructured optical fiber

10 December 2018:

A proof-of-concept fabrication of a soft-glass imaging microstructured optical fiber has been demonstrated by CNBP scientists in a new research paper published in the journal Optics Express. Lead author of the paper is Dr Stephen C. Warren-Smith, CNBP Associate Investigator at the University of Adelaide who notes that it is envisaged that the glass-based optical fibers will find potential use in applications such as in-vivo white-light and spectroscopic imaging.

Journal: Optics Express.

Publication title: Soft-glass imaging microstructured optical fibers.

Authors: Stephen C. Warren-Smith, Alastair Dowler, and Heike Ebendorff-Heidepriem.

Abstract: We demonstrate the fabrication of multi-core (imaging) microstructured optical fiber via soft-glass preform extrusion through a 3D printed titanium die. The combination of extrusion through 3D printed dies and structured element (capillary) stacking allows for unprecedented control of the optical fiber geometry. We have exploited this to demonstrate a 100 pixel rectangular array imaging microstructured fiber. Due to the high refractive index of the glass used (n = 1.62), such a fiber can theoretically have a pixel pitch as small as 1.8 µm. This opens opportunities for ultra-small, high-resolution imaging fibers fabricated from diverse glass types.

Modulation of the nano-environment

15 November 2018:

A new CNBP research publication (lead author Dr Roman Kostecki, University of Adelaide) describes how molecular interactions can be modulated by defining the local nano-environment to give a specific chemical outcome.

Journal: ACS Applied Materials and Interfaces.

Publication title: Control of Molecular Recognition via Modulation of the Nanoenvironment.

Authors: Roman Kostecki, Sabrina Heng, Adrian M. Mak, Heike Ebendorff-Heidepriem, Tanya M. Monro, and Andrew D. Abell.

Abstract: Many biological processes are driven by the interaction of a host with a guest molecule. We show such interactions can be modulated by carefully defining the local molecular environment to give a specific chemical outcome. Particularly, the selectivity of a host toward two different ions (Ca2+ and Al3+) is defined by it being in solution or the physisorbed state. In solution, the host displays greater selectivity toward Ca2+. When physisorbed, the selectivity profile of the host is reversed with enhanced binding of Al3+. This demonstrates a single host molecule can be tailored to selectively bind multiple guests by altering its nanoenvironment.

A spiropyran-based nanocarrier

10 November 2018:

CNBP researchers have published a new science paper reporting on a new zinc responsive delivery system with real-time intracellular sensing capabilities. Lead author of the publication is Dr Sabrina Heng (pictured).

Journal: Chemistry.

Publication title: Spiropyran‐based Nanocarrier: A New Zn2+‐Responsive Delivery System with Real Time Intracellular Sensing Capabilities.

Authors: Sabrina Heng, Xiaozhou Zhang, Jinxin Pei, Alaknanda Adwal, Philipp Reineck, Brant Gibson, Mark Hutchinson, Andrew Abell.

Abstract: A new spiropyran‐based stimuli‐responsive delivery system is presented that encapsulates and then releases an extraneous compound in response to elevated levels of Zn2+, a critical factor in cell apoptosis. A C12‐alkyl substituent on the spiropyran promotes self‐assembly into a micelle‐like nanocarrier in aqueous media, with nanoprecipitation and encapsulation of added payload. Zn2+ binding occurs to an appended bis(2‐pyridylmethyl)amine group at biologically relevant micromolar concentration. This leads to switching of the spiropyran (SP) isomer to the strongly fluorescent ring opened merocyanine‐Zn2+ (MC‐Zn2+) complex, with associated expansion of the nanocarriers to release the encapsulated payload. Payload release is demonstrated in solution and in HEK293 cells by encapsulation of a blue fluorophore, 7‐hydroxycoumarin, and monitoring its release using fluorescence spectroscopy and microscopy. Furthermore, we demonstrate the use of the nanocarriers to deliver a caspase inhibitor, Azure B, into apoptotic cells in response to an elevated Zn2+ concentration. This then inhibits intracellular caspase activity, as evidenced by confocal microscopy and in real‐time by time‐lapsed microscopy. Finally, the nanocarriers are shown to release an encapsulated proteasome inhibitor (5) in Zn2+‐treated breast carcinoma cell line models. This then inhibits intracellular proteasome and induces cytotoxicity to the carcinoma cells.

