Bringing biology to the genome

"I’d always been very impressed by the Sanger Institute when I’d visited in the past," says Allan Bradley. "The infrastructure is first class, and the big vision was clearly in place. It appeared to be somewhere that things could happen – like they can in the USA. In fact I had the feeling that John [Sulston] had set up a centre that was more integrated, stronger, and more diverse than the US genome centres."

The opportunity to lead the Sanger Institute was enough to lure Dr Bradley back from the Baylor College of Medicine in Houston, Texas, where he was a Howard Hughes Medical Institute Investigator and had established an international reputation as a mouse geneticist. He left for Houston in 1987, having undertaken a PhD and postdoctoral research at the University of Cambridge. "I knew UK science, which has, perhaps, a ‘thoughtful’ quality, while America is more proactive and go-getting. The Sanger has a blend of the two – which makes it unique in my opinion. The staff are very motivated and work very hard, but don’t have to spend 15 hours a day here like they would in the USA to get the same output."

Solid financial backing for the Sanger’s research was also regarded as a prerequisite for success by Dr Bradley. "Resources are key," he says. "In the USA, if you’re a successful scientist you’re usually not constrained by resources. This was not the case in the UK when I left to go to the USA, although the situation has changed over the last few years. But resources are not a constraint here at the Sanger – the support we’ve got is fabulous."

A new plan

Dr Bradley spent much of this year developing and refining the programme to augment the Sanger’s world-class genome sequencing expertise with new postgenomic research (see the five-year research programme article from this issue). "While working up the plan, there were two areas that we looked at very closely: ‘top-down’ and ‘bottom-up’ science," he says. "The Sanger portfolio now is what I’d call ‘top-down’ science. The institution decides to sequence the human genome or the mouse genome, and then brings resources into play to do that. Large projects such as these genomes have to be managed in that kind of way."

"So, for the new plan we want to address questions of gene function, and the institutional agenda is to decide where to place our resources to maximise our output – how to find out things about gene function in a systematic, automated and high-throughput manner."

Key to such studies of gene function, Dr Bradley argues, are banks of reagents and resources that will drive the experiments. "If we want to look at gene expression, say, and we want to do it in a top-down, systematic rather than the ad hoc way it’s done around the world at present, we’d want banks of cDNAs for making proteins or for putting on arrays. For genomes such as the human and the mouse, the resources are big and hard to manage, but to have such resources in your institution is very important. It shortens the timescale for the project – we’re in a competitive world, and shrinking timescales is important."

Bottom-up science

To bring hypothesis-driven, ‘bottom-up’ research to the Sanger, Dr Bradley proposes to recruit 20 new independent investigators over the next five years. "There is superb expertise in the faculty here, but not a lot of diversity," says Dr Bradley. "This reflects the central mission of the centre – human genome sequencing – so we want to add depth to the faculty, with a blend of seniority and expertise."

And such new expertise will help the high-throughput experiments: "Biology and biological data are not as absolute as a DNA sequence – there are shades of grey in biology," says Dr Bradley. "I don’t think that you can have a centre doing high-throughput biology without people to interpret the data, feedback to the high-throughput teams, and to take the results further."

Dr Bradley envisages a wide range of topics that could be studied at the Sanger Institute: "There are many aspects of biology that aren’t being tackled here and which we should think about: genomics, human genetics, mouse genetics, worm, zebrafish, bioinformatics," he says. "That said, our philosophy is that we’re going to go for the best individuals, so our recruitment will not be constrained by area of biology, and our goal is to get people who really want to use the strengths here as well as doing their own thing – the resources of the Sanger will be thrown behind them. It’s a fantastic opportunity for them and for us."

See also

• The Human Genome Project: Information on the project and the key issues
• Understanding the genome: Article on the new five-year research programme

External links

• The Sanger Institute