Dr Elizabeth Dennis is an eminent plant molecular biologist and a Chief Research Scientist working in the Division of Plant Industry of CSIRO in Canberra, where she leads a large team of research workers. Her work has been recognised by many invitations to speak at international meetings, and she is a past president of the Australian Society for Biochemistry and Molecular Biology. She was elected to the Australian Academy of Technological Sciences and Engineering in 1987 and to the Australian Academy of Science in 1995. In 2000, she was joint recipient of the inaugural Prime Minister's Science Prize.
Interviewed by Professor Frank Gibson in 2000.
Dr Elizabeth Dennis is an eminent plant molecular biologist and a Chief Research Scientist working in the Division of Plant Industry of CSIRO in Canberra, where she leads a large team of research workers. Her work has been recognised by many invitations to speak at international meetings, and she is a past president of the Australian Society for Biochemistry and Molecular Biology. She was elected to the Australian Academy of Technological Sciences and Engineering in 1987 and to the Australian Academy of Science in 1995.
Do you think something in your family background, or perhaps your schooling, Liz, led you to choose to study science?
I come from a fairly middle-class family. My father was an engineer; my mother worked on and off while she was looking after the kids. We lived in Hunters Hill, in Sydney – quite a nice suburb, if a little bit ‘bohemian’ in those days (but much more up-market now). A lot of interesting people lived there.
I was the eldest of three girls and my parents were very supportive of any academic aspirations I had. I think my father would have liked me to be an engineer, like him and his father before him, but I always had the expectation of going to university and then following a career. I went to Methodist Ladies College, a girls’ private school which was very good, and unusually supportive of women. Its philosophy was that you shouldn’t not do anything because you’re a woman, and so it provided courses for us like physics honours and chemistry honours, which were unusual then.
As a young girl I was always keen on chemistry. Reading stories of Madame Curie, I decided I wanted to be like her. I think she was the only heroic figure I had in my early childhood. Then at MLC we had a very good chemistry teacher – she had a PhD in chemistry, and was outstanding in those days – who gave us a real interest in chemistry.
Would you tell us about your university years? Did you find your undergraduate course – majoring in chemistry and biochemistry – very satisfying and stimulating?
Intellectually, in general no. There were huge numbers of people at Sydney University then : we’d have a lecture of 1000 people and virtually no stimulation by the staff or contact with them, in the first couple of years. I’d say the undergraduate teaching was very poor, except for the ‘odd’ courses. In first year we had Hans Freeman, a very exciting lecturer, for a special chemistry course. And then Harry Messel and Stuart Butler – both exciting – ran a special physics course. In second year, hearing Gerry Wake talking about nucleic acids made me decide that was what I really wanted to do, and later one of the best things that happened to me was having Gerry as an honours supervisor. He taught me a lot about science, about being rigorous, about being focused and methodical.
I went on to do a PhD with Gerry at Sydney in nucleic acids, on how bacteria replicate their DNA. Then I went to New York to Julius Marmur, who was one of the pioneers in physical studies on DNA. He had worked out the relationship between base composition and melting temperature of DNA and also base composition and density in caesium chloride gradients, and developed one of the early methods for preparation of DNA from bacteria. So he was really a bacterial DNA expert, but when I was there he said, ‘Well, what do you want to work on?’ It was very laid back. I looked around and saw they’d started to work on mitochondrial DNA replication in yeast, a natural progression from the bacterial DNA replication work I’d done with Gerry.
During this period you were fairly socially conscious and got involved, I gather.
Yes. The late ’60s was the time of all the civil rights activity and later the anti-Vietnam days. At Albert Einstein College of Medicine, in the Bronx, I found a very active group of doctors, students and post-docs keen on those issues, but also worrying about civil and medical rights for poor people, blacks, and other disadvantaged groups. That whole swag of social issues in New York at that time opened my mind.
Perhaps because of this social awareness, you didn’t come back to work on DNA, did you?
No, I went to lecture at the University of Papua New Guinea. This may be a paternalistic view, but I thought it was good to do something to use your knowledge for the less developed countries. That was quite a mind expanding experience. I think normally we are comfortable in our own little niches, but Papua New Guinea didn’t have all the molecular biology, high-tech instrumentation and big infrastructure, or an environment where you can feed ideas off lots of colleagues.
I was doing chromosome and DNA studies on the native rodents, and together with a classical zoologist, Jim Menzies, I would go out trapping rodents and taking pictures of them and determining the chromosome complement. We even wrote a book on the rodents of Papua New Guinea. There is a big radiation of species. Some of them are cute little tree mice but one rat is called Hyomys goliath because it’s so big (about 400mm head and body and tail the same weighing 1kg). And they’re quite unrelated to Rattus. That project was fun and I saw a lot of the PNG countryside. Doing this work taught me that there are a lot of scientific problems and it’s interesting when you get involved in any of them.
