Feedback

Jimi Hendrix.
Master of feedback, burner of guitars.

At six in the morning, on 18th August 1969, Jimi Hendrix took to the stage at the Woodstrock festival. In amongst his two and half hour set were many of his hallmarks - smashed guitars, fires, unpredictable guitar solos, playing behind the head and with teeth, and a new technique which Hendrix himself had invented.

Newspapers described his new effect as a protest against the Vietnam war because it sounded like "falling rockets". It was, simply, feedback.

Biologists (and Physicists) might qualify that a little - it was "positive" feedback. The vibrations from Jimi's guitar strings fed down into his guitar's pickups and across the stage in a wire. The sound was amplified and pumped back at the crowd. But it didn't end there.

Jimi turned to point his Fender at a wall of amplifiers so the sound caused new vibrations aross the strings. These fed back down through the guitar's pickups again, were amplified again, and spat back at his guitar again... The loop repeated, building and boosting until it reached a scream. Then, well... it was anyone's guess what Jimi would do next!

Positive feedback.
It happens in our cells as well.

In nature feedback is everywhere. 

Positive feedback loops happen in all of the cells in our body, and have done since the day we were born.

 

A protein called Cyclin B, for example, is boosted by positive feedback. As Cyclin B levels rise, they have a knock-on effect on another protein, Cdc25 which boosts Cyclin B even further. Just like Jimi with his Strat, biologists call this "amplification". Without amplification of Cyclin B our cells couldn't divide.

The natural world has also evolved forms of negative feedback, which has the opposite effect: instead of amplifying higher and higher it pushes back, reducing noise to silence or, in some cases, producing ellaborate cycles and patterns.

To see how, let's forget guitar heroes and cells for a moment and think about foxes and rabbits.

Rabbit and fox, prey and predator

In the wild, a thriving rabbit population naturally leads to a healthy surge in the population of foxes looking for an easy meal. The rabbit population inevitably falls, which leaves the fox population hungry so, after a delay, it too begins to fall. With fewer foxes around, the rabbits begin to multiply again...The two populations - predators and prey - are locked together, they rise and fall repeatedly. They oscillate.

Negative feedback.
Guess what? It happens in  our cells too.

Negative feedback loops are the driving force behind all sorts of biological oscillations - everything from seasonal changes to our heart beats to the hundreds of proteins wired together in our cells to control the response to diseases. (more about those in another post!)

On stage, Jimi Hendrix played around with negative feedback too. His wah-wah pedal used negative feedback to cancel-out some frequencies of sound whilst boosting others. Combining negative and positive feedbacks helped Jimi to define a new era of guitar playing.

It's no suprise that inside the cell, to achieve its incredible range of different functions, many sets of proteins are wired into positive and negative feedback loops which are also wired to each other! 

Jimi using feedback during "Star-spangled banner"

Woodstock festival, 1969

For more on biological cycles, have a look at this. I'll be writing on what oscillations actually do inside cells in a later post!

Reference (one of the earliest):

VOLTERRA, V. (1926). Fluctuations in the Abundance of a Species considered Mathematically Nature, 118 (2972), 558-560 DOI: 10.1038/118558a0

The explosive, moving, crushing, slightly depressing, exciting reality of the cell (and how it's a bit like a red Ferrari).

My first wheels.

My first experience of driving a car was totally reckless. At top speed I mounted the kerb, grinning at passers-by as I slammed into a wall. I then leapt out of the seat, vaulted the wall, and ran off in search of criminals.

Granted, I was pretending to be Magnum P.I at the time and had a top speed of how fast a 3 year-old can scoot along whilst sitting down. But the thought was there: this is easy, let’s open this baby up on a slope, see what she can do.

When I finally got behind the wheel (of a Ford Escort, not a Ferrari), some 15 years later, the reality came as quite a shock - there were gears, and brakes and stuff to check and top-up. So many things to remember when I just wanted to screech around the place - and this was all before I’d even looked under the bonnet/hood. But, like everyone else I learnt, because... well, that’s the reality if you want to drive.

The depressing reality of the car (but beautiful to some)

When I first looked down a microscope at some cells, I was similarly astonished. These cells weren't all the same shape or size, they weren't staying still, in fact they were twanging around the place. And inside? Inside it looked like complete chaos. 

The cell in front of me was a microscopic machine: millions of proteins crashing together and breaking apart; some were building the cell from within, or acting as scaffolding, or fighting infection, or making copies of DNA before ripping the enitre cell neatly in two every 24 hours.

The GCSE cell, simplified but still correct.
(Credit BBC Bytesize 2011)

Our cells are full of moving parts. And if we want to fix them when they go wrong, such as when a cell becomes cancerous, we first need to understand how they work - how all these parts are wired together. It's quite a daunting and slightly depressing challenge - how on earth do we go about it?

One way is to work on smaller pieces of the cell first. Just as a mechanic will work on the exhaust system, the electrical system and the cooling system of an engine, cell biologists might specialise in the p53 DNA damage system, the NF-kappaB sgnalling system or the cell cycle.

In the end, would-be cell biolgists face a choice - to look at the horrific, awe-inspiring complexity of the cell's wiring and either run screaming or accept that there's lots to see, roll up your sleeves and get your hands dirty!

The horrific, but beautifully complex, wiring of the cell.
Up to you... do you want to know more?
Download this poster as a PDF from Cell Signalling.

In future posts I'll tell you how scientists have looked under the cell's bonnet/hood, what they've found out about its systems and their wiring, and what the future might hold...