Category Archives: MQ

New CNBP researcher at MQ University

6 October 2017:

CNBP welcomes its newest postdoctoral researcher to the team – Dr Jared Campbell who has just relocated to Sydney’s Macquarie University from the University of Adelaide.

The move will see Jared work closely with Centre Deputy Director Prof Ewa Goldys where he will be focused on using hyperspectral microscopy to research the effect of increasing age on the intracellular characteristics of mesenchymal stem cells – specifically their metabolic state as indicated by NAD+, as well as interventions which can ameliorate or reverse these effects.

Jared did his PhD at the University of Adelaide where he studied the interaction between metabolism and pluripotency in in vitro cultured embryos as well as the effect of improved metabolic control on the health of subsequently derived embryonic stem cells.

He then did a post-doc at the Joanna Briggs Institute where he applied systematic review and meta-analysis methodologies to investigate the impact of obesity on male fertility and the effect of AMPK activation on human health and lifespans.

Jared’s experience includes the investigation of intracellular signalling pathways, confocal microscopy, embryology, stem cell culture, epidemiology and meta-analysis.

He has also successfully supervised six masters and one PhD student to the completion of their projects.

A big welcome to ‘Team CNBP’ Jared!

New technique to aid bladder cancer diagnosis

25 September 2017:

A new and innovative automated computer technique has been developed by CNBP researchers that is able to significantly aid in the diagnosis of bladder cancer.

The technique—which allows suspect lesion images to be quickly and effectively analysed and then classified for cancer risk, has been reported in the medical journal ‘Urologic Oncology’.

“What we’ve done is develop a computer program to carry out an automated analysis of cystoscopy images,” says lead author of the research, Dr Martin Gosnell, Researcher at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) at Macquarie University and Director at Quantitative Pty Ltd.

Cystoscopy is one of the most reliable methods for diagnosing bladder cancer explains Dr Gosnell.

“Images are taken of the bladder and its insides for suspicious lesions during a routine clinical patient evaluation. Dependent on the findings, this initial scan can then be followed up by a referral to a more experienced urologist, and a biopsy of the suspicious tissue can be undertaken.”

The issue says Dr Gosnell is that the clinician examining the initial images makes a visual judgement based on their professional expertise as to the next steps of action that should be undertaken—such as the need to take a biopsy for subsequent pathological analysis.

“Potential errors and unnecessary further interventions may result from the subjective character of this initial visual assessment.”

“What we’ve done,” says Dr Gosnell, “is to create an automated image analysis technique which can identify tissue and lesions as either high-risk or minimal-risk.”

Read the full CNBP media release and the science paper here.

Journal: Urologic Oncology.

Publication title: Computer-assisted cystoscopy diagnosis of bladder cancer.

Authors: Martin E. Gosnell (pictured top), Dmitry M. Polikarpov, Ewa M. Goldys, Andrei V. Zvyagin and David A. Gillatt.

Abstract:

Objectives

One of the most reliable methods for diagnosing bladder cancer is cystoscopy. Depending on the findings, this may be followed by a referral to a more experienced urologist or a biopsy and histological analysis of suspicious lesion. In this work, we explore whether computer-assisted triage of cystoscopy findings can identify low-risk lesions and reduce the number of referrals or biopsies, associated complications, and costs, although reducing subjectivity of the procedure and indicating when the risk of a lesion being malignant is minimal.

Materials and methods

Cystoscopy images taken during routine clinical patient evaluation and supported by biopsy were interpreted by an expert clinician. They were further subjected to an automated image analysis developed to best capture cancer characteristics. The images were transformed and divided into segments, using a specialised color segmentation system. After the selection of a set of highly informative features, the segments were separated into 4 classes: healthy, veins, inflammation, and cancerous. The images were then classified as healthy and diseased, using a linear discriminant, the naïve Bayes, and the quadratic linear classifiers. Performance of the classifiers was measured by using receiver operation characteristic curves.

Results

The classification system developed here, with the quadratic classifier, yielded 50% false-positive rate and zero false-negative rate, which means, that no malignant lesions would be missed by this classifier.

Conclusions

Based on criteria used for assessment of cystoscopy images by medical specialists and features that human visual system is less sensitive to, we developed a computer program that carries out automated analysis of cystoscopy images. Our program could be used as a triage to identify patients who do not require referral or further testing.

