Monthly Archives: October 2019

CNBP conference veteran talks about his links to the Centre

Professor Dennis Matthews is one of CNBP’s oldest friends, having been coming to Australia from his home in California each year for nearly seven years as a member of its International Science Committee.

“I’ve actually been coming here since before the CNBP inception. They were just getting their act together for the initial grant when I first visited,” he says.

Professor Matthews was trained as physicist, but for most of his working life he has been involved in the development of medical devices.

His multidisciplinary life is reflected in his position as professor at University of California Davis in both the Department of Neurological Surgery and the College of Engineering. He was at one time also director of UC Davis’ Center for Biophotonics, Science, and Technology.

“I was hired into the neurological department not because I knew anything about neurosurgery but because they wanted their physicians to have more opportunity to do early stage research, even before it could be translated to the clinic,” he says.

He “abandoned physics 30 or 40 years ago”, drawn to things that were more hands-on and, around that time, he met a medical doctor who wanted to develop better instrumentation.
“I told him I didn’t know anything about medicine so he should go away. But he didn’t.”

That started a long history of working with doctors and bioscientists to develop technology that helped in their work.

“Biological scientists are incredibly smart at what they do but they are not so smart at measuring it,” he says.

“I don’t know what their problems are, of course, so they tell me what they are trying to achieve and I tell them ways to get at the solutions to their problems – and we help each other along the way.

“What I like about it, and CNBP works very nicely in this respect, is that you ‘bootstrap’ it. I tell the bioscientists I can do something but I’m not quite sure I know how to do it. So they challenge me to make technology progress at the same time.”

He believes CNBP has some unique strengths – “I wouldn’t travel around 13,000km to come here otherwise”.

Dennis Matthews presenting at CNBP’s 2019 conference

He was first introduced to the centre by the inaugural director, Professor Tanya Munro. “I thought she had an extremely good vision of where all this could go and perhaps an even better way of communicating that vision.” Since then, he says, current director Professor Mark Hutchinson has emerged as an incredible thought leader as well.

Professor Matthews says he likes the way the CNBP brings themes together and its “Mission Impossible” approach to throwing multidisciplinary teams of experts at problems.

As a technologist he was also drawn to the IPAS fibre optics group, and the way it was developing fibre sensors to interrogate places that might otherwise be invisible.
Two biological research themes particularly interested him.

“Many of the things here are important to me but there were two that were exceptional and that was Mark’s [Hutchinson] work on neuroscience applied to pain, and particularly his interest in developing a “painometer”.

He was also attracted to the IVF research under Chief Investigator Professor Jeremy Thompson.

“My daughter had two children by IVF and so my interests were already a bit piqued. But I was also interested to see if we could make the whole thing work better.”

Secondly was the possibility of making sure the highest quality embryos were developed and then implanted.

“That whole notion was extremely fascinating and provocative to me,” he says. “I think that we are going to learn how to make embryos healthier in normal conception. And if we can make the healthiest baby possible it can lead to a lifetime of good health.”

Personal experience also lay at the heart of his interest in Professor Hutchinson’s work on pain, which, while important to help people cope at a personal level, he sees as a potential solution to the opiate crisis.

“At the moment we are only delivering pain-masking drugs,” he says. “These powerful drugs don’t do anything except make people not care if they hurt – they still hurt.”

He is helping with the task of looking for biomarkers that might underpin such a measuring device.

“I think it’s possible, but I don’t know yet what the right measurements are,” Professor Matthews says. “And the problem with humans is there is no single recipe, so if we do get a panel of biomarkers that said my pain level was 6 it could be completely wrong for you.

“So we need some way to normalise it so we can say this is a baseline for an individual.”
Professor Matthews is particularly drawn to the CNBP’s focus on envisioning the ultimate translation of the technology.

“So instead of just filling the journals with more manuscripts it is also important in biosciences that you keep in mind that your work will, in the end, actually affect patients.

“The question we should always be asking is ‘how do we get doctors to have the latest technologies to work with?’.”

Cell surface sensors could advance precision medicine

1 October 2019:

Researchers have found a way to identify multiple cell signalling proteins using a single cell rather than the billions of cells used previously.

The new measurement technology, developed by researchers at the ARC Centre of Excellence for Nanoscale Biophotonics, brings precision medicine a step closer.

“Cells secrete various messenger molecules, such as cytokines. They may indicate the presence of a disease or act as a driver of key therapeutic effects,” says Dr Guozhen Liu, lead author of paper detailing the technology.

The method, termed OnCELISA, uses antibodies attached on specially engineered cell surfaces to capture cytokine molecules before they have a chance to disperse away from the cell.

The secreted messenger proteins such as cytokines are reported, at the single cell level, by using fluorescent magnetic nanoparticles.

Cytokines secreted from cells play a critical role in controlling many physiological functions, including immunity, inflammation, response to cancer, and tissue repair.

 

The image represents our sensor during the process of detecting cytokine molecules being secreted from cells. The sensor is represented by a pair of Y-shaped antibodies, the capture antibody (purple stem) and the detection antibody (pink stem).

The OnCELISA system can be used for ultrasensitive monitoring of cytokine release by individual cells, and it can also help discover cell populations with therapeutic value.

“The ability to identify and select cell populations based on their cytokine release is particularly valuable in commercial cell technologies and it can help develop unique products, such as future non-opioid pain relief” says Dr Liu.

“Importantly, our design uses commercially available reagents only, so it can be easily reproduced by others,” she adds.

While the published work focuses on specific proinflammatory cytokines IL-6 and IL-1β, the method is potentially suitable for a broad range of other secreted proteins and cell types.

The new technique represents an advance on traditional methods such as the enzyme-linked immunosorbent assays (ELISA) that detect average levels of secreted molecules from cell ensembles.

The OnCELISA takes the ELISA approach to its absolute extreme, by detecting cytokines on the surface of individual, single live cells.

The publication has been reported by prestigious iScience journal and can be found at https://www.sciencedirect.com/science/article/pii/S2589004219303578.

Journal: iScience

Publication Title: A Nanoparticle-Based Affinity Sensor that Identifies and Selects Highly Cytokine-Secreting Cells

Authors: Guozhen Liu; Christina Bursill; Siân P.Cartland; Ayad G.Anwer; Lindsay M.Parker; Kaixin Zhang; Shilun Feng; Meng He; David W.Inglis; Mary M.Kavurma; Mark R.Hutchinson; Ewa M.Goldys

Summary: We developed a universal method termed OnCELISA to detect cytokine secretion from individual cells by applying a capture technology on the cell membrane. OnCELISA uses fluorescent magnetic nanoparticles as assay reporters that enable detection on a single-cell level in microscopy and flow cytometry and fluorimetry in cell ensembles. This system is flexible and can be modified to detect different cytokines from a broad range of cytokine-secreting cells. Using OnCELISA we have been able to select and sort highly cytokine-secreting cells and identify cytokine-secreting expression profiles of different cell populations in vitro and ex vivo. We show that this system can be used for ultrasensitive monitoring of cytokines in the complex biological environment of atherosclerosis that contains multiple cell types. The ability to identify and select cell populations based on their cytokine expression characteristics is valuable in a host of applications that require the monitoring of disease progression.

Link: https://doi.org/10.1016/j.isci.2019.09.019