Dr Moira O'bryan, medical scientist

Medical scientist

Dr Moira O'bryanDr Moira O’Bryan, despite her youth, has already made a major contribution in the area of molecular reproduction and endocrinology. She started her career at St Vincent’s Hospital, in Fitzroy, Melbourne, working on the characterisation of an immune regulator in the male reproductive tract, and its effect on infertility. Awarded a Mellon Foundation fellowship at the Population Council Centre for Biomedical Research at the Rockefeller University in New York, she worked there on the endocrinology behind male fertility for three years. She then returned to Australia, to the Centre for Molecular Reproduction and Endocrinology at the Monash Institute of Reproduction and Development, Monash University, in Melbourne. Here she heads a large research group, the main projects of which revolve around identifying components of the mammalian sperm tail, identifying their function and determining if they are associated with human male infertility.

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Interviewed by Ms Nessy Allen in 2001.

Contents


Introduction

Moira O’Bryan, despite her youth, has already made a major contribution in the area of molecular reproduction and endocrinology. She started her career at Melbourne's St Vincent’s Hospital, working on the characterisation of an immune regulator in the male reproductive tract and its effect on infertility.

Awarded a Mellon Foundation fellowship, she worked at Rockefeller University in New York on the endocrinology behind male fertility. After three years she returned to Australia, to the Centre for Molecular Reproduction and Endocrinology at the Monash Institute of Reproduction and Development, Monash University, in Melbourne. Here she heads a large research group, the main projects of which revolve around identifying components of the mammalian sperm tail, identifying their function and determining if they are associated with human male infertility.

Family influences

Moira, where were you born, and when?

I was born in 1966 in Berriwillock – a very small town of about 100 residents – in the Victorian Mallee about four hours north of Melbourne. I have one sister and two brothers, all younger than I am.

And your parents?

They had lived up there most of their lives. My father was a shearer, from a farming family. My mother was a teacher, and came from a teaching family. They were both avid readers and many was the day I came home to find that Mum had been reading all day, with a big stack of books next to her.

My parents, particularly my mother, were very supportive of education. We didn’t have the option of going onto the family farm, so I think from a very early age we knew that we would go to university when we turned 18, and we would probably move to the city. That was fine, we were all very excited about the idea.

Were your parents supportive of science in particular?

They had a very strong interest in it, probably Earth sciences rather than laboratory sciences. My mother and my grandfather certainly had a very strong interest in geology. They were both keen gardeners and we would often go on Mum’s ‘nature walks’ – we hated them at the time, but in retrospect I suppose we began to notice things and learnt quite a lot.

Mum was from a very large family of 11 children, and one of her younger brothers, Patrick, was actually a geneticist. He would have only been about seven years older than me, and through him I encountered genetics, which I found very exciting. I can remember going into the laboratory where my uncle was doing his PhD when I was maybe 13 or 14, and thinking that what he was doing was fabulous. (I can’t remember what the experiment was, but I know he was counting flies with red eyes and flies with white eyes.) He was ‘discovering’ things, whatever that was!

But I suspect the strong influence on me came from the family, rather than one person in particular.

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The dawning challenge of scientific research

What science subjects did you take at school?

At secondary school I did all of the standard ones – mathematics, chemistry, biology, physics. The school was very small so there was a fairly narrow range of subjects available, but I took all the science I could, rather than, say, accounting and so on.

Were the teachers encouraging?

One in particular, Alan Marshall, was very supportive. When I found science quite easy at school he went out of his way to challenge me, giving me extra assignments and interesting books to read, for example. Fortunately for me, the classes in such a small school were also very small – in my HSC physics class there were three people – so I had a lot of individual attention, which was fabulous.

Did you know what you would want to do at university?

When I finished high school I knew in general that I wanted to do science. I remember saying I wanted to be a biochemist but I didn’t really know what that was, and it wasn’t until I actually went to university that I found biology the most enjoyable of the four basic areas of science. Perhaps that’s why I found it easier and stood out in it. That was when I realised I would probably end up being in biology, and fairly early in my university career I became certain I wanted to do research.