Below: Dr Martin Gosnell and Prof Ewa Goldys.

Glycan identification and quantitation

21 September 2017:

Christopher Ashwood, CNBP PhD candidate, visited Ireland in September 2017, performing an oral presentation at the 16th Human Proteome Organisation World Congress with a presentation titled: “Open-glycomics: An open-access platform for software-assisted glycan identification and quantitation”.

He also visited the National Institute for Bioprocessing Research and Training (NIBRT) where he also presented his research.

Talk summary: Analysing glycomics data, the study of carbohydrates, is largely manual resulting in low throughput and can be subject to human error. Using a software package named Skyline, Chris has automated the most tedious parts of this data analysis and generated the data in a standard format for use by other glycomics researchers and bioinformaticians. Future research will standardise and automate this analysis further for application towards the currently booming biopharmaceutical industry.

CNBP science at the Calyx

12 September 2017:

CNBP researchers Dr Denitza Denkova and Dr Martin Ploschner took their luminescence and fluorescence science expertise to the general public, at a special after-hours event known as ‘Science at the Calyx’ at the Royal Botanic Garden in Sydney.

Presenting to an audience of approximately sixty people, the CNBP scientists focused on giving members of the public information about the origins of luminescence and examples of it being used – from everyday life to medical applications, and the amazing natural phenomenon of bioluminescence which can be found in plants, animals and fungi.

Following the hour long talk, there were demonstrations including the use of fluorescent bubbles, a ‘magical’ fluorescent screen, the showing of several fluorescent specimens and an examination of fluorescence in money and documents for security purposes. There was also as ample time for attendees to talk to the researchers about their work with fluorescent molecules and nanoparticles.

According to Dr Denkova, the event was highly rewarding.

“There was plenty of opportunity for personal interaction which was embraced by attendees. Many had an interest in the medical applications related to fluorescence, but there were also great questions on practical everyday activities – such as how to paint bikes with fluorescent paint to help improve road safety. Following the talk, people had the chance to walk around the beautiful garden with a UV torch in their hand to discover for themselves which plants are fluorescent. Both Martin and myself enjoyed communicating our science to a wider public!”

New technique to aid IVF embryo selection

28 August 2017:

Researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) have successfully developed an advanced new imaging technique, which can help assess the quality of early-stage embryos.

The research, reported in the journal ‘Human Reproduction’ has the potential to significantly benefit the IVF industry of the future, improving assisted reproduction outcomes for women.

“We use a special type of imaging to show differences in the metabolism and chemical make-up of embryos before they’ve been implanted,” says lead author Dr Mel Sutton-McDowall (pictured).

“This technique can give us an objective measure of which embryo to choose as part of the IVF process.”

This ‘hyperspectral imaging’ measures light that cells naturally produce during their normal activities. The light or ‘autoflorescence’ produced changes according to the chemical reactions or metabolism going on in the cell.

Being able to measure embryo metabolism is viewed by many researchers as one of the most important factors as to whether a particular IVF program will be successful.

However, says Dr Sutton-McDowall, fertility specialists take a largely subjective approach in deciding which embryos should be used.

“Pre-implantation screening of embryos generally takes place under a normal optical microscope. Although it’s quite easy to discern poor embryos (due to differences in uniformity), it is far harder for the clinician to determine objectively, the viability of the other embryos,” she says.

“The challenge is how to choose the single healthiest embryo out of this group to maximise the chances of pregnancy.”

Dr Sutton-McDowall sees the use of hyperspectral imaging as a new tool that can be combined with other diagnostic methods to provide a more accurate and objective embryo viability assessment.

“The benefit of hyperspectral imaging is that it can capture information-rich content of inspected objects. It analyses every pixel in an image for its light intensity at differing wavelengths,” she says

“This lets us drill down and analyse the hyperspectral signature of each individual embryo, looking for known or anomalous characteristics. It lets us discriminate between embryos, but also measuring metabolic differences within individual embryos. We predict that embryos that have cells with homogeneous (uniform) metabolic profiles are the healthier ones.”

To date, this imaging technology has only been tested on cattle embryos but Dr Sutton-McDowall notes that the technique is extremely promising.

“It offers benefits of being a non-invasive imaging approach that provides real-time information to the clinician,” she says.

The paper is accessible online.

Journal: Human Reproduction.

