Insights From Immunologists: Professor Jon Austyn

F4/80, clone CI:A3-1, is a well-characterized and extensively referenced macrophage and microglia marker. Recently, we had the honor of joining Professor Siamon Gordon, the father of F4/80, in celebrating its discovery over 40 years ago, alongside the past members of his lab who, in the decades since, have made significant contributions to macrophage research, and the scientific landscape as a whole.

We spoke to Professor Jon Austyn, Siamon’s first graduate student who carried out the original research identifying F4/80, about his remarkable scientific career. After becoming captivated by the complexity of immunology, Jon delved into the intricacies of dendritic cells, initially working as a postdoc in Nobel Laureate Ralph Steinman’s lab. After dedicating the subsequent decades to understanding the immune system, Jon has now co-founded a biotechnology company, iuvantium Ltd., which designs new vaccine formulations to improve the efficiency of the elicited immune response.

Bio-Rad (BR): When did you first become interested in a career in science?

Jon Austyn (JA): I always thought about an academic career, from my earliest years, as my aunt went to Girton College, Cambridge, to read medicine, and I always liked the concept that you could explore your own ideas. I also loved the humanities at school, but when it came to making a career decision, I thought I’d probably have a better option for a job in science.

So, I went to the University of Oxford to study biochemistry. It was a four year course and I really didn't enjoy the first three years. I was very frustrated because I was longing to get away from school and just taking notes, and when I arrived it was just like high school all over again. But then, thankfully, in the fourth year, there were two things that changed this.

The first was that we had to do a research project. I worked in the lab of a man called Don Wild, where they were studying a bacterial mutant that they didn’t know what the defect was. And so, I remember running these 2D gel electrophoresis experiments, and to my delight, the wild type versus the mutant had one spot missing, and I was able to identify it. They couldn't keep me out of the lab after that! So that’s why I did research.

The second thing that happened was that I chose to study immunology. I suddenly realized that this was the most incomprehensible and complex subject I’d ever encountered, and it was so frustrating and so mysterious I thought: “I need to understand the immune system.” And that’s really what focused my subsequent career. 

BR: How did you become interested in macrophages?

JA: Siamon Gordon had just arrived in Oxford from Rockefeller University in New York when I had finished my degree and Henry Harris, a professor of medicine at Oxford, recommended I speak to him about a PhD position in his lab. Kohler and Milstein had just described monoclonal antibodies and Siamon wanted to make monoclonal antibodies against the macrophage. So, I ended up with Siamon after that.

I wasn’t primarily interested in the macrophage. There were papers at the time suggesting that macrophages may be the accessory cell that you needed to get T cell activation and responses, and I was interested in that. When Siamon said to me, “It's probably not the macrophage. It's another cell called the dendritic cell” I thought, “Oh my goodness, I’m about to spend the next three years working on the wrong cell!”. But it was a way to get into immunology and it led me to the dendritic cell, which I focused a lot of my succeeding research on.

BR: Can you describe a highlight from your career?

JA: Well, of course, the discovery of F4/80! That was a big one.

I think other than that there are two moments of real discovery that come to mind. One was from one of my first graduate students, Chris Larson, who showed that dendritic cells migrate from heart transplants to the spleen, and this was the first evidence that the spleen was a potential source for rejection initiation. Up until then it was thought that it happened in the organs. And I’ll never forget that.

The second was when I collaborated with Dermot O’Hare, who was working on materials called layered double hydroxides, and we decided to look at whether they had any effect on the immune system. We found that these inorganic materials stimulated amazingly different types of immune responses. We assumed that their chemistry must somehow be involved in the type of immune response they were driving but we couldn’t make sense of it. So, we tried a systems vaccinology approach. We collected a massive amount of data and contacted a retired statistician who had a very complex statistical and multivariate analysis and asked him to analyze if there was any link between the data and the physical and chemical properties.

He told us that every single immune response correlates precisely with just three physiochemical properties. Remarkably, both human dendritic cell responses and mouse antibody responses conformed to this. So, if you use three different chemical properties, you can make accurate predictions about the immune response (William et al. 2014). That had never been done before.

BR: Can you tell us about your current research/role?

JA: Well, I tried to get funding to follow up on the physiochemical properties research but it never quite came through. During the pandemic, I spent a lot of sleepless nights thinking “if only we could have gotten the funding” because you could replace adjuvants in vaccines with these materials to induce different types of immunity and it could be a solution to COVID-19.

We contacted a large chemical company in Thailand (SCG) that funds the Center for Excellence in Chemistry at Oxford, and they agreed to fund a one year project. For that year, I was working very closely with a guy called Björn Schimmöller, who was head of R&D for SCG. After the year was over, we kept talking, and one day, he said to me, “Have you ever thought about starting a company?”. Long story short, he gave up his job, I gave up my retirement, and we co-founded iuvantium. Björn is now acting as chief executive officer (CEO) and I am acting as chief scientific officer (CSO).

I feel that after 40 years of trying to understand the immune system, I’m now ready to try and decode it! So, we’re developing these immune modulators to replace adjuvants to design vaccines, using our formula, based on the type of immunity needed for different types of disease. And then, potentially, we can go on and do something even bigger.

BR: What advice would you give to early career scientists?

JA: I think one of the biggest inspirations of my life came from my early months as a postdoc with Ralph Steinman. He identified the dendritic cell, but he could not get funding because there was a powerful lobby that believed it was just a macrophage. But he said to me, “I’m determined”. So, he persevered and amazingly, he eventually got the Nobel Prize in Physiology or Medicine for this discovery.

What I learned from that is if you believe in something, if you find something that gives you that sense of being able to create something worthwhile for the world, don’t be put off by the inevitable pushbacks. Don’t go into science unless you’re prepared to fight for what you think is most important but always treat it dispassionately. Always try and disprove a hypothesis.

Thank you, Professor Jon Austyn, for speaking with us about your impressive career and enlightening insights. We hope that our early career researchers are inspired by your passion for science!