As a graduate student at Imperial Cancer Research Fund in London in the late 1980s, I worked on 'oncogene cooperation'. My graduate advisor, Hartmut Land, had shown that two different types of oncogenes, such as Ras and Myc, were needed to transform primary rodent fibroblasts into tumour-like fibroblasts. I made the intriguing observation that expression of oncogenic Ras by itself in primary Schwann cells inhibited proliferation, whereas Ras in combination with Myc or SV40 large T induced transformation. This finding led me to collaborate with Hugh Paterson from Chris Marshall's laboratory in the Institute for Cancer Research. Hugh had mastered the fine art of microinjecting purified proteins into cells, and when he injected my Schwann cells with oncogenic Ras protein, we found that Ras alone inhibited DNA synthesis. The power of microinjection as a tool to study immediate cellular responses to proteins struck me at the time, but after I completed my PhD I wanted to work in the US, and so moved to Boston armed with an EMBO postdoctoral fellowship. However, I soon realised that the research I was doing was not suited to me. When I discovered that Alan Hall, who worked with Chris Marshall on Ras, was advertising a postdoctoral position, I went for an interview and ended up taking the job and returning to London.
Alan Hall's and Chris Marshall's offices and labs were right next to each other, sharing equipment and Hugh's expertise, and providing a fantastic environment in which to work as a postdoctoral fellow. I considered initially working on neurofibromatosis 1, which had just been identified as a GTPase-activating protein for Ras. This seemed to be an excellent link to my graduate Ras and Schwann cell days, as neurofibromatosis is a Schwann cell cancer. I had even been to a neurofibromatosis workshop where I had presented my data on Ras in Schwann cells. My ideas changed, however, after a few trips to the library. Alan and Hugh had just published a paper showing that a recently identified relative of Ras called RhoA induced dramatic changes to cell shape. After reading papers such as Dafna Bar-Sagi's report that injection of oncogenic Ras stimulated membrane ruffling, and studies describing the effects of growth factors on the actin cytoskeleton, I became convinced that the link between the actin cytoskeleton and Ras and Rho proteins was the area I wanted to pursue, and so I asked Hugh to teach me how to microinject cells.
This is a preview of subscription content, access via your institution
