Dr Sabine Piller, medical research scientist

Medical research scientist

Dr Sabine PillerSabine Piller was born in 1970 in Vienna, Austria. In 1991 she completed a degree at the University of Vienna, majoring in zoology, botany, chemistry and physics. She moved to the USA for further studies and in 1993 received an MSc from the University of Alabama at Birmingham (UAB) where she researched the gill physiology of marine crabs. From 1993-94 Piller worked in the Department of Neurobiology at the University of Vienna.

Piller continued her studies of ion channels at the Australian National University, working on a protein of HIV named Vpr. Her PhD research, completed in 1998, was important in that it was the first time any HIV protein had been shown to function as an ion channel. From 1998-2000 Piller returned to UAB as a postdoctoral fellow in the Center for AIDS Research. Piller returned to Australia in 2000 when she was awarded a Young Investigator Award from the Centre for Immunology (CFI), the research campus of St Vincent's Hospital, Sydney. As a senior research officer/group head she is working on several projects involving Vpr and gp41. In addition to her work at CFI she is simultaneously adjunct lecturer in the Department of Medicine of the University of New South Wales and visiting fellow in the Division of Biochemistry and Molecular Biology at the John Curtin School of Medical Research (JCSMR).

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Interviewed by Ms Marian Heard in 2001.

Contents


An early fascination with marine biology

Sabine, where were you born?

I was born in Vienna, Austria, on 8 January 1970, as the oldest daughter in a blue-collar family – my Dad is an airplane engineer, and my Mum was a secretary and then stayed home after my sister was born.

What early experiences influenced your decision to go into science?

Probably one of the most exciting experiences was when I was two years old and my parents took me to the Mediterranean. For the first time I had a snorkelling mask on my face and got to see the underwater world, which from then on was a real fascination.

I remember that at the age of six, in my first year of primary school, we had to write an essay on what we would like to be when we were older. I wrote that I wanted to become a ‘deep-sea diver’, and although that later changed to ‘marine biologist’, it basically was the same thing. And my parents fostered that interest in marine biology, taking us on holidays to the Mediterranean almost every summer so I could go snorkelling and continue my passion for the underwater world.

I learnt scuba diving at the age of 14. (Normally the German federation of scuba divers only allows you to start scuba diving at 16, so to start early I had a special permit.) That was also a very important experience in my life. My mother was very worried about me; my father thought if I went in and did this first dive I would never ever do it again. But I came out totally fascinated. Diving and marine research were what I wanted to do for the rest of my life.

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Transatlantic differences in universities

After finishing high school, you went on to study science at the University of Vienna. What were your subjects there?

In the Austrian university system, for an undergraduate degree you have to get a really good background. In the first part of your studies you can’t choose your subjects, so I covered the whole lot: chemistry, physics, general biology – botany, zoology, genetics, microbiology, the whole biology field. You have to take all these classes. But I do have quite a strong physics and chemistry background because in high school I specialised in physics and chemistry, and probably also because my Dad is an engineer.

While you were studying at university, you made a trip to the United States to visit a friend. That became a turning-point for you, didn’t it?

Absolutely. It came about because I needed one more lab to finish up the first part of my studies, and basically the students who had been studying the longest time got selected first. Having to wait a whole year to get into that lab was a really bad experience, because I was on track with my studies and it felt like the lazy students got favoured.

In the United States, visiting my friend, I sat in on a two-hour class, late in the evening. Everybody was tired, so the instructor told us to have a break and then we convened back after 15 minutes. I thought, ‘Oh well, it will still finish at the full hour, so we only have 45 minutes left now.’ But he continued for an extra 15 minutes. He just said, ‘You paid for a full two hours, and you should get your money’s worth.’ The whole attitude of teachers there, the student-teacher relationship, was quite different from what I was used to in Austria. Students were openly asking questions and were encouraged to ask them, whereas in Austria you were usually told, ‘Well, you’re supposed to know this.’ It was a really great experience for me, and I decided that I wanted to go overseas and study in America because I didn’t like the Austrian system any longer.

So when I came home I applied to the Austrian Ministry of Science and Research, and got a six-month scholarship to study in America. I was then further funded to continue my Master of Science research at the University of Alabama at Birmingham.

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A marine biology project leads to proteins as ion channels

What work did you do for your Masters degree at the University of Alabama?

