United Kingdom
September 5, 2014
Continuing our series of articles on Great British Bioscience pioneers, we profile Professor Sir David Baulcombe from the Department of Plant Sciences at the University of Cambridge and his pioneering work on RNA silencing and disease resistance in crops.
How did your bioscience career first begin?
"My university tutor advised me to choose a PhD project based on what I thought was the most important question in biology. For me, it was about regulation of gene expression in eukaryotes - organisms with complex cells.
"Jacob and Monod had generated the gene regulation paradigm for bacteria but, when I started my PhD in 1973, it was all to play for in plants and animals. I considered switching from plants to animals at various times in my career but in the end stayed green. It was a good decision because plants are very good experimental systems and they are part of the single tree of life - discoveries from plants can apply across the whole of biology.
"Increasingly there is recognition that research into plants is important not only as a source of basic knowledge, but also to ensure efficient and sustainable production of food and biomaterials for many different industries."
What are you working on now?
"I am still interested in gene expression and its control but we have moved on since 1973 when understanding of any one gene was considered progress.
"We can now look at more complex questions. One of our current interests is hybrids – that is offspring of two different species or breeds. Why is it that hybrid plants and animals often have extraordinary characteristics that are outside the range of the parents? Our hybrid project is heavily influenced by epigenetics – the study of heritable effects that are affected by chromatin structure rather than the sequence of A,C,G and T in DNA. For these projects we are using the tomato and Chlamydomonas (a species of algae). Tomato is used because we can make interspecific hybrids between cultivated and wild species. It is also a crop and our findings will influence plant breeding as well as basic understanding of hybrids in natural evolution. Chlamydomonas has a short life cycle and allows us to look at effects over many generations more easily than with a higher plant.
"In other projects we are interested in disease-resistant plants. We are trying, for example, to provide a GM solution to Maize Lethal Necrosis Disease (MLND) which is a serious threat to maize crops in East Africa. I am committed to help make agriculture more sustainable using our research."
What advances have you seen in your chosen field in the last 20 years?
"The most significant advance over the last 20 years has been genome sequencing. DNA sequencing technology has advanced enormously over the last seven years and now it's relatively routine to complete the genome sequence of any plant.
"One of the most important benefits of the DNA sequence revolution was in gene mapping. When I started my career, it was very difficult to identify the genetic elements that affected the characteristics of an organism. Even as recently as the 1990s it took a lot of time and effort to identify a disease resistance gene but, with genome sequences in 2014, we can do it in weeks.
"The availability of genome sequence also means that biologists can ask much more open-ended questions than twenty years ago using molecular biology. At that time we could study the influence of small groups of genes on a biological process, but now we can ask questions about the entire genome. We are beginning to understand how it is that the whole of a living system is so much more than the sum of its individual component genes."
What are the key bioscience milestones that you've been part of?
- 1999-2004 – Small interfering RNA The biggest discovery by my lab was made by a postdoc- Andrew Hamilton. He identified a new type of regulatory RNA that is now known as small interfering RNA. There is the exciting prospect that small interfering RNAs can be used for disease therapy in animals including humans and for crop improvement.
- 2001 – RNA and epigenetics Louise Jones, a postdoc in the lab, demonstrated that RNA could direct epigenetic changes in plants that are inherited from one generation to the next. The discovery will help us understand how nurture or the environment can change the nature of an organism or its progeny.
- 1997-2010 – Mobile RNA Olivier Voinnet was a PhD student in the lab when he discovered that RNA moves between cells or even long distances in plants. Signalling molecules are conventionally small and their specificity is normally determined by protein binding – a signal would bind to one or a few proteins in a highly specific manner. RNA in contrast is a completely different and much more flexible type of signal. It finds its target by Watson Crick base pairing and could be tailored or have evolved so that it targets any gene.
- 1985 onwards – GM virus resistance My group pioneered virus resistance in transgenic plants and our first successful experiments were published in 1985. We have now refined the methods and the current technology could be applied to any crop and any virus.
How has BBSRC supported you throughout your career?
"BBSRC has been a great sponsor through various responsive mode grants which have enabled both myself and my team to continue our pioneering work."
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