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20 Nov 2020

Meet the team: Professor Sammy Bedoui unravels the complexities of the immune system

University of Melbourne Professor Sammy Bedoui, a laboratory head at the Doherty Institute.

Can you introduce yourself and your research?

My primary interest is in discovery research, investigating fundamental research questions about the immune system and how its cells decide to mount a response when faced with a particular challenge. This has major implications for human health. For example, whilst most people respond to SARS-CoV-2 with comparatively mild symptoms, some patients develop very severe disease and this is likely because their immune responses overshoot. The immune system fails to appropriately recognise the level of threat and mounts responses that are inappropriate. In some cases, this can kill the patient. The same can happen in the reverse, such as with HIV or some other viruses, where the immune system is fooled into believing that a more potent response is unnecessary, thus allowing the virus to persist. My research really asks that very simple question from a range of different angles: how does the immune system determine when to respond and when not to respond? While the question is simple, you can imagine that the answers are very complex.

You were recently awarded funding through the Australian Research Council (ARC) Discovery Project scheme for your research into cell death pathways. Congratulations, can you tell us more?

The question that we’re asking in this particular project is again very simple: why does the body have so many different ways of killing its own cells? At first thought, it sounds odd that the body would kill its own cells. We typically think of growth and the multiplying of cells when it comes to life. For instance, when an egg meets a sperm, this ultimately results in trillions of cells multiplying to create an organism.

“Cell death pathways are intriguing. Philosophers often say that life cannot exist without death and that death defines us. Even at the molecular level, this is true - without cell death there can be no regular life.”

Along the way, however, many cells also have to die. For example, the way our fingers develop is that the hand initially forms as a single bubble, but in order for fingers to arise, the cells that sit in-between our fingers need to die to prevent webbing between digits. It's a selective balance between which cells live and die, proliferate and don’t proliferate. There are many ways for cells to die and our research is now looking to understand why this is the case. What this may come down to is that we have multiple ways for cells to die as a fail-safe mechanism. This ensures that should one way of cell death be defective or unavailable; the organism can use a backup procedure to ensure that the cell in question can still be removed. While such research is very basic in its intent and purpose, the insights gained through this research will ultimately also highly be relevant for human health and also biotechnology.

You have a background in medicine. What brought you to the field of scientific research?

In Germany, I had a choice when completing school – either join the army or complete non-military civil service. I chose to do the latter and found myself working in a hospital by chance. Someone at the hospital said to me: “If you tell them that you want to study medicine, you will get a better job in the hospital.” So, I did that and they placed me in the operating theatre. My role there was focused on receiving patients, positioning them on the operating table and being an assistant- holding up a leg when it needed to be washed, that sort of thing. In between, I could watch the operations and many of the doctors were very happy to explain what they were doing and answering my millions of questions. This exposed me to medicine and completely fixed me up – I decided that I wanted to become a surgeon.

During my studies, I became more and more interested in how the body works rather than seeking to fix people with scalpels and thread. This coincided with another interesting choice. In Germany, if you study medicine and want to hold the academic degree of ‘Dr’ you need to complete a thesis. I took this as an opportunity to experience how medical knowledge was being generated and therefore joined a research laboratory, where I conducted experiments to investigate how the nervous system and the immune system communicate. I loved it and rather than graduating from Medicine after completion of my experiments, I accepted an offer to do more research in Japan and Australia for two years. By the time I returned to Germany to complete my intern year in surgery, medicine and neurology, it was clear that basic research was what I wanted to do. While I also thoroughly enjoyed clinical medicine and, in particular the interaction with patients, it came down to a simple equation for me. I felt that I could do two things well in life: I could have a life, do clinical medicine or do research. I had to let one go. So, I left clinical medicine behind and that’s how I ended up here.

As we meet the challenges of the COVID-19 pandemic, has this shifted the focus of your research in any way?

At the beginning of the year, we were beginning to investigate why only some cancer patients respond to immunotherapy and how this is related to the microbiome and metabolism of the patient. Essentially, we learned that you can't just look at the immune system, the microbiome or the metabolism in isolation but that it was important to disentangle the relative relationship between all these components in the one patient.  This is not trivial as each of these components is already enormously complex. This is further complicated by the fact only some patients respond to immunotherapy. So we also had to make sure that the relationship we observed between the immune system, the microbiome and the metabolism was also compared to whether patients responded or not.

Now this problem in cancer immunotherapy bears intriguing resemblances to COVID-19, where we still don’t fully understand why some patients control the virus without major symptoms while others become very sick or even die. Hence, we rapidly shifted our focus and are currently applying these approaches to COVID-19.

If somebody is looking to pursue your line of research, do you have any advice?

In general, I would always say the most important thing that you can bring to the table is curiosity. If it's curiosity that drives you, you will be able to make it. If you have true passion in your subject matter, then it's a wonderful job. For me, this is discovery and basic research. I believe that it's the beginning to the answer to every question in translation and clinical science.

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