1 Dec 2017

Never a better time for immunology, says Department head

Professor David Tarlinton describes the Immunology department's
research. Video 2:07 min
by Anne Crawford

Professor David Tarlinton, one of Australia's foremost B-cell immunologists, reflects on his time in the field, his role heading Monash University’s Department of Immunology and Pathology, and tells of his own laboratory’s work. He points to two exciting new laboratories that will soon join the Department’s existing groups. 

When I was an undergraduate I did my honours in bacterial genetics, never intending to be an immunologist. I did a rotation in an immunology lab at the start of my PhD at Stanford University in California, and fell in love with it. I like the multiple levels and complexities of the field. Balanced with that, however, is the simplicity of immunology – it has a particular purpose and it is so perfectly evolved to achieve that purpose. Having said that, most of the work we do revolves around circumstances where the immune system is not working – where it’s inappropriately activated, for example in auto-immune or inflammatory diseases, when it doesn’t work in the case of immune deficiency or is uncontrolled in various forms of cancer.

How has the field changed over the years?

When I started my postdoctoral work with Gus Nossal in 1991 most immunology was cellular – how cells behave and interact with each other. The field has expanded in two directions – it has gone down to the point of individual molecules in individual cells to determine how the change in expression of a gene or location of a protein in a given cell at a given time alters its behaviour. At the same time, the scale has increased, looking at and modelling the behaviour of cell populations, creating mathematical formulae that will predict outcomes in ever-more refined ways at larger organisational levels and intersections of different cell types, not only other immune cells but also other cells and organs of the body.

Now we have a much better understanding that the immune system is connected to many other components of the body. For example, the association between the neurological system and the immune system – they clearly intersect with each other, not only in that some neurological diseases are auto-immune diseases but also in that one’s psychiatric state can influence how well one’s immune system functions and vice versa. It’s always been suspected that this was true but now there are molecular determinants of that.

Several technological revolutions underlie the advances in both of these directions – it’s just been extraordinary in pace and scale. What’s really amazing to me, and may seem paradoxical, is that a lot of therapeutics that we in the field are working on are based on technology that arose in the ‘70s for making monoclonal antibodies – a very simple process yet incredibly powerful technology more or less unchanged at its core.

Another change that’s occurred over the years is that science has become much more commodified than it was. When I was younger we made everything we used, more or less. Now, because of the scale of science and its global nature, there are companies that can make a good living out of providing what previously were boutique pieces of equipment and reagents.

Current papers now are quite complex and multifaceted, not just with laboratory skills, but with multiple groups usually contributing to them. We need to collaborate with other groups that are skilled in areas outside our capabilities, such as proteomics, bioinformatics and imaging. This provides enormous power and depth to our research efforts and accelerates our progress way beyond that which we could achieve alone. Australian science and immunology in particular, has been outstanding in its collaborative approach.

Basically, there couldn’t be a better time to be doing immunological research.

You took over the reins of the Department in January 2016 after 26 years as a basic scientist at the Walter and Eliza Hall Institute – what has that change involved?

The opportunity to shape a department and position it for the next 10 to 15 years was a fantastic one, an opportunity to contribute to the continuing development of immunology as a discipline in Australia. It’s been a very steep learning curve on many fronts; with the university and school structure, the intersection with the hospital, managing – if that’s the right word – the laboratories and personnel in the department. My main contribution will be in shaping the department’s future by recruiting new groups into it.

Another role is to better integrate our researchers into our clinical environment. We’re in a perfect position to take advantage of patient cohorts because we’re located adjacent to the Alfred – that’s something that distinguishes us from many of our peers and competitors. The role is a fundamental change from what I was doing previously, which was very basic work. It’s fantastic to see that all of our labs in some way have or are developing some clinical intersection. As a small example, my own group interacts with a lung transplant group at The Alfred to look at the issue of graft rejection mediated by antibodies. Our speciality is in the production of antibodies, particularly in response to immune challenges – and a graft is a massive challenge to your immune system! What we’re interested in is defining the role antibodies play in graft rejection.

What other research is your Immune Memory Laboratory conducting?

The work of my own laboratory focusses largely on the basic understanding of B lymphocyte behaviour. Our narrow interest is in antibody secreting cells, how they are produced and survive. This feeds into a huge number of clinical conditions, pretty much any disease in which the pathology is due to antibody production. We are doing preclinical research with lupus, an auto-immune disease, looking at targeting antibody secreting cells in a way that would reduce antibody production in patients and reduce the pathology.

We are also interested in how immunological memory is generated and how it’s maintained. Immunological memory can be thought of as a parallel of neurological memory; your immune system is designed so that when you successfully deal with an infection, you retain a memory of that encounter so that when you are exposed to that infectious agent for a second time you respond to it much more rapidly. If the system worked perfectly you would only ever experience one set of symptoms with any infection as your system would deal with subsequent exposure before the bacteria or virus was able to cause any serious pathology or clinical symptoms. The real challenge with immunological memory is how to develop it in a way that it not only remembers this year’s flu but can pre-empt the one you may get next year with its slight variations. I’ve worked for many years in cellular dynamics through which memory is established and still find it fascinating.

Have there been any highlights so far?

Our recent study into the role played by an enzyme called PRMT1 in clearing infection was a research highlight for us – though it was a highlight that took a long time!

We have another coming to fruition in the next few months, which will be on the topic of how we generate memory.

Are there any other developments for the Department on the horizon?
 
Two new groups will start early next year. New Zealanders Ben Marsland and Nicola Harris, who have been working in Switzerland, are coming to set up labs. Ben is a microbiome expert particularly interested in the lungs. Nicola is interested in parasite behaviour, in intestinal worms for example, and how the presence of those parasites, which are endemic in some parts of the world, influences the immune system in its response to everything else. The effect they have is to influence the immune system’s response to both self and foreign antigens, so in some of those countries where parasites exist, there are much lower levels of auto-immune diseases than we have. Hopefully, through Nicola’s work, we can harness the beneficial aspects of parasite infection without the dangers and pathology of the infection itself to improve health and better treat immunological diseases.

Read here about the other laboratories in Monash University's Department of Immunology and Pathology.

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