Giants in genomics: Allan Bradley

Allan Bradley received his BA, MA and PhD in genetics from the University of Cambridge. His final year undergraduate project in Martin Evans’ laboratory involved the isolation of embryonic stem (ES) cells from mouse embryos. He continued this work during his PhD, remaining in Martin’s laboratory, making the key observation that these embryonic stem cells could be transmitted through the germline of mice.

In 1984, following this discovery and supported by a postdoctoral fellowship from the Beit Memorial Trust, Allan started to develop a technology to target specific genes in embryonic stem cells. In 1986, Allan discovered that embryonic stem cells can be used to generate mice with mutations in specific genes, also known as knockout mice. This work was a significant contribution to the work of Martin Evans, who was awarded the Nobel Prize in Physiology or Medicine in 2007, along with Oliver Smithies and Mario Cappecchi.

Gene targeting technology was incredibly important for providing a key insight into the involvement of genes in cancer.

In 1987, Allan was recruited by Tom Caskey and moved to Houston, Texas to become an assistant professor at Baylor College of Medicine. Here, he continued the work he had started in Cambridge on gene targeting technology. This technology was incredibly important for providing a key insight into the involvement of genes in cancer, the repair of DNA and embryonic development. It led to the publication of over 150 research papers.

In 1994, at the age of 34, Allan was promoted to full Professor at Baylor and was also appointed as a Howard Hughes Medical Institute Investigator. At Baylor, his laboratory played a central part in developing the techniques, technology and tools for genetic manipulation in the mouse. In his role Allan set high academic standards. He led a number of committees and was actively involved in graduate and postdoctoral training and mentoring.

In 1995, Allan founded Lexicon Genetics Inc., and was actively engaged in commercialising the embryonic stem cell technology he had previously developed in the lab. A year later, his laboratory developed another technology known as array-based comparative genomic hybridisation (aCGH) which was later applied for pre and post-natal genetic diagnosis.

When Allan was appointed director of the Sanger Institute in 2000, it was not only a time full of promise, but also a time of uncertainty for genomics.

When Allan took over from John Sulston as director of the Sanger Institute in 2000, it was not only a time full of promise, but also a time of uncertainty for genomics. With the announcement of the draft sequence, there were a number of questions about what the Institute would do next and how the information from the sequence would be translated into useful science.

“The question was: how does an institute which, essentially, had just one project evolve a more holistic approach?” says Allan. “How do you add an academic dimension to a place that has been focused on the achievement of one major technical goal for so long?”

So, Allan’s first task was to set out a new strategic plan for the Sanger Institute and transform it from a centre sequencing genomes, to one focused on the biology of those sequences.

Allan was keen to direct the Institute with the genome sequences of organisms as a pivotal part of filling in the gaps in our knowledge of biology and disease. In addition to this, he wanted to maintain the open philosophy of the original Sanger Centre’s culture, as established by John Sulston, while also making the Institute an attractive place to do innovative science.

As a starting point, Allan set out to recruit a talented faculty of researchers, some of whom established and led large consortia projects such as the International Cancer Genome Consortium and 1000 Genomes Project. By doing this, Allan was investing in the next generation of scientists, allowing them to grow and develop into world leaders in their fields.

Allan remained director of the Institute for 10 years. During this time he oversaw the completion of Sanger’s contribution to the Human Genome Project and the completion of the first mouse, malaria and cancer genome sequences. But it wasn’t all about sequencing, as Allan was also involved in many functional studies. These included the European Conditional Mouse Mutagenesis Program (EUCOMM), an international collaboration to create lines of mice in which an existing gene has been inactivated, and the establishing of a major programme of malaria research at the Sanger Institute. Throughout his directorship, he continued to take an active role in the lab, leading a group focused on developing mouse models of cancer, genetic screens in mouse embryonic stem cells and, most recently, the genetic modification of human stem cells. The campus also underwent major infrastructure changes. The Morgan Building, hosts research labs, IT and the data centre, and the Research Support Facility, houses a state-of-the-art animal research facility. These were important additions to the Institute.

Allan has been described as a ‘true, scientific visionary’ who led the Sanger Institute into the ‘post-genomic era’.

Throughout his career Allan Bradley has played a huge role in developing animal models for use in scientific research. This has focused particularly on the mouse and has continued even after he stepped down from his position as director of the Sanger Institute. He has been described as a ‘true, scientific visionary’, who led the Sanger Institute into the ‘post-genomic era’. Under his directorship, the Sanger Institute published more than 3,000 scientific papers between 2005 and 2010, with an average of one publication each week in a major scientific journal.

He currently splits his time between Kymab Ltd as Chief Technical Officer and the Wellcome Trust Sanger Institute, where he is a senior group leader. He was elected a Fellow of the Royal Society in 2002.