Brain Foundation research gift awarded

30 October 2018:

CNBP Associate Investigators Dr Lyndsey Collins-Praino (University of Adelaide) and Dr Andrew Care (Macquarie University), together with CNBP Director Prof Mark Hutchinson have been awarded a highly competitive Research Gift by the Australian Brain Foundation.

The funds granted will help the team to develop a new technique that aims to prevent the spread of Parkinson’s Disease in the human brain.

Below: Dr Lyndsey Collins-Praino and Dr Care accept their Research Award (with Prof Hutchinson in absentia).

 

 

Best ECR presentation award

26 October 2018:

CNBP’s Dr Nisha Schwarz, has won ‘Best ECR Presentation’ at the South Australian Health and Medical Research Institute (SAHMRI) Research Showcase event, held Friday 26th October.

Nisha’s presentation was ‘Colchicine in CVD : An Ancient Therapeutic With Novel Applications. But How?’ During the talk she revealed some insights on its mechanisms specific to atherosclerosis.

Below – Nisha (middle) with other prize winners on the day.

‘Ingenuity’ promotes STEM study

23 October 2018:

‘Ingenuity’, a public facing event run by the Faculty of Engineering, Computer and Mathematical Sciences (University of Adelaide) was recently held at the Adelaide Convention Centre and CNBP science was represented!

The University event, showcasing final year student projects and achievements, was attended by thousands of school students, industry representatives and members of the general public, with the goal of encouraging and fostering an ongoing interest in STEM related subject areas (science, technology, engineering and maths).

This year saw CNBP PhD student Kathryn Palasis participate at the event, giving two presentations to approximately 300 school students on her research (the design and development of photoswitchable drugs) and describing her time at the University, with the aim of encouraging students to pursue a career in STEM.

“It was fantastic seeing the energy and interest in the room,” said Miss Palasis. “The feedback from staff and students was extremely positive and it was great to share my research and scientific passion with them all.”

“Hopefully we’ll see some of these young scientists studying at the University and then showcasing their own exciting areas of research in the years to come,” she said.

Below –  CNBP PhD student Kathryn Palasis delivers her talk.

 

3D printing of OCT probes

4 October 2018:

A new paper published in Scientific Reports demonstrates the feasibility of 3D printing of optical coherence tomography (OCT) fibre-optic probes. Lead author on the publication is CNBP’s Dr Jiawen Li (pictured).

Journal: Scientific Reports.

Publication title: Two-photon polymerisation 3D printed freeform micro-optics for optical coherence tomography fibre probes.

Authors: Jiawen Li, Peter Fejes, Dirk Lorenser, Bryden C. Quirk, Peter B. Noble, Rodney W. Kirk, Antony Orth, Fiona M. Wood, Brant C. Gibson, David D. Sampson & Robert A. McLaughlin.

Abstract: Miniaturised optical coherence tomography (OCT) fibre-optic probes have enabled high-resolution cross-sectional imaging deep within the body. However, existing OCT fibre-optic probe fabrication methods cannot generate miniaturised freeform optics, which limits our ability to fabricate probes with both complex optical function and dimensions comparable to the optical fibre diameter. Recently, major advances in two-photon direct laser writing have enabled 3D printing of arbitrary three-dimensional micro/nanostructures with a surface roughness acceptable for optical applications. Here, we demonstrate the feasibility of 3D printing of OCT probes. We evaluate the capability of this method based on a series of characterisation experiments. We report fabrication of a micro-optic containing an off-axis paraboloidal total internal reflecting surface, its integration as part of a common-path OCT probe, and demonstrate proof-of-principle imaging of biological samples.