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Honours project: clusterin interactions with the immune system

You read for your Honours in 1988 at St Vincent’s Hospital, in Fitzroy. Why there?

I remember sitting in a meeting where all the potential supervisors read out the projects – some sounded terrible but several sounded interesting, particularly the one at St Vincent’s with Dr Brendan Murphy. In the end I took that project because when I went to his laboratory to see him, he made me feel very welcome, giving me papers to read, introducing me to people, and I felt comfortable with him. So that’s really why I went to that lab.

Can you explain the work you did for your Honours thesis?

I had to purify, from blood and also from seminal plasma, a protein called clusterin, which Brendan Murphy had discovered a few years earlier. After purifying that protein we then had to find out how it interacted with the immune system. And we showed how it did, which was lovely – we went on to write that up into a paper which was published. I was very proud of the fame!

Did you then go straight on to your PhD?

No. I organised to do my PhD but to delay it while I took a year off. For about six months I worked as a research assistant in that same laboratory, actually on the same project, but after that I went travelling for six months, to Nepal, Thailand and Malaysia. I had a fabulous time. And I now recommend to my students that they take some time off, get a bit of distance. That year gave me time to decide this was what I really wanted to do, so when I came back I was motivated, I was pretty fresh, I’d had a break – I knew why I was there.

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PhD project: clusterin, male fertility and highly motivated patients

What did you work on for your PhD?

My PhD was again on clusterin, characterising where it was made in the body – specifically in the male reproductive tract – and just how it was involved in normal male fertility and how it was changed with different types of infertility. That involved a mixture of pure biochemistry, where I was purifying things, using big columns and what not, and quite a lot of clinical work. I had to go and see the patients of my other supervisor, Gordon Baker, talk to them about what had gone wrong with their fertility, get samples and then go back to them and say, ‘This is what I think is wrong,’ or ‘This is the information I’ve found out.’ I hoped that would help them, but I don’t know if it did. They were always very appreciative, though.

To have such face-to-face contact with patients was a very satisfying part of that project. They were a very highly motivated group of people, who did the most amazing things to try and achieve having children.

At about the end of 1993 you were awarded a postdoctoral fellowship.

Yes. It was a fellowship from a United States foundation supporting research into population control. So I went to the Population Council, at Rockefeller University, on Manhattan in New York – a fabulous place to work. My project was to purify a cell type from the testis, grow it and then look at what these cells were making. Again it involved a lot of biochemistry and a lot of growing cells and so on. It was a great time. I loved being there.

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Mentors and a mind-blowing place to work

Did you have any mentors during your university years, or in New York?

My two supervisors, Gordon Baker and Brendan Murphy, were excellent mentors, in that they were very kind men who really went out of their way to help me. They cleared a lot of paths and put me in contact with the right people. Perhaps they saw abilities in me that I hadn’t realised I had.

In New York I don’t think I had a mentor, but Rockefeller was a very inspirational place to work. It is quite an amazing university – no undergraduate research but perhaps a thousand postdoctoral scientists, mostly from outside of America. At that time there were six Nobel Laureates on staff. It was absolutely mind-blowing to be in an environment of scientists working at such a pace, in such a well-respected place with so much money. It was a very contagious place to work: you wanted to work harder, to achieve more. I think that’s when I got hooked on science!

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Enjoying collaboration

In 1996 you were awarded a National Health and Medical Research Council Peter Doherty Fellowship to return to Australia. Where did you take that up?

I came back to Monash Institute of Reproduction and Development, specifically to the group headed by Professor David de Kretser at Monash University, in Clayton. The Institute has grown in its 10 years from maybe 30 people to over 200, and it continues to grow. I may be a bit too close to the Institute to judge, but I think it’s a rising research centre that is becoming more and more important in Australia. Like Rockefeller, it is a very vibrant place to work – a lot of energy to get things done, a lot of collaborations between people, and a real pride in actually producing things at the end of the day.

I love collaborating with people. There are several scientists I work with constantly, and I think it’s true that two minds are better than one for a lot of things, particularly when you have students involved. Students can take up a lot of time and they do need – and deserve – a lot of attention, so if you have two supervisors or two people collaborating on a project, that is certainly better than one.