I wanted to get into marine biology, so I worked in the Biology Department with Professor David Kraus and his wife Jeannette Doeller on two very closely related marine crab species, Callinectes sapidus and Callinectes similis. (They are like your blue swimmer crabs here – which you actually get to eat, as well.)

These crabs live in an estuarine environment, where the fresh water from rivers comes into the ocean and meets the salt water, so they experience regular changes in the salinity of the water. Every time it rains and more fresh water comes in, the salt concentration changes. The two species have the same preying behaviour, what they eat. So why can one of the species survive in fluctuating salt concentrations, while the other one is much more restricted, needing a certain salt concentration and unable to survive in fluctuating salinities? That was my topic.

I found differences in the gill tissues with which the crab species breathe. Towards the end of my project it turned out that these tissues, which also regulate the salt concentration in the crabs’ body fluids, differed in the proteins that can form ion channels – basically a protein that goes across a membrane and can shuttle ions, charged particles, across. That lab was not set up to study ion channels, but after the end of this project I wanted to go on and learn, somewhere, more about those specialist proteins that form ion channels.

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The PhD project: moving to ion channels in viruses

After you completed your Masters, you returned to Austria for a year to earn some money. Then you applied to do your PhD in a number of places around the world. You turned down an opportunity to work in Alaska, in favour of taking up a PhD scholarship at the Australian National University.

I had the offer of an Overseas Postgraduate Research Scholarship, but before deciding on it I came and visited the John Curtin School of Medical Research at the ANU to meet with my prospective supervisors, Professor Peter Gage and Professor Graeme Cox, basically just for a chat. I had originally applied for the scholarship because I knew they were doing ion channel research. But before coming around the world to do my PhD here, I wanted to know what they were working on and if I wanted to do that type of research. I was very fascinated by Professor Graeme Cox. His enthusiasm as a researcher really captured me and he was probably the reason why I decided to take up the project.

Professor Peter Gage is a neuroscientist whose group works on studying ion channels in the human brain. They’re made out of several sub-units and are very complicated to study. He is trying to work out exactly how the ions move across a membrane barrier through those channels. At the time that I joined, he had just started to look at proteins from viruses that also can form ion channels. They are much smaller proteins and the idea was, ‘If we can understand how the ion channels work in viruses, in a much simpler system, maybe that will give us a clue to how they work in the brain.’ So he had a student studying an ion channel from the influenza virus.

Graeme Cox is basically the biochemist of the team. He was going through several other viral proteins from all kinds of different viruses, deciding from similarities in their structure whether any could possibly also form ion channels. Out of the proteins on the list, I picked the virus protein Vpr, from HIV virus – I thought, ‘Well, if I work on viruses, HIV sounds really exciting.’ And having decided on that first trip out here what I wanted to work with, I then came back a couple of months later to take up my scholarship and start working on that project.

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Linking ion channels to AIDS dementia: an exciting hypothesis

Why was your PhD work important?

It was very important because we showed that that particular protein of the HIV virus, Vpr, does form an ion channel – the first time any HIV protein has been shown to function like that. We went on to identify which part of the protein forms the ion channel, and then, because this ion channel’s characteristics were quite different from those of the ion channel in the influenza virus, we speculated that this one might be involved in the AIDS dementia of HIV patients. Many HIV patients in their late stages become demented and have problems with motor control and cognitive problems but it is so far not understood how this disease comes about and why it affects some patients and not others.

Since I have shown that this viral protein from HIV forms an ion channel, we have used neurons, brain cells, from rats to show that if this protein is present on the outside of neurons it can actually form an ion channel in the membrane of the neurons, and completely abrogates the normal functioning of the brain cells by interrupting the ion gradients across there. That is very exciting: if we can prove that that is taking place in the patients, perhaps drugs can be developed to alleviate the horrible AIDS dementia problems that they face.

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Learning to study fully infectious HIV safely

What did you do after your PhD?

I returned to the US, to a different department of the University of Alabama at Birmingham. I worked in the lab of Eric Hunter, the director of the Center for AIDS Research. I basically went there because by the end of my PhD thesis work I was quite fascinated by how the HIV virus works but I had only worked with one part of that virus, one protein, and I had never come into contact with the entire virus. And to learn more about the entire virus I needed to learn how to work with a fully infectious virus. So part of my postdoc project in the US was to learn all the techniques that I needed for that. I learned how to work with all the proteins together in the live virus, under special physical containment facilities at what is called the PC3 level.