Later you moved to the CSIRO Division of Plant Industry, in Canberra. Were you pleased that that meant you were able to get back to your beloved DNA and to develop a long-term research program?
Yes. At first, I worked with a very good group under Jim Peacock’s leadership, including Doug Brutlag and Rudi Appels. We looked at repeated DNA in Drosophila. Then I returned to Papua New Guinea for a while. When I got back to CSIRO, in 1976, the mission of Plant Industry had become more focused on plants, so we switched over – still in conjunction with Jim – to working in DNA from plants.
During the ensuing years you’ve covered several topics. Could you tell us something about the work on haemoglobin? That doesn’t sound very plant-like.
No, it doesn’t. That was quite an exciting development. It was inspired by Cyril Appleby, who is also a member of the Australian Academy of Science. He worked on haemoglobins, initially from legumes which use haemoglobins to carry oxygen past the bacteria involved in symbiotic nitrogen fixation. Then he isolated and worked on a haemoglobin from an Australian tree called Parasponia, which also fixes nitrogen. We decided we would clone the Hb gene Parasponia. It was known, as the basic principle, that haemoglobin is important in fixing nitrogen in the nodules of legumes and that other Australian trees also fix nitrogen. The question was whether the gene that is used in the non-legumes is the same as the gene used in the legumes. So we isolated genes from other species – in the beginning, from plants in Australia and Papua New Guinea like Casuarina and Parasponia, which fix nitrogen.
We found that in fact there were two quite different Hb genes, one that was in the legumes and also in Casuarina, and another one in Parasponia that was quite different. But we then found that the gene in Parasponia was also present as a second gene in Casuarina, but not in the nodules. It became clear that there were two families of Hb genes, each of which had been recruited to fix nitrogen, one in the legumes and one in the Parasponia. We then went on to show that in Arabidopsis, which has nothing to do with nitrogen fixation, there are two classes (and now possibly a third) of plant haemoglobins. We have extended this to suggest that Hbs are in all plants. They’re related to the animal haemoglobin, so they’ve probably been there ever since the divergence of animals and plants about 1500 million years ago. Hbs must have had some function other than nitrogen fixation in plants, and then subsequently, as the legumes and Casuarina and other nitrogen fixing plants evolved, the haemoglobin genes that were there became adapted to function in nitrogen fixation. If you cut open a nodule on the roots of a pea, you find it’s quite red because it’s got haemoglobin in it.
We’ve been trying to work out the function of these Hb genes in plants and the only thing we’ve found so far is that one of these genes in Arabidopsis is switched on by low oxygen. In fact, if you put more of that Hb into the plant, it protects the plant against low oxygen stress. So that may be the function of one, but we have no idea what the function of the other one is.
How long have you been working on that problem?
For 15 years, on and off, mainly working with students. As new techniques become available, we go back and try again. Of course, all the work is a lot of collaboration with different students and postdoctoral fellows.
You also have an interest in the flowering of plants. In general terms, what is that about?
That is very much our current project, involving all the people in the lab. Flowering is an important developmental process in plants, a very exciting biological process. In animals you set aside your germ cells early in development, but in plants there is a growing point which starts by making leaves and stems and vegetative structures but then switches to making reproductive structures like flowers and pollen, all the components that make up flowers. So how does that switch occur? How do cells derived from the one growing point change from making vegetative to reproductive cells?
Using Arabidopsis, we isolated a mutant that didn’t flower till very late, and then we isolated the gene that was mutated to cease this effect. We could show that this gene acts as a repressor of flowering: the more of the gene product there is – the more the gene is switched on – the later the plant flowers. It’s a quantitative controller of flowering time. Later we found that this gene is down-regulated by vernalisation, a response to a period of cold which has long been known to cause plants to flower.
Plants need to flower in the springtime, not when there might be frosts or when they won’t have enough time to get their seeds mature for the next generation. They can’t go inside when it’s cold, so it is very important to them to flower at the right time and they’ve evolved mechanisms to ensure this happens. One of those mechanisms uses the cold as a signal. That is, many plants require a period of cold – a cold winter – in order to flower in the spring. They may also use day length (they recognise when the days get longer) as well as vernalisation to ensure that flowering occurs at the right time. We’ve found that the vernalisation, or cold, switches off the repressor gene called FLC – flowering LOCUS C. After this repressor of flowering is switched off by the period of cold, the plants flower. So we have a molecular basis for one of the long-standing question in plant biology – how does vernalisation work?
You’ve also been interested in the regulation of plant genes, haven’t you?
