Extraordinary vesicles

Professor Andrew Hill discusses the future of extracellular vesicles

By Dr Giselle Roberts

Extracellular vesicles (EVs), or cell particles, are transforming the way scientists think about disease and diagnostics. Once regarded as cellular trash, EVs may one day become a vehicle for the administration of therapeutics, or used as diagnostics for anything from pregnancy to cancer.

Director of LIMS, Professor Andrew Hill, is leading the scientific charge on EVs. He is President of the International Society for Extracellular Vesicles and Director of La Trobe University’s new Research Centre for Extracellular Vesicles. His lab is using EVs to develop potential diagnostics for brain diseases including Alzheimer’s, Parkinson’s and prion disease.

What’s in an EV?

GISELLE ROBERTS: Andy, you have devoted more than a decade of your career to understanding EVs. What do they do and why are they important?

ANDREW HILL: EVs play a fundamental role in a range of normal cellular processes, including cell-to-cell communication. After being released from the cell, these particles have the ability to travel to other cells, carrying proteins and genetic material with them. They also act as a trash dispenser, packaging up unwanted materials as part of an efficient rubbish removal process. And, they are involved in a number of pathological processes, including cancer.

GR: Scientists have been working on EVs since the late 1960s, but the field has really taken off in the last ten or fifteen years. Is that because of advances in technology, advances in scientific thinking, or both?

AH: A combination of the two. One of the challenges is that EVs are about 100 nanometres in diameter, and can only be seen by using an electron microscope. Even simple things like counting EVs took hours in the past. Luckily, technology has opened up new possibilities for scientists. Today, LIMS has a piece of equipment that counts EVs for us. Advances in other areas like proteomics and genomics has also enhanced our ability to look at thousands of molecules at a time. It has given us new perspective, and new avenues of research to pursue. This perfect storm between science and technology has transformed EV research from a niche area into a field that is attracting a lot of attention.

Research centre opens

GR: Tell me about the newly established Research Centre for Extracellular Vesicles.

AH: The Centre was launched in October 2017. We have a critical mass of EV researchers at La Trobe that is unparalleled in Australia. Over the past 18 months, our scientists  started meeting to discuss research and collaborations. Establishing a centre seemed like a natural extension of that. It is embedded within LIMS, but includes scientists from AgriBio and the School of Life Sciences.

GR: So what does the research portfolio look like?

AH: We all work on EVs, but in a variety of different settings. Professor Marilyn Anderson and Dr Mark Bleackley are working on fungi, Dr Maria Liaskos is researching bacterial vesicles that could be used as vaccines, Dr Ivan Poon is working to understand the role of EVs in cell death, and Dr David Greening is using them in reproductive biology. So we have a huge spectrum of research topics from plants, animals and humans, to bacteria and fungi. We all share a passion for EVs, but we also have our own distinct areas of research, which is great.

GR: What does the centre hope to achieve?

AH: I hope to see members collaborate on research projects, publications, grant applications and equipment bids. The centre is running a seminar series this year, along with a couple of symposia featuring international speakers. We also have several early career researchers, and I hope their involvement will be particularly beneficial for them. Collectively, it positions us well to be recognised as Australia’s leading institution in this area.

Industrial-strength EVs

GR: I am fascinated by the idea that scientists may one day use EVs as a drug delivery tool.

AH: Scientists have been able to achieve this in a lab setting, but the biggest challenge is trying to produce EVs in large quantities.

GR: And that’s where your collaboration with VivaZone Therapeutics Pty Ltd, SeerPharma and CSIRO comes in.

AH: Yes. Together we have received a $2.18 million Cooperative Research Centre Project Grant to develop a scalable manufacturing process that will allow us to produce large quantities of EVs for therapeutic purposes. Our contribution to the three year project involves isolating and characterising EVs and developing the scalable process. We are also being trained to adhere to Good Laboratory Practice, a set of principles intended to ensure the quality and integrity of the study.

GR: So after more than a decade working in the field, what do you still find exciting about EVs?

AH: They are complex. Cells that make EVs have the unique ability to decide what they want to send out, and that is what we are working to understand. There is so much we don’t know about the genetic material that has been repackaged. It’s fascinating to discover why, evolutionally, this mechanism has been preserved from various different organisms. And, we are making scientific headway. It is cutting edge, and so it’s very exciting.