While I was there I studied a different protein of the HIV virus, a glycoprotein called gp41. It is on the outside of the virus, and it is very important in making the virus infectious. If the protein isn’t there or is truncated, the virus is non-infectious. And so it is interesting to study. Also, that particular protein has a very unusual long part on one end of it, and we made mutations in the protein by changing certain of its building blocks, to see what effect those changes would have.

People are quite concerned about the chance of contracting AIDS. Did you think about the risks of working with the fully infectious virus?

HIV is quite a safe virus to work with in a laboratory setting. The virus has a lipid bilayer around it. Normal bleach and detergents can actually remove that lipid bilayer and the virus is then non-infectious. Also, the whole training that goes with certification to work with the infectious virus is very strict. You work under very safe conditions. I feel that it’s much safer to work with it in a laboratory setting, where you know the risks and what you are working with, than it is in a hospital setting, where you work with patients’ blood samples that may contain all kinds of much more infectious viruses like hepatitis B and hepatitis C. So I believe that knowing the risk and actually controlling for it, and working under very safe conditions in those facilities, is quite safe – otherwise I really wouldn’t have done it!

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Is Vpr really linked to AIDS dementia? Testing the hypothesis

What brought you back to Australia after your postdoc, and what are you currently working on?

Well, my husband is Australian and he really wanted to come back. (He absolutely didn’t like it in the US.) The other reason is that I was awarded a Young Investigator Award from the Centre for Immunology on the research campus of St Vincent’s Hospital, in Sydney.

At the moment I have three main projects running, two of them still on the virus protein Vpr that I worked on in my PhD, and one on the protein that I worked on through my postdoc. We are just starting to write up publications from these very exciting projects.

For one of the Vpr projects we have a collaboration with Dr Bruce Brew, who is a neurologist. He has stored away about 4000 samples from patients who have developed AIDS dementia, and now I’m in a unique position to answer the question that came up during my PhD: whether the viral protein Vpr is actually causing AIDS dementia, or has anything to do with that part of the disease. We are trying to set up an assay to find out if the viral protein Vpr is present in the brain fluids, because that has so far not been shown at all. Vpr is known to be normally present inside the virus; it is packaged into the virus. However, for Vpr to form an ion channel into neuronal cells (as I showed in my PhD research), it needs to be present outside of the virus, in the blood and/or the brain fluids.

We are trying not only to find out if Vpr is present in the brain fluids but also to quantitate how much of it is present, and then to correlate that to the disease stage. Is it possible that patients who develop AIDS dementia have more Vpr in their brain fluids than patients that do not develop the disease? That’s very exciting, and we are hoping to get funding for this. We basically have the assay developed and hopefully by next year we should be able to screen Professor Brew’s 4000 patient samples. He has just got a grant from the National Institutes of Health (NIH) – the US funding agency equivalent to the National Health and Medical Research Council here – so that we will be able to receive additional patient samples from all over the world, and to come up in the next couple of years with a very sound statistical analysis to check for a link of that protein to AIDS dementia.

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How does HIV become resistant to drug treatments?

The second Vpr project includes collaboration with another MD, Professor David Cooper, and his group. They have identified HIV patients who are resistant to the current drug treatment, called Highly Active Anti-Retroviral Therapy. Two enzymes in the virus are blocked by the drugs, but mutations, changes, in those enzymes are causing the virus to be able to emerge and be resistant to the drugs. For a long time now, physicians have been ordering a screen of the genes to see if those changes in the particular two proteins of the virus have taken place. Then our collaborators identified patients who did not respond to the therapy but did not have those changes in the two proteins. When they tried to work out if there are other regions in HIV that influence becoming resistant, they found some interesting changes in the protein responsible for incorporating Vpr into the virus particle.

This is where I came in with my experience of working on Vpr, and we collaborated on trying to work out if those patients have Vpr incorporated into the virus particle. When we made recombinant viruses – that is, we took part of the virus from the patients it had been isolated from and put it into a lab strain to work out what effects the changes have – we found that Vpr is not incorporated in the recombinant virus. However, the patients have that protein incorporated. That is very interesting, because it shows that Vpr is very important in vivo, and that if changes occur which would prevent the incorporation of the protein, the virus changes Vpr itself to again get it incorporated. It is really the first time that the incorporation of Vpr has been shown to be important in vivo. And that’s about to be published. It’s very exciting.