Publication title: Hyperspectral microscopy can detect metabolic heterogeneity within bovine post-compaction embryos incubated under two oxygen concentrations (7% versus 20%).

Authors: Melanie L. Sutton-McDowall, Martin Gosnell, Ayad G. Anwer, Melissa White, Malcolm Purdey, Andrew D. Abell, Ewa M. Goldys, Jeremy G. Thompson.

Abstract: 

STUDY QUESTION
Can we separate embryos cultured under either 7% or 20% oxygen atmospheres by measuring their metabolic heterogeneity?

SUMMARY ANSWER
Metabolic heterogeneity and changes in metabolic profiles in morula exposed to two different oxygen concentrations were not detectable using traditional fluorophore and two-channel autofluorescence but were detectable using hyperspectral microscopy.

WHAT IS KNOWN ALREADY
Increased genetic and morphological blastomere heterogeneity is associated with compromised developmental competence of embryos and currently forms the basis for embryo scoring within the clinic. However, there remains uncertainty over the accuracy of current techniques, such as PGS and time-lapse microscopy, to predict subsequent pregnancy establishment.

STUDY DESIGN, SIZE, DURATION
The impact of two oxygen concentrations (7% = optimal and 20% = stressed) during post-fertilisation embryo culture was assessed. Cattle embryos were exposed to the different oxygen concentrations for 8 days (D8; embryo developmental competence) or 5 days (D5; metabolism measurements). Between 3 and 4 experimental replicates were performed, with 40–50 embryos per replicate used for the developmental competency experiment, 10–20 embryos per replicate for the fluorophore and two-channel autofluorescence experiments and a total of 21–22 embryos used for the hyperspectral microscopy study.

PARTICIPANTS/MATERIALS, SETTING, METHODS
In-vitro produced (IVP) cattle embryos were utilised for this study. Post-fertilisation, embryos were exposed to 7% or 20% oxygen. To determine impact of oxygen concentrations on embryo viability, blastocyst development was assessed on D8. On D5, metabolic heterogeneity was assessed in morula (on-time) embryos using fluorophores probes (active mitochondria, hydrogen peroxide and reduced glutathione), two-channel autofluorescence (FAD and NAD(P)H) and 18-channel hyperspectral microscopy.

MAIN RESULTS AND THE ROLE OF CHANCE
Exposure to 20% oxygen following fertilisation significantly reduced total blastocyst, expanded and hatched blastocyst rates by 1.4-, 1.9- and 2.8-fold, respectively, compared to 7% oxygen (P < 0.05), demonstrating that atmospheric oxygen was a viable model for studying mild metabolic stress. The metabolic profiles of D5 embryos was determined and although metabolic heterogeneity was evident within the cleavage stage (i.e. arrested) embryos exposed to fluorophores, there were no detectable difference in fluorescence intensity and pattern localisation in morula exposed to the two different oxygen concentrations (P > 0.05). While there were no significant differences in two-channel autofluorescent profiles of morula exposed to 7% and 20% oxygen (main effect, P > 0.05), morula that subsequently progressed to the blastocyst stage had significantly higher levels of FAD and NAD(P)H fluorescence compared to arrested morula (P < 0.05), with no change in the redox ratio. Hyperspectral autofluorescence imaging (in 18-spectral channels) of the D5 morula revealed highly significant differences in four features of the metabolic profiles of morula exposed to the two different oxygen concentrations (P < 0.001). These four features were weighted and their linear combination revealed clear discrimination between the two treatment groups.

LIMITATIONS, REASONS FOR CAUTION
Metabolic profiles were assessed at a single time point (morula), and as such further investigation is required to determine if differences in hyperspectral signatures can be detected in pre-compaction embryos and oocytes, using both cattle and subsequently human models. Furthermore, embryo transfers should be performed to determine the relationship between metabolic profiles and pregnancy success.

WIDER IMPLICATIONS OF THE FINDINGS
Advanced autofluorescence imaging techniques, such as hyperspectral microscopy, may provide clinics with additional tools to improve the assessment of embryos prior to transfer.

CNBP at Macquarie Uni Open Day

19 August 2017:

‘The power of light to measure’ was the phrase commonly expressed by Centre researchers staffing the CNBP stand at this year’s Macquarie University Open Day.

