The Nobel Prize in Chemistry 2014

I'm going to guess he means they work via chemistry and exploiting heat in the system ie brownian ratchets.

It's quite a vast topic. When you look at typical biochemistry text books, everything seems static. Even when something changes (e.g., some changes in the environment), some proteins are switched off, others switched on and the cell returns to a certain seemingly static state. What's missing in this picture are the incredible dynamics in the system. It is a truly complex dynamical system, constantly switching from one fix point to another. The rates of processes and the dynamic location of molecules plays a much more important role in the inner workings of a cell than was previously believed.

To be more specific: Self Organization Cells and organisms have incredibly detailed structures or spatial and temporal patterns on time and space scales far beyond typical biochemical reaction rates and the sizes of the molecules. These patterns are not created by someone or something; they emerge from the localized dynamic interplay between many same and different molecules - self organization. In a certain sense the cell and any organism is a dynamical system that self-organizes into intricate patterns, something that is mostly only appreciated by physicists working in biology, rarely by biologists themselves. This has consequences that are often still not appreciated. An example (hope I recall it all correctly, it's been a few years): I was working on so-called Src-family protein kinases (SFKs), proteins that phosphorylate other proteins and thereby change their conformation so that they themselves become activated. SFKs play a huge role in many different signal transduction pathways and therefore in many different diseases. Because of their importancy they are regulated/controlled on many different levels. One of them is that they are self-inhibiting: they bind intramolecularly to a phosphate group and thereby block its own activity. To become activated, they need to be dephosphorylated by some phosphatase and they need to be phosphorylated at another position by another SFK intermolecularly. In the standard biological treatment, it's all pretty simple: phosphatase dephosphorylates, SFK phosphorylates - done. However, as SFKs bind themselves, they block access to the site that the phosphatase wants to dephosphorylate - why could this system then be responsive to any changes, why doesn't it simply stay in this state forever?

Dynamics. SFKs most likely (that was more my hypothesis at that time, don't know what the situation is like now) constantly unbind and bind its inhibiting phosphate at a low rate. In its unbound state, the phosphatase can access the phosphate. As the active SFK in turn activates its own phosphatase (a feedback loop), more phosphatases are around, dephosphorylating more SFKs in their unbound conformation, leading to a mostly active population of SFKs. Now when you incorporate spatial aspects into this, you get yet another picture: as SFKs activate themselves constantly (via autophosphorylation), a simple accumulation of many SFKs in a certain part of the cell (e.g., the cell membrane) could be enough to move the whole system above an activation threshold, leading to a complete cell-wide SFK activation. This would not require any of the standard causes used to explain activations in biology. Hope I managed to get at least a little bit across of what I mean.

In a nutshell: for me, the Nobel Prize was awarded today to a novel experimental method that nicely shows that cells are no bag full of chemicals and should not be investigated and explained as such; the role of spatial and temporal patterns is much underappreciated still. Or something like that.

Here's a pretty nice simulation/explanation of what makes STED work [1]. There are similar competing technologies that do essentially the same thing in order to arrive at sub-difraction-limited images including STORM & Structured Illumination. Google around for STORM, STED and the prettiest pictures will come from 'cytoskeletal' features, though some really interesting nano-mater-scale studies have been conducted with respect to synapses, the nuclear pore, and a number of other sub-cellular structures that would have otherwise been extraordinarily difficult.

[1] http://microscopyu.com/tutorials/flash/superresolution/stedv...

The room in the picture is one of the short-term rooms used almost exclusively for visitors and conference attendees. Long-term on-campus townhouses and condos have nice modern designs but not that kind of view :)