In just five years since returning, you have been promoted to senior scientist within the Institute, and I believe you now head a large research group of your own.

Yes. It certainly keeps me very busy. I currently have four PhD students, two research assistants, a postdoctoral fellow and a visiting clinician. Most of them are working on areas involving how sperm tails develop and how they move, but there is a spread of interests across reproductive biology. The PhD students are not as much work as they might have been, because they are very clever, they work very hard and they help each other – which is great for me.

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Research projects, teaching and student assistance

What types of projects are you working on, and what do they involve?

I decided to divide the research into two main areas. Most of my students and staff work on rodent models of infertility, trying to find the genes that are important to enable sperm to be made. We will look for mutations in these genes and see how they affect sperm movement, for example, or sperm number. As a natural progression, we want to find out whether those proteins we have identified in the rat or mouse are important within human males. The clinical fellow and I spend a lot of time screening infertile men for mutations, to see if we can actually tie the rodent work with the human work for a story that fits together nicely. It happens sometimes that it does.

You mentioned PhD students. Do you teach at all?

I do very little undergraduate teaching. All of my teaching is for Bachelor of Science (Honours) students, in their fourth year, or PhD students. I very much enjoy working with them, particularly Honours students. They have a lot of theoretical knowledge from their lectures but they have spent very little time in laboratories, so when they first get in there, they are amazed by how much fun it is. And the first time they find a result that they’re the first person to know, they get so excited.

I sit on a postgraduate student committee. I’ve been quite lucky that there haven’t been any problems yet with my students, but with so many PhD and Masters students going through the Institute, problems are going to happen sooner or later. The committee monitors how the students are progressing: are they getting enough supervision, are they trying to do experiments that are impossible, are they likely to be able to write up papers, will they get jobs when they’re finished? And, of course, personality problems can always pop up as well. So the committee is important in watching for problems and trying to solve them, or at least to find a way around them.

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Sharing experience, exchanging insights

Are you involved in many committees and societies?

Well, I sit on lots of committees within the University. As for societies, one that springs to mind is the Australian Society for Medical Research, which was formed to represent the interests of medical scientists throughout Australia. It monitors things like pay scales, and gives information to government, but one of its most important roles is to help explain medical research to the public. It’s very easy when you are a scientist to get tied into your chemicals and your fancy names, but the public – which is investing so much money in medical research – has a right to know what is actually being done and to insist that it will eventually help public health. So this society is there to increase public awareness and explain some of the difficult situations.

I’m also a member of several research societies, including the Endocrine Society of Australia and the Australian Fertility Society. They usually have a conference once a year which I go to with my students and they will present their work.

So you are acting as a mentor to them?

I suppose I am, in some ways. I’m not sure they enjoy it, though!

Aren’t you convening a large medical research symposium to be held in December?

I am. It is called ‘Reproductive Genomics’, and concerns the way the whole genome – every gene in your body – affects how fertility is manifest. We are looking at both male and female fertility. Setting up this conference has been a real exercise in organisation: some things I felt would be easy have been hard, and vice versa. I have been very pleased that when I have invited some very high-profile national and international scientists, they have almost uniformly said, ‘Yes, I will be there. Just tell me what you want.’ It’s been a lovely experience.

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Pure and applied research: equally important but inevitably divergent

Do you see a great difference between pure and applied research?

I think up to a certain point they are exactly the same thing – you must have the pure or discovery research to actually get some applied research. After a certain point, however, they can diverge, as we have found a couple of times. Your research instinct may say, ‘Right, I’ve finished this chapter, I’ve written my paper – tick. Let’s go and work on another little bit,’ but with the applied research you need to develop a test so a doctor in the clinic can measure the same thing you have done in a laboratory. Similarly, you may need to move into clinical trials or to test on something else. Both pure and applied are equally important, there are just different skills, and it all depends on the time and the project.

How would you describe your own research?

At the moment, it is mostly basic research – finding out a little bit of biology and extending on it again and again. But increasingly, particularly with the association to the clinic, it is becoming applied. I have to develop tests for mutations that someone else can do in the room down the corridor, or in a hospital across the country. And I have to package them in forms that will work every time, not just in the right lab on the right day.