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Exploring the implications of a truncated gp41 strain

The project on gp41 arose from something we stumbled across when we were setting up my lab at the Centre for Immunology. I have a very good research assistant, Darren Jones, who started to run initial screening tests with some of the assays that we do with antibodies, to see which of the proteins are present in the virus. And when I looked at those assays I saw that in one HIV strain the gp41 – the particular protein I had worked on in the US so I was quite used to looking at it – seemed to be shorter than in the other strains. We have tried to follow up what could be the reason for it to be smaller, and it turns out that a truncation has occurred, a stop codon has been inserted. That protein is about 100 amino acids shorter, so it is 100 of the building blocks shorter than normal. That has happened in a strain that is very widely used as a reference strain by researchers all across the world.

We received that strain from the NIH, which has a Reference Reagent Program that supplies HIV reagents all over the world for free. (You just pay shipping costs.) It appears that the truncation has happened at the NIH, most likely several years ago through continuous passage. It is very exciting to have discovered this, because at the moment that strain is used in particular as a reference strain in research with drug-resistant strains, so it is possible that researchers could come to incorrect conclusions because they are working with something that is not what they think it is. So that is also being submitted for publication next week. And it will be exciting to follow up what that truncation actually does to the virus.

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Science commercialisation: development flow versus information drought?

What do you think about the potential commercialisation of the science that you’re involved in?

The research has potential for drug development later on, and if it does lead to drug development, that’s great. Obviously, one of the aims is to find a way to fight or even cure HIV. But I am an old-school scientist, I guess: I think that all the knowledge we create and all the things we find out should not be commercialised, should not be owned by anybody. I am very wary about all this commercialisation that is going on, and about people selling off their ideas and patenting things like genes. Everybody should have free access to all the information that is found out in research at universities. It shouldn’t be owned by any company, because that keeps the information away from other researchers to build on – and that’s not a very good idea.

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Science and life: interests, challenges and rewards

Sabine, as well as your science you have many other interests, some of which go back a long way.

Among my other interests was underwater rugby – a very, very exciting sport which again involves snorkelling. (Everything I did had to be underwater!) It’s the only game I know of that is played in a three-dimensional playground: the ball is filled with salt water, so it sinks, and you have baskets at the bottom of a pool. It is rather rough. I played with the national men’s team in Austria, and it was a great time. It kept me fit and also it improved my snorkelling
skills a lot.

I still enjoy snorkelling and scuba diving. I’m a real outdoors person, and I enjoy bushwalking and also rock climbing, which my husband introduced me to. Motor cycles are my real passion. I’ve been riding them since I was 16 and I have had a motorbike on every continent I have lived on – in Austria, in the US, and here. And I have a one-year-old son now, Christopher, who is absolutely keeping me busy. He is also very curious. It is definitely a challenge to be a first-time mum and to keep a science career, but it has been very rewarding.

What have you found the most rewarding aspects of a career in science?

Even in my early childhood I always asked questions about how and why things work, and it’s really like putting pieces of a puzzle together. It has been my passion during my whole life to try to understand how, exactly, things are working. And finding out one more answer, one more piece, and adding it to the puzzle is the most rewarding experience in science.

Another thing that I really enjoy is teaching, passing on the knowledge to students. That’s also very rewarding.

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Building a future on skills and passion – and funding

What skills are most needed in taking up a career in science today?

It’s increasingly important to be able to keep up with all the information that is out there, so computer skills and knowing the internet, knowing where to get information, are important. Good communication skills and writing skills are also very important.

But the very most important thing for a career in science is to just have a love for it. You have to have a passion for the job, because there is not much funding for science and not much money in it. So you really have to love what you’re doing – you have to be curious about what you’re doing. That, I think, is what gets you there.

Sabine, having achieved such a lot in such a short career, where do you see yourself in 10 years’ time?

On good days, I’d love to be still in research in 10 years, with a bigger lab, more students and more research assistants. But on bad days, when our grants aren't successful, I think I might be teaching scuba lessons or working for a museum, or be a stay-at-home Mum – I have no idea. I’ll have to look at something else if I don’t get funding!

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