Toxic mushrooms

If you have a problem, no matter how large or small, Current Biology's 'agony aunt' Amber can help. Dear Amber, I pioneered a wonderful, elegant technique that everyone used, and for a while they all looked up to me. Now, a new method has superseded mine, and I'm no longer considered important. What can I do? Dear Technical, Rejoice, science has progressed. It's left you behind, and that's too bad, but truth, like fire, is a hard master. If you wanted a profession in which you could be sure of being a little tin god forever, why didn't you go into medicine? Amber Dear Amber, I've been a dedicated and hard-working post-doc in a molecular biology lab for 15 years, but there just aren't any tenured jobs to be found. What can I do? Dear Sheepish, I assume you've already considered the obvious alternative career choices being pursued by many of your peers — the biotechnology industry, patent law, and business, for example. It's hard to give you sound career advice on the basis of so little information, but you are obviously something of a masochist to have stayed a post-doc for so long. Have you considered applying to be Bill Clinton's press secretary? Amber The mushroom-shaped structure shown below is the damaging membrane pore complex formed by a bacterial toxin: the Staphylococcus aureus α-hemolysin. S. aureus is a human pathogen that is involved in a range of diseases, from skin inflammations to septicaemia. Much of its pathogenic effect is due to cell lysis, caused by the α-hemolysin toxin. Lysis of cells provides nutrients, especially iron, for bacterial proliferation, and may facilitate invasion into neighbouring tissues. The toxin is secreted as a monomer that binds to the surface of eukaryotic cells, including erythrocytes, platelets, monocytes, lymphocytes and endothelial cells. Once bound to the cell membrane, the α-hemolysin monomers assemble to form pore complexes, which penetrate the lipid bilayer. Each pore complex is composed of seven subunits — shown in different colours in the ribbon representation below — each of which contributes two β sheets to form a channel through the membrane. With pores puncturing the cell membrane like the holes in a sieve, water can rush into the cell, causing swelling and, eventually, lysis.