Sara Courtneidge: swimming with Srcs

Sara Courtneidge has recently been appointed vice-president of research in the California-based biotechnology company, Sugen, Inc. Her pioneering research into how the Src tyrosine kinase is involved in cellular transformation has provided the basis for understanding how members of the src gene family act in normal signal transduction pathways. In her new position, Dr Courtneidge will be trying to identify components of signal transduction pathways as targets for pharmaceutical intervention. Dr Courtneidge’s career began when, at the age of eight, she announced that she was going to be a scientist. Thirteen years later, she obtained an Honours degree in Biochemistry at the University of Leeds and moved to the National Institute for Medical Research (NIMR) at Mill Hill, England for her doctoral studies. There, under the supervision of Mike Crumpton and John Skehel, she studied how cells infected with influenza virus are recognized and destroyed by cytotoxic T cells. During this time, Dr Courtneidge’s critical and analytical skills were sharpened by the continual barrage of questions on seminars and papers from John Skehel, who worked on the lab bench opposite hers. Throughout her postgraduate studies, Dr Skehel encouraged her to think about her future scientific direction, a process that resulted in her securing a postdoctoral research position in J. Michael Bishop’s lab at the University of California, San Francisco. Having only ever spoken to Dr Bishop on the telephone, Dr Courtneidge was initially overwhelmed on her arrival at the lab in San Francisco. The combined Bishop and Varmus laboratories were, at that time, beginning to identify the cellular genes that had been incorporated into RNA tumour viruses and which gave them the ability to transform cells. This was, and has continued to be, a large, energetic laboratory at the cutting edge of molecular biology research and Dr Courtneidge was the youngest and newest member. However, she soon adjusted to the dynamic environment and began her work on identifying the structural and functional domains of the transforming protein isolated from Rous sarcoma virus, pp60v-src, or Src. On her return to England, she was offered a junior staff position at NIMR where, together with Alan Smith, she demonstrated that the transforming protein of polyomavirus, middle T antigen, acquired its tyrosine kinase activity by association with the cellular homologue of pp60v-src. From this work, Dr Courtneidge was inspired to examine the normal role of the Src protein in cells and discovered that the cellular Src protein is, itself, negatively regulated by tyrosine phosphorylation. In the mid-1980s, Dr Courtneidge accepted an offer to join the European Molecular Biology Laboratories (EMBL) in Heidelberg, Germany. The organization of EMBL, with several, small interactive research groups and a multi-cultural composition, provided an exciting and stimulating backdrop for Dr Courtneidge to develop her research interests. During this time, a number of groups throughout the world began to identify other cellular tyrosine kinases that were related to, and shared certain domains with, the cellular Src protein. Dr Courtneidge’s laboratory demonstrated that these proteins were absolutely required for the normal control of cellular growth. She also showed that members of this family were components of normal signal transduction pathways, regulating the pathways by virtue of their kinase activity. This provided a valuable means for studying how cellular growth is regulated in normal cells and also how this regulation is disrupted in transformed cells. Despite having the rare privilege of an open-ended position at EMBL, Dr Courtneidge recently decided it was time for a new challenge. This came in the form of an offer to direct the research division of Sugen, Inc. There, her laboratory will be trying to identify components of signal transduction pathways which can act as new therapeutic targets for the treatment of diseases such as cancer. While there is no doubt that the application of her work to a commercial setting will be very challenging, Dr Courtneidge has successfully been swimming with Srcs for most of her research career and has always managed to tame them. Magazine 625