This was in response to potential University students and their family members, who were looking to find out more about nanoscale biophotonics as well as to better understand potential opportunities that might be open to graduates who successfully gain a degree in biology, physics or chemistry.

Many of the visitors left the CNBP stand impressed as to the broad application of biophotonics in the healthcare, food safety and manufacturing sectors. They also learnt more about the current activities of the CNBP, particularly in creating new sensing and imaging technologies to better understand molecular activity taking place within the living body.

The Open Day at Macquarie University saw many thousands of people visit Campus and engage with both staff and current students, in their exploration of courses open for undergraduate study.

Below, CNBP researchers Dr Wei Deng (left) and Dr Lianmei Jiang (right) get ready to talk nanoscale biophotonics as the doors open at the 2017 MQ Uni Open Day.

 

Welcome to a new CNBP researcher

27 July 2017:

CNBP welcomes its newest researcher to the team, Shi Xian (Edward) Moh who is based at Macquarie University.

Edward has previously been a part of Prof Nicki Packer’s glycomics group, successfully undertaking both his Honours and PhD study under her supervision. His study included detailed analysis of glycans, glycopeptides and glycoproteins and more specifically, research into using the glycosylation on the antibody immunoglobulin M (IgM) for specific labelling.

At CNBP, Edward will be initially examining functionalisation of the IgM antibody and other proteins, via chemo-enzymatic engineering of the glycans, for reproducible, multi-purpose labelling suitable for targeting specific cellular molecular receptors.

Edward’s experience includes detailed characterisation of proteins and their glycosylation by mass spectrometry; molecular biology of protein expression and purification, synthetic biology techniques, separation technologies; and coaching and advising undergraduate students in the world’s largest international synthetic biology competition, iGEM.

Welcome to the CNBP team Edward!

 

Nanotechnology meets bioengineering

29 June 2017:

The Fudan-UH-MQ Workshop on ‘Nanotechnology meets Bioengineering’ was well supported by CNBP researchers at Macquarie University,  Wed 28th June – Thu 29th June.

A joint workshop, organised within the framework of University wide trilateral collaboration between Fudan, Hamburg and Macquarie, the event aimed to enhance collaborations between all three universities as well as generate potential cotutelle PhD candidates.

CNBP researchers presenting at the workshop included:

Prof. Nicolle H. Packer (CNBP Chief Investigator, pictured)
Cellular glycosylation: opportunities for discovering new molecular targets.

A/Prof. Anwar Sunna (CNBP Associate Investigator)
A platform technology for the self assembly of functional materials.

A/Prof. Guozhen Liu (CNBP Associate Investigator)
Nanotools for in vivo cytokine monitoring in neuroscience.

Dr. Nicole Cordina (CNBP Research Fellow)
Functionalisation of fluorescent nanodiamonds for bio-imaging applications.

Below: Prof. Nicolle Packer presents her talk on glycans.

New PhD candidate Fuyuan Zhang

27 June 2017:

CNBP welcomes its latest PhD candidate Fuyuan Zhang who will study under the supervision of Center ARC Future Fellow A/Prof. Guozhen Liu at Macquarie University.

Fuyuan’s project is to develop assays to detect plant microRNA, diagnostic markers for response to pathogen or virus infection in plants, and subsequently to integrate these assays to an in vivo device for plant disease early diagnosis.

Funded by the Cotutelle PhD program between Macquarie University and Tianjin University of Science and Technology (TUST), China, Fuyuan has expertise in the design of assays for detection of toxins in food samples; the preparation of fluorescent nanomaterials; and the development of computer simulations and modelling .

Welcome to the CNBP team Fuyuan!

Neurophotonics Summer School

21 June 2017:

This years Neurophotonics Summer School held in Quebec, Canada, June 11-21, was attended by three CNBP members – Vicky Staikopoulos (University of Adelaide, pictured), Antony Orth (RMIT University) and Varun Sreenivasan (UNSW).

The school focuses on teaching physics and biology and how they can merge, and runs for 10 days and includes 14 lectures from world class speakers and 10 workshops that teach the latest technology in the bio-imaging of the central nervous system.

For the last 4 days of the summer school, students are given a project to participate in for direct hands-on experience which is then presented on the last day,  with prizes awarded for the top 3 presentations.

This year, equal second prize was given to Vicky Staikopoulos for her work on Digital Holographic Microscopy in red blood cells.