Resurrection: Halloween, spooky proteins and the return of ClearSci

It’s Halloween night and a dark shape is moving towards you through the ether of the information superhighway. Surrounded by the blackness you feel something closing in, disturbing the thick layers of accumulated dust. Just as you’re about to start screaming in terror… IT’S ME!!! Lights on, and by gosh it’s a mess in here, I don’t remember putting all of these spiders up for Halloween. Eww! Eww, eww, they’re real. I’m really going to need to spend some time cleaning all of this up…I’ll deal with that later.

Halloween revival.

So, if you’re here that means you’ve been on the look-out for more of my slightly eclectic and sporadic brand of science writing and I will try not to disappoint this time. Just so we’re all caught up, no I’m not dead and neither is this blog, it just went into reverse-hibernation over the summer (that’s called aestivation, if you’re interested). Also, neither of us has been temporarily reanimated for Halloween, this will hopefully be working its way back into my normal routine.

Summer was great! Although crazy, so I didn’t have much writing time (poor excuse I know). I joined the college graduate committee so I’ve spent a lot of time planning and organising events for our new freshers and negotiating college politics. I also finished the third rotation for my first year (currently in editing for the Wellcome Trust), selected my PhD project and wrote the full project proposal (I’m back with the second lab, playing with fission yeast genes). All of that earned me an MPhil which I will be collecting sometime in the new year.

Things have been busy with BlueSci, we’ve organised a whole new set of events and are working hard to collaborate with other science societies around Cambridge. We’ve also got a new radio show and after a very successful Issue 22 (the current issue), planning is already underway for the next one (arriving in January).

Oh, also I was at Science Online London, which was an excellent chance to see all the best of the latest advances in sharing science globally and I went on the Science on Air course at Imperial College London, getting the chance to develop skills in both Radio and Film recording. Oh yes and, in case they’re stalking me (which I’m lead to believe they do) I’m now involved in supervising second year (Part 1B) undergraduate students in Biochemistry, which I’ve been hugely excited about for years.

I finally moved out of college accommodation too, now living in a real house (shared, rental) with some awesome housemates and enjoying the luxuries of a shared living space complete with such novelties as a sofa and a huge TV, which have had a terrible effect on my productivity.

Getting in the spirit with the Halloween proteins

Anyway, you didn’t come to hear me talk about myself, I’ve done too much of that in previous posts, and I’m generally not very interesting anyway. So, in keeping with the festive Halloween theme, and going back to my biochemical roots for this ghoulish rebirth of ClearSci, we’re going to explore the deep, dark horrors of Spooooooky proteins! Wooooooo! (Scared myself there a little bit…)

A lot of cell biology/biochemistry is about finding new proteins and figuring out what they do and how they interact with other proteins to form the functional networks needed to keep a cell alive and active. Naming of new proteins can be quite a complex process. Most proteins are now identified first from the genes that make them in the genome, they are then usually given a systematic name which are often dull and impossible to remember e.g. Cyp315a1 or CG3973. Proteins are often assigned a more memorable name once they have been closely studied. This name usually relates to the effects of losing that protein. This naming convention has always been especially common, and humorous, in the Drosophila (fruit fly) field. The proteins I want to introduce today have all been given common names with a Halloween theme and I will attempt to explain why.

First, there are the Halloween proteins, these are an actual family of proteins active in developing insect species. When the Halloween proteins lose function the exoskeleton (the hard structure that surrounds, supports and protects an insect giving it a shape and allowing it to move) does not form properly and embryos die before they are able to hatch from the egg. The lack of an exoskeleton means that these insects are very soft and lack proper structure, in addition to the fact that they die very quickly, they have been compared to ghosts. As such the seven Halloween proteins in flies have been dubbed Spook (Spo), Spookier (Spok), Spookiest (Spot), Phantom (Phm), Disembodied (Dib), Shadow (Sad) and Shade (Shd).

The Halloween proteins are all involved in the production of a signalling molecule called 20-hydroxyecdysone (20E) which controls when insects undergo moulting. When an insect moults it sheds its current exoskeleton and grows a new larger one. The Halloween proteins are all classified as cytochrome P450 enzymes, which are involved in the production of steroid signals (20E, testosterone, oestrogen) from cholesterol, amongst many other highly diverse functions. Once 20E reaches a high enough level within an insect it can activate signalling inside cells, which affect gene activity. The activation of new genes initiates the moulting process.

The Grim Reaper, here to kill cells.

As you might expect, proteins involved in causing cell death have also acquired a chilling selection of names. First up, the announcers of death Grim and Reaper (and the related protein, Diablo). All multicellular organisms have ways of intentionally initiating cell death, helping to control proper growth and body shape and preventing development of cancers.

The main process of planned cell death is called apoptosis and involves a systematic shutting down and destruction of several key systems within a cell. Grim, Reaper and Diablo are all IAP antagonists. IAP (inhibitor of apoptosis) blocks the activity of cell death enzymes, which can breakdown the structures within a cell. Grim, Reaper, Diablo and others prevent IAP from working and allow cell death to occur. Grim and Reaper activity also prevents the cell from generating energy by shutting down mitochondria, the structures responsible for providing usable energy in a cell. Later studies showed that other proteins are needed to allow Reaper to silence IAPs, these came to be known as Scythe and Sickle.

I'm serious, does anyone remember Casper?

The cell death enzymes that are so closely regulated by Grim and Reaper, which cause a catastrophic breakdown of cell processes and cause rapid cellular collapse all belong to the Caspase protein family. Does anyone even remember Casper the friendly ghost anymore? Caspases are proteins which destroy other proteins (Proteases) primarily they bring about the destruction of the genome and of the mitochondrial energy supply. This is an extremely rapid cascade reaction, primarily involving two groups. Initiator caspases are activated first by signals from outside the cell. This leads to activation of the executioner caspases which propagate cell death.

I’ll take my final example from the plant kingdom. Loss of this protein causes plants to have exceptionally hairy roots. In plant roots, certain cells produce very long thin root hair structures, which consist entirely of just one cell. This protein acts to prevent the development of root hairs in most root cells. When it is lost, almost all root cells produce hairs. As such, the protein has been dubbed Werewolf (Wer) and it limits the activity of genes which direct hair formation.

There are other proteins I could talk about, but you all have better things to do on Halloween. Other terrifying proteins lurking in the dark include Mummy, which holds cells together and Drop dead which prevents brain deterioration. In times of dire need, at least you can call upon the Exocyst, a series of proteins which aid the transportation of proteins out of cells.

Well that’s it from me. And that’s almost it for Halloween too. See you back here very soon, for some less spine chilling investigations.