Medical applications of light and fibre optics

20 September 2018:

A class of Year 11 Physics students from Loreto College, Marryatville, South Australia were visited by CNBP researcher Dr Jiawen Li, September 20th, 2018.

During the outreach visit Dr Li spoke on the medical uses of fibre optics technology and answered questions from the class, helping shed light on the life of a scientist and explaining the wide-range of career options open to STEM students.

“I really enjoyed visiting the school and found the session an extremely rewarding experience,” said Dr Li.

“Student questions following the presentation were well thought through and hopefully I helped in some small way to encourage the girls to continue their study of physics and other STEM related subjects.”

“Higher education potentially opens up a wide range of exciting career opportunities right across the science, engineering and medical disciplines,” said Dr Li. “And it would be great to see these enthusiastic students get to University.”

Feedback from the school post-event noted that the students had found Dr Li to be a fantastic role model and that her presentation session had been particularly inspiring.

Below: Students from Loreto College at the outreach session.

Peptides as bio-inspired electronic materials

7 September 2018:

A new paper with CNBP authors Jingxian Yu, John Horsley and Andrew Abell extends fundamental knowledge of charge transfer dynamics and kinetics in peptides and also open up new avenues to design and develop functional bio-inspired electronic devices, such as on/off switches and quantum interferometers, for practical applications in molecular electronics.

Journal: Accounts of Chemical Research.

Publication title: Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective.

Authors: Jingxian Yu, John R. Horsley, and Andrew D. Abell.

Abstract: Molecular electronics is at the forefront of interdisciplinary research, offering a significant extension of the capabilities of conventional silicon-based technology as well as providing a possible stand-alone alternative. Bio-inspired molecular electronics is a particularly intriguing paradigm, as charge transfer in proteins/peptides, for example, plays a critical role in the energy storage and conversion processes for all living organisms. However, the structure and conformation of even the simplest protein is extremely complex, and therefore, synthetic model peptides comprising well-defined geometry and predetermined functionality are ideal platforms to mimic nature for the elucidation of fundamental biological processes while also enhancing the design and development of single-peptide electronic components.

In this Account, we first present intramolecular electron transfer within two synthetic peptides, one with a well-defined helical conformation and the other with a random geometry, using electrochemical techniques and computational simulations. This study reveals two definitive electron transfer pathways (mechanisms), the natures of which are dependent on secondary structure. Following on from this, electron transfer within a series of well-defined helical peptides, constrained by either Huisgen cycloaddition, ring-closing metathesis, or a lactam bridge, was determined. The electrochemical results indicate that each constrained peptide, in contrast to a linear counterpart, exhibits a remarkable shift of the formal potential to the positive (>460 mV) and a significant reduction of the electron transfer rate constant (up to 15-fold), which represent two distinct electronic “on/off” states. High-level calculations demonstrate that the additional backbone rigidity provided by the side-bridge constraints leads to an increased reorganization energy barrier, which impedes the vibrational fluctuations necessary for efficient intramolecular electron transfer through the peptide backbone. Further calculations reveal a clear mechanistic transition from hopping to superexchange (tunneling) stemming from side-bridge gating. We then extended our research to fine-tuning of the electronic properties of peptides through both structural and chemical manipulation, to reveal an interplay between electron-rich side chains and backbone rigidity on electron transfer. Further to this, we explored the possibility that the side-bridge constraints present in our synthetic peptides provide an additional electronic transport pathway, which led to the discovery of two distinct forms of quantum interferometer. The effects of destructive quantum interference appear essentially through both the backbone and an alternative tunneling pathway provided by the side bridge in the constrained β-strand peptide, as evidenced by a correlation between electrochemical measurements and conductance simulations for both linear and constrained β-strand peptides. In contrast, an interplay between quantum interference effects and vibrational fluctuations is revealed in the linear and constrained 310-helical peptides.