Yes. That’s the basic theme that makes it all hang together. The major project we’ve had, over a long time, is looking at genes being switched on by low oxygen, such as occurs in flooding or waterlogging. When plants are flooded they can’t run away. If it gets wet for you and me, we just walk away, but the plants are stuck. Plants have evolved mechanisms to cope with stresses caused by their being sedentary. So, when plants are flooded, they switch their metabolism from oxidative metabolism – oxidative phosphorylation – to fermentation. They make alcohol: the genes for the ethanol fermentation pathway are switched on. Instead of pyruvate going into the Krebs cycle, it enters the ethanol fermentation pathway where it is converted first to acetaldehyde and then to alcohol, using the enzmes pyruvate decarboxylase and alcohol dehydrogenase.
Over the years we have looked at these genes switched on by low oxygen, trying to identify the promoter motif so important for switching them on. In fact, all these genes have the same anaerobic response elements, so they all have a DNA sequence, upstream of the gene – a promoter element – that’s important in the glycolysis and low oxygen metabolism alcohol fermentation pathways. We’ve now identified the protein that binds to that low oxygen control element. That’s the sort of thing we’ve been interested in, with a view to trying to help Australian agriculture by making plants more resistant to waterlogging.
You had an interesting time at Stanford, I understand, working on gene regulation.
Yes. In 1982–83 I spent a year’s sabbatical as a Fulbright Fellow in Paul Berg’s laboratory. That helped me in several ways. For one thing, it helped me to understand the thinking that people in Paul’s lab and other labs in Stanford were using to try and analyse the control sequences of genes. They were further advanced toward understanding the sequences that replicate genes. To introduce a candidate you introduce it back into animal cells, see what effect that has, irradiate mutate a few bases, and see if this alters expression of the gene.
But also, the whole way the Stanford biochemistry department worked was very good for me in considering how laboratories, departments, could work. That department was very distinguished: two Nobel prize winners were in it – Arthur Kornberg and Paul Berg – and maybe three-quarters of the rest of the faculty were in the National Academy and really were very innovative and exciting scientists, like Dave Hogness, Ron Davis and Dale Kaiser. Charlie Yanofsky, in biology, was around there too. The department was small, with only about eight or ten members of staff, but the way they worked together produced a very exciting intellectual environment. They had staff meetings where they discussed science and the department, they pooled their grants, they worked together, they didn’t try and look after their own equipment or prevent other people using them. Everything was cooperative, which seems a very good way to work.
Over the years, in your various activities, you have made quite a few novel discoveries. As a result, you have been invited to talk at many international meetings.
Well, it’s been the right time, with the new techniques in Arabidopsis and new expression techniques in plants, for us to identify what the sequence is controlling the genes switched on by low oxygen. The completely unsuspected idea that there are haemoglobins in all plants is also a novel discovery, and then this gene that regulates flowering, that we’ve recently been working on, is pretty novel too.
A lot of this work has been done in collaboration with other people, and so we share around the talking at international meetings. And I’ve had a long-term working arrangement over these years with Jim Peacock, who has had a big input into projects.
Would you say there have been major switches of your research direction at particular times? If so, what caused them? Which gene did you switch on?
I think changes in direction come with the opportunities provided by new techniques. The advent of cloning, of being able to isolate genes, has certainly been important. Initially we worked on repeated DNA in Drosophila and in plants. The Drosophila DNA and also one of the plant DNAs have the sequence like AAGAG, and it took us about 3 years to sequence those five bases! This little five bases repeat was repeated maybe a hundred thousand or a million times, but to actually get that sequence – back in the middle 1970s, with Doug Brutlag and other people – took a long time. But then the ability to sequence DNA, and later, cloning, enabled us not just to look at repeated DNA, but to isolate the genes and to study them in detail. The technology has been tremendously important. The development of Arabidopsis as a model plant, with its genome now almost completely sequenced, has been very important in plant molecular biology. So often, it seems, we spend years doing something that appears really simple afterwards!
You have also applied your interest in biotechnology to rice, in a very important project. Has the outcome been satisfying to you?
This project built on our work on haemoglobin, a protein that has a haem group, which binds iron.
People in developing countries who eat rice as their major food source face two major problems of nutrition. One is that people can go blind from vitamin A deficiency, and the second major problem is anaemia. Rice doesn’t have much iron, so something like a billion people suffer from iron deficiency anaemia. One of our projects, with support from CSIRO and from the rice growers of Australia, has been to try and increase the iron content in rice. We’ve added genes for haemoglobin under the control of strong regulatory sequences so that they’ll have high levels of activity in the seed and the seed will contain large amounts of haemoglobin.
