I loved being a vet. I’ve always adored animals and working to help them was incredibly rewarding. But I kept being haunted by the cases that we couldn’t solve. I would do everything I was meant to do, and while some cases would turn out extraordinarily well, some just completely deteriorated. This was particularly relevant when it came to immune diseases.
I realised I wasn’t happy following the standards of treatment. I wanted to understand how to redefine those treatments, and improve them. It was a scary decision, but in my mid-20s I gave up my career and went back to study a PhD.
As I embarked on this change of career, I realised I didn’t just want to answer questions about animal immune systems. I wanted to do research that solves fundamental questions about how the immune system works, how we protect ourselves from infectious threats, why things go wrong, and I wanted that research to be relevant for all species, including humans.
I look at B cells – the cells that make antibodies that protect us from infectious threats.
B cells are an important cell type that we try to induce with vaccine responses. Each person has millions of different B cells. And each B cell is specific for one particular target – even though it has never seen this target. Our bodies have this amazing process of generating a huge diversity of B cells ready to protect you from threats you’ve never encountered, and threats that don’t even exist yet. It’s incredible.
When your immune system sees a threat for the first time, that one specific B cell finds its target, and then starts multiplying. If you are exposed to that same threat again, your body already knows how to counter it. This is the principle behind vaccination: you are teaching your immune system how to replicate very rare B cells that can immediately start making antibodies to protect you from a specific threat.
Our immune system is remarkably clever and elegant in its ability to combat infections that don’t even exist yet.
Unfortunately, some infectious threats are also very clever. Some try to hide from the immune system by making themselves look like our own proteins. This makes it difficult for the immune system to combat these threats without making antibodies that would also attack our own body. So how does our immune system protect us from these very challenging immune threats?
Our immune system is remarkably clever and elegant in its ability to combat infections that don’t even exist yet.
My research has found that the immune system of most people is still able to combat these incredibly challenging threats. Unfortunately, in some people, the immune system becomes confused. Instead of just making antibodies that attack the foreign threat, they make antibodies that also attack their own body, causing autoimmune diseases such as Guillain-Barré Syndrome. In people with this disease, the immune system gets confused when it is exposed to a normal threat, which could be anything, but in the majority of cases it is infection with stomach bugs like Campylobacter jejuni. Around 99.95% of people infected with this bacterium will have a stomach upset for a week or two, be uncomfortable, then totally recover. But for reasons we don’t understand, the immune system of people with Guillain-Barré Syndrome starts making antibodies which attack the body’s own nervous system instead of attacking the bacteria.
Guillain-Barré Syndrome can be a horrible, debilitating disease. Affected individuals present to hospital, initially struggling with weakness or tingling in their arms or legs, but then deteriorate quickly, which can lead to months in hospital – sometimes on a ventilator if the disease extends to the nerves that control breathing. At the moment we don’t understand why Guillain-Barré Syndrome patients make these nerve-attacking antibodies, and so there are no specific treatments that help address the cause of the disease.
Unfortunately, some infectious threats are also very clever.
My research group is at the Garvan Institute of Medical Research, located directly next to St Vincent’s Hospital in Sydney. This is a critical collaboration for us. Patients present to the hospital with early symptoms of Guillain-Barré Syndrome and as part of their normal diagnostic work, doctors take a small sample of their cerebral spinal fluid. Within an hour of it being taken – with the patient’s consent – my team at Garvan receives the sample and processes the cells within it for sequencing. We investigate the individual B cells, the antibodies they produce, and what they are targeting.
My team’s work is enabled by a major advance in medical research – the ability to analyse the genetic material of individual cells, which is known as single cell sequencing. We use this technology to look at individual B cells and understand which antibody each B cell is making and whether it binds the Campylobacter jejuni bacterium, human nerves or both. We are also exploring at a genetic level what caused these individual cells to go rogue and start attacking human nerves. Understanding what happens at a single cell level is helping us understand what drives Guillain-Barré Syndrome.
The other advance that has dramatically changed my research field is mRNA technology for vaccine design. This year’s Nobel Prize in Medicine was awarded to the two pioneering scientists who enabled the development of mRNA vaccines.
Making a new vaccine to target a specific threat used to take two to three years, just to get it to the point of testing. Now, thanks to mRNA technologies, we’re suddenly able to generate testable quantities of many different vaccine candidates at the same time in just a couple of months.
It’s my hope that these advancements will in future allow us to make safe and effective vaccines more quickly than ever before, so that we can prevent people from ever becoming infected with these challenging immune threats.
It’s such an exciting time to be an immunologist.
As told to Graem Sims
