Twist of Fate

Developmental biologist Dr Alison Woollard tells Tom Ireland about her Royal Institution Lectures, and how cells know what to do

The Biologist Vol 61(2) p30-33

Dr Alison Woollard FSB is a dean and lecturer in genetics at the department of biochemistry at the University of Oxford and a Fellow of Hertford College, Oxford. Her extensive research on development in worms led to her being asked to present the famous Royal Institution Christmas Lectures last year.

The Royal Institution Lectures have been televised on the BBC since 1966 and were first held in 1825. What was it like presenting them?

It was absolutely all-consuming, from October until Christmas. The Royal Institution decide a rough area with the BBC and approach a range of people that haven't really done a lot of presenting before. My first reaction was, "Oh, I can't do that," and I actually deleted the email. Then they prodded me a bit later and I thought it would be a really good thing to do.

Do you have plans to do any more TV work?

I do now! I realise it's something I really enjoy doing and is really important to do.

Do you think the average member of the public knows what a cell is?

No, I don't think they do. There are a lot of misconceptions about the relationship between a cell, a gene and DNA.

Is it important that they do?

I think it's really important, especially as we move towards cell and gene-based therapy, whole genome sequencing and personalised medicine. We need to understand what they involve and realise that they aren't a panacea and that there's huge complexity in genetic disease: it rarely involves just one gene.

Having started an environmental sciences degree, how did you end up studying developmental biology?

I was very active in the environmental movement, but quickly realised it was pure sciences that interested me and so I switched to biology. I did my degree at Birkbeck College in London, which only does part time courses so was a great melting pot of people studying biology for all sorts of reasons, such as people close to retirement who'd always harboured this secret curiosity. A couple of them contacted me to say they saw me on TV. Their last memory of me was probably doing some hopeless practical one evening.

You now study cell proliferation and cell specialisation using the nematode worm Caenorhabditis elegans. How did you get into that?

When I started my PhD, I was interested in the control of cell replication – quite fundamental biology that controls how all cells divide, and we [Woollard worked under Nobel Prize winner Sir Paul Nurse] worked on single-celled organisms such as yeast. The genes that regulate replication in those organisms are pretty much the same as those in humans. That showed me the power of using model organisms.

Then, I wanted to work on multicellular organisms to look at how cells become different too. It started to interest me how cells know what type of cell to become, and when, and in the right place, in the 3D architecture of the body.

C. elegans was the perfect mixture of complex and simple – it only has 1,000 cells [Woollard can identify every single one]. That means you can study development at single-cell resolution. If something goes wrong, you can find exactly which cell malfunctioned and at which stage.

What have you been working on with C. elegans recently?

We focus on a type of cell called seam cells. They have stem cell like properties and their daughter cells specialise differently. The anterior daughter normally differentiates and the posterior daughter continues dividing, which means you end up with an interesting asymmetrical development.

How do entire tissues and body plans form from individual cells?

Well yes, we look at not only how cells know to be heart cells, but how they know where the boundaries of the organ are. There's still so much left to find out about how they do it. It involves molecules being produced in one cell that will move and influence another one.

When you have to work out which regulatory proteins regulate which genes, and then which genes code for the regulatory proteins themselves, and what proteins regulate those genes and so on, where on earth do you start?

I know – it's an absolute morass. We know it must start with signals that an embryo gets from the mother. There are proteins deposited in the egg in a particular pattern that sets off this chain reaction of genetic events that is development. However, then you have to ask, what's regulating the sending of those signals in the mother?

The most common way to get answers to these questions is to use mutants that have a defect in the process that we're examining. If you're interested in a signalling pathway involved in making intestine, you can look for that in worms, because they have a gut. Alternatively, if you need to look at a heart, you can use a zebrafish.

What are you most proud of in your career so far?

I think isolating genes, which we can work on in a simple system, that are applicable to higher organisms. A lot of my work feeds into cancer research; we're still at the basic biology stage rather than it translating into therapies. It's likely to be that way for a while, purely because when you have this morass of genes, it's important to find out which are the real drivers of these processes and which are just tweaking or assisting them. Sorting out that is incredibly challenging even in a simple system.

How important has Nobel Prize winner Sir Paul Nurse been to your career?

He's a huge inspiration. He's very good at picking out the significant experiments to do. There are all these experiments that you could do, but only one will move you forward – and he knows which one. And he's very normal; his sense of humility really comes through. It was great to have Paul appear on my Christmas Lectures [he rode into the studio on a bike with pedals instead of handlebars to demonstrate the effect of a developmental defect].

Why do you think there's such a sharp drop-off in the number of women going into senior scientific roles after postgraduate level?

It's hard to say. I find it a constant challenge juggling family and work, and I do think women feel it more deeply than men.

It can become a conflict because academic science is an absolute treadmill. You've got to keep publishing papers and applying for grants, and it's incredibly difficult to slow down. I would love to have gone part time, but I would have just ended up doing exactly the same job for less money.

I was very torn between being a good mother in the early stages and keeping my lab going. On balance, I do feel I would have liked more time to be the mother of a new baby.

What can research institutions do to help?

It's hard to know if it's something universities can do anything about, because it's about the entire funding system in general, the meritocracy of science. These problems are intensified in science. I can talk about the problems, but I don't have any solutions. I think I benefited from the fact that I didn't really think things through; I wasn't strategic. Maybe if I was, I wouldn't have done it. I don't know what makes it work, but I'm also sure if I hadn't had children, I would probably be more successful than I am now.

How do you juggle your research, teaching, deanship, and now TV work, with being the mother of a young family?

Badly, to be honest. The college was really supportive and people gave lectures for me during the Royal Institution broadcasts. I basically abandoned my family for a few months, which they naturally found quite difficult, but dad stepped up to the plate and they were all a bit blown away when they came to London and saw me presenting a TV programme.

Will you work with your 'heroes', C. elegans, for the rest of your career?

Yes, probably. There's a fantastic community of worm researchers, a good 1,000 labs worldwide. Every year, there's a huge international meeting in LA and a worm comedy show at the end of each meeting.

Are worm researchers better than the drosophila researchers, then?

Yeah! I think it's a friendlier community with an ethos of sharing reagents, data and knowledge.

Finally, how far off are we from understanding the entire genome – how it instructs cells' development from egg to death?

I don't know if it's possible to ever sort everything out. We probably know the real function of fewer than 1,000 out of 20,000 genes. I expect we may have found the easier ones too.

Dr Alison Woollard FSB is a lecturer in genetics in the department of biochemistry at the University of Oxford. Her research focuses on developmental biology of the nematode worm C. elegans.