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In 1945, Max Delbrück arranged the first Phage Course, held at the Cold Spring Harbor Laboratory, New York, to guide research in phage biology. Very many of the microbial scientists that are now hallowed names attended the course over the years, including Benzer and Stahl, and some are remembered in the names of the buildings. Indeed, the course itself is held in the Delbrück Laboratory. The course runs today with similar but broader aims, under the guise of Advanced Bacterial Genetics. I was fortunate enough to be selected to attend this highly-regarded three-week practical course this Summer, under the instruction of Professors John Kirby, Sue Lovett and Anca Segall.
Many of the experiments conducted on this intimate course (we were just 16 students) were part of real research projects from our instructors’ labs and not merely exercises that countless generations of hopefuls had worked through. We didn’t know what results we might record; this, we were told, was what put the “Advanced” in “Advanced Bacterial Genetics”. It provided the motivational edge to get us out of bed in the mornings when we’d been in the lab past midnight the night before. Indeed, we did isolate mutants and make observations that I look forward to following up in due course. But, of course, by no means were all the experiments plain sailing! One experiment proved to be so recalcitrant that “Come on and rescue me” was adopted as the course anthem.
With about 20 experiments running concurrently, there was a lot to learn. A wide range of mutagenesis and selection protocols were presented, useful to expose any number of biological truths. Some were simple but previously unknown to me, such as passaging a plasmid through a mutator strain to obtain random point mutations; others were more subtle, such as selecting pools of mutants for modulated (rather than all-or-nothing) survival phenotypes. The use of trusty reporter strains – a mainstay of bacteriology for generations of researchers – featured highly. However, without doubt the most technically challenging task was streaking out 8 mutants to single colonies on semi-solid agar! There were also no shortage of time-saving hints and tips, for which we were all grateful, for example, use of the “pronger” for spotting multiple bacterial cultures onto agar plates at once; the rapid MUG assay for B-galactosidase activity; and the use of 96-well plates for serially diluting cultures on a large scale.
Perhaps some of these techniques aren’t fundamentally different from those taught years ago, but the lab was equipped with state-of-the-art equipment too. For example, a variety of quantitative PCR approaches were presented and utilised. A high-end microscope was on loan from Zeiss, and enabled us to study predation in Myxococcus xanthus, and to try our hand at immunofluorescence microscopy to study subcellular localization of chemoreceptors. In addition, there was plenty of theory to complement the practical aspect of the course. The instructors’ particular fields of interest were taught to us as background to the experiments. Even more bacteriology was taught in the seminars, held daily, and given by eminent scientists such as Kelly Hughes, who kindly reduced the irreducible complexity of the bacterial flagellum for us with a talk entitled “Life without a hypothesis. ” Stanley Maloy countered this philosophy with his talk, “Life with a hypothesis,” to explain host specificity in Salmonella.
The instructors were, unexpectedly, as good at entertaining as they were at teaching. Apart from the general feel good atmosphere in the lab, we grateful course participants were treated to a sushi night at a local prized restaurant, as well as pizza, and Sue’s notorious “Happy Punch”. Not for the faint of heart was the sailing trip that John had organised – we were able to help raise the sails, but ordered to hold tight when even the crew seemed uncertain that we could navigate a harbour tightly packed with exclusive yachts and sailing boats in the unseasonably strong winds.
Whether or not my research career will equal those of Luria and Delbrück, the Advanced Bacterial Genetics course and Cold Spring Harbor Laboratory have played an important formative role in my career; for that, I’m as indebted to my contemporary coursemates and instructors as I am to those venerated figures of the past. I am grateful to funds awarded by BSPP, Boehringer Ingelheim Fonds and Trinity College, Cambridge, for allowing me the chance to participate in this hugely worthwhile experience.
Terry John Evans George Salmond’s Laboratory, University of Cambridge