So we’ve got transgenic plants with high levels of haemoglobin, but we don’t really know how much that has done for the iron, because it’s very important how iron is presented when you eat it. If it is associated with haem, it’s much more bio-available and can be absorbed: it can be 20 times more efficient than if you just eat the same amount of iron as iron filings or ferrous sulphate. So we’re starting feeding trials on rats – and there’s an artificial system now – to see whether we have improved the nutritional properties of the rice as far as bio-available iron genes.
The problem of the vitamin A has been attacked by Ingo Potrykus and other workers in other parts of the world, and you may have heard they have had some success in making rice that contains higher levels of vitamin A.
Apart from being President of the Australian Society for Biochemistry and Molecular Biology, for a long period you’ve been on numerous government committees and so forth. Do you regard your committee work as an act of charity or a necessary ill, or do you really enjoy it?
I guess a combination of all that. There is a duty side to it: I think we have a responsibility to put back something into the scientific community so we should do some of this, just to help. But I particularly enjoy committees which are reviewing science and trying to see what people are doing, trying to evaluate it and make suggestions for where things should go. I have enjoyed being on committees reviewing departments, or research grants committees, because I like broadening my focus. I learn from it too. That side of it I like; some other committees are more duty.
In such a very busy life, I imagine you’ve worked very hard and constantly. Do you have any outside interests at all? If so, how do you fit them in?
Well, I have a family – I guess that’s an outside interest. We have two boys, now aged 15 and 13 so they’re pretty active, and looking after them takes a bit of work. They’re probably not looked after as well as they might be, but they seem to be pretty tolerant about having a mother that’s a scientist, and the idea of my having to work. Most nights, I come home, make dinner, have a bit of family life and then go back to work about 9 or 9.30 and work till about 11 or 11.30.
My other major interest is that for just on 20 years a group of us have owned some land on the coast, at Tilba. It was a dairy farm, so it had been completely cleared – there was only one tree left on the whole 70 acres. We do a lot of tree planting and revegetation, and have enjoyed seeing what happens when you restore the vegetation, watching what birds and animals come back. It’s right on the beach, so it’s also a very nice place to be: it is very relaxing to enjoy the botany and wildlife and have a swim. Next to us a national park has been declared, so we’ve been active in getting it protected, stopping people from driving on its dunes, and revegetating those dunes too. That’s been very important, and to have that break away from work does help – no telephone, no electricity down there.
You have some pretty firm theories on what should be taught at university, and how.
I really enjoyed university, but largely because I lived in Women’s College and so I made quite a lot of close friends. We’d spend time discussing the meaning of life and the intellectual basis of ideas. In the days when I went through university, it didn’t develop people’s capacities to their full or take full advantage of their abilities. I would have preferred smaller groups doing projects, where people actually focused on things that they needed to know – trying to work from a project-oriented base rather than having a vast amount of knowledge that had to be just stuck into you. Kids now are not reading anywhere near as much as they used to, but they are very computer literate and they do learn in a much more empirical way than we used to. I think that education could change quite a lot towards taking advantage of the flexibility of younger people and their ability to pick up things as they need to know them. If you can give them a project where they need to know things, and they go out and find them, that is a much better way to learn.
I learnt a great amount of organic chemistry that I’ve completely forgotten because I’ve never needed it again. I think that very classical view of education we’ve had should be changing, but I can’t see many of the universities responding to that.
There has now been another change in biology, into genomics: instead of looking at single genes, we have to look at whole genomes and see all the genes that are changing and what’s going on. That’s much more information-rich and information technology-rich science and again has a much more empirical basis. You might start off with a hypothesis, but part of the question will be, ‘What gene is switched on?’ rather than, ‘Let’s test if gene X is switched on.’ So the science is discovery-based rather than hypothesis-based. You might find a lot of new parameters that you didn’t even think about. If you start off in the traditional way you say, ‘The genomics approach means that you’ll find X, Y, Z and others that you’ve never even thought of’. It is a much broader view of science than we’ve been used to.
You talk about the genomics approach. Presumably you’re thinking now of actual research work rather than instruction?
Yes, that’s right. But if we’re instructing people so that they can use the new science, we have to encompass this new approach to research in the teaching as well. There are two pressures for that. One is the sort of research that’s being done, and the second is the sort of background the kids coming to university have now, which I think is very different from what we had. We were all reading a good deal but had a narrow base of experience. But I think kids come now with a much broader background – not as intent on reading, much broader because of the computer and the internet. And so instruction has to change too. The way to link those two things is to give them at least project-based work: not ‘Here’s a mass of knowledge, learn it,’ but, ‘Think about doing this, and find all the things that need to come out of it.’ There’s so much knowledge, you can’t hope to learn it all. How do we decide whether we should have five hours a week organic chemistry, or one hour a week? What’s the basis? What is the body of knowledge that should be passed on? We don’t know.
Thank you, Liz, for giving us so much insight into your experience and your ideas.
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