I am interested in the practical applications of my research. I still enjoy dealing with patients, particularly in male infertility. Very few doctors actually know a great deal about it, so if we can develop products or tests that can help treat infertile men in Darwin or central Australia, that’s fantastic.

A major emphasis of Moira's group is to identify such mutations and determine the consequences for overall fertility and on any children conceived through assisted reproductive technologies.

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The search for a funding balance

Where do you get your funding from?

It is virtually all from the National Health and Medical Research Council of Australia, the major funding body for medical research in the academic community. We also have a little bit from Andrology Australia, which was set up to look at research areas within men’s health, spanning prostate cancer to infertility to heart disease and public education. And we get smaller amounts of money from international funding bodies like the Wellcome Fund and some American foundations.

How do you see research being funded in Australia in the future?

Although there have been some significant improvements with the National Health and Medical Research Council and also the Australian Research Council, doing basic research in Australia has become much more expensive – largely because of all the new technologies that have arisen out of the Human Genome Project. The techniques are incredibly beneficial and you get huge amounts of information out of one experiment, but they are also incredibly expensive, so unfortunately for scientists the government probably can’t fully fund research projects. We are virtually being forced to go and talk to industry and look for offshore – or onshore – investors, moving more and more towards a commercial setting.

That is likely to be a good thing, but totally commercial-based funding could be very bad: you wouldn’t discover accidental things while you were doing the research, ‘playing’, if you like. It is important to keep a balance of the two. And I think there will be some big changes in the next five years. Hopefully, they will be for the better, but I really don’t know.

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Exciting times, essential changes of focus

I think you and some colleagues are in the process of setting up a biotech company to explore commercial applications of your work.

We are. We argue daily about the name, so there is no name yet! The company would be based on the intellectual property that is generated from our academic research. We are at the stage where we are putting it into a neat package, and within the next six months we will look for both investment partners and other academic partners – in Australia and overseas. We want to be big enough to form a critical mass, to be able to make products that can be tested and marketed effectively. So it is an exciting time.

The company will most likely end up mixing research with being a commercial outlet for our work. Most of the research we have done through the Institute is at a point where a little bit more needs to be done before it can be channelled into a commercial stream. So the company I imagine will do a little bit of basic research and from there do product development and testing.

Do you think the setting up of such a company will make a difference to the type of research you are doing?

It probably will. It has pluses and negatives. I think it will make my research more efficient, in that there is a real benefit in setting solid goals that people can strive for, particularly if you can give a bonus when they actually get to that. There could be a negative for some of the research that might have resulted in interesting peripheral findings – someone like me might come along and say, ‘That’s not going to end up as a product. You have to drop it.’ It’s early days, so we are still working it out. I’m not sure if it’s going to be a good thing or bad, but they’re new tricks and I think they are essential things for us to do.

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The skills that matter, the gender issues that don’t

What skills do you think are needed in science these days?

Good computer skills are essential. I have a student who is a fabulous scientist, an excellent geneticist who did genetics and Arts at university, with a little computing stuff in the middle. You need computer skills more and more, and you need to be organised and also to be able to look across disciplines. I think the days of being someone who works on one molecule for your entire career are gone. You must be able to link things together and work in teams – being a team player is very helpful.

Have you found that being a woman scientist has made any difference?

No. That may be luck, in that it absolutely hasn’t been an issue for either my PhD supervisors or the professor I work for now. I can’t remember feeling any form of discrimination against me. If anything, being female has actually helped me – certainly some older female scientists have really gone out of their way to help me.

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Whither tomorrow?

Where do you see yourself in 10 years’ time?

It’s a very hard question. I think the next couple of years will decide where I am. If the company has any success I may move further into the commercial stream. I love doing bench research, getting in and doing experiments, but those days could well be numbered. I may end up sitting in an office all day. I really don’t know. But I would be loath to give up doing the occasional experiment.

Moira, it is clear that you have achieved a great deal in a very few years in your discipline. Thank you very much for participating in this interview, and whatever you decide to do, all the very best in your future career.

Thank you, Nessy.

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© 2017 Australian Academy of Science

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