Monday, 27 June 2016

Molecule of the Month July 2016: Bacteriophage T4 coming into land!

Bacteriophage, or more commonly 'phage for short, is the name given to viruses that infect bacteria (you can see the schematic diagram of phage T4 on the left). You will have come across the suffix phage in oesophagus or as a prefix in Phagocytosis: it has Greek origins and means to eat. I first came across bacteriophage in 1977 during an undergraduate lecture by Dr. Bernard Fry at Sheffield. I was immediately hooked! Here was one of the first scientific conundrums I faced: are bacteriophage dead or alive? Is a biological "system" that requires the "machinery" of a bacterial host to replicate (phage, incidentally outnumber most species on the planet), a living organism or an inert molecule? For me it sparked an interest in the origin of life, and it also sparked another interest, in the area molecular structure and function. Our appetites (well those of us who found these lectures fascinating) were whetted further by what felt at the time to be powerful Electron Microscopy (EM) images. Fifty years on from these classic experiments, in the light of the marvellous structural biology images of multi-subunit enzymes such as the ribosome, with which we have become so familiar; the early EMs appear, well, maybe a little dated?

As me and my classmates passed through the various Biochemistry lecture courses in metabolism and enzymology, we finally caught up with these strange hybrids between living organisms and molecular assemblies in crystallography lectures, when Professor Pauline Harrison showed us images of the plant virus: Tobacco Mosaic Virus (RHS). It was clear that phage and viruses would hold a beauty that just needed time and patience, and the development of better methods of sample preparation, data collection and analysis, for high resolution structures to emerge. Well those methods  have finally arrived and the technique of cryo EM is now set to provide us with molecular details of these macromolecular machines. I shall provide a small amount of background information to help